Green Chemistry Using Bismuth Compounds: Bismuth(III

Illinois Wesleyan University

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Green Chemistry Using Bismuth Compounds: Bismuth(III) Triflate Green Chemistry Using Bismuth Compounds: Bismuth(III) Triflate

Catalyzed Allylation of Cyclic Acetals Catalyzed Allylation of Cyclic Acetals

Matthew J. Spafford, '09 Illinois Wesleyan University

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Green Chemistry Using Bismuth Compounds: Bismuth(III) Triflate Catalyzed Allylation of Cyclic

Acetals

Matthew J. Spafford

Advisor: Dr. Ram Mohan

Research Honors Senior Thesis

Illinois Wesleyan University

Spring 2009

Approval Page i

Green Chemistry Using Bismuth Compounds: Bismuth(III) Triflate Catalyzed Allylation of Cyclic Acetals

By

Matthew 1. Spafford

A PAPER SUBMITTED AS PART OF THE REQUIREMENT FOR RESEARCH HONORS IN CHEMISTRY

Approved:

Ram S. Mohan, Ph. D. , Research Advisor !

Brian B. Brennan, Ph. D.

"�a � Rebecca Roesner, Ph. D.

Nathan Frank, Ph. D.

Illinois Wesleyan University, April 20, 2009

Acknowledgements

I would first like to thank my research advisor and friend, Dr. Ram Mohan, for all his

support and encouragement over the past years. He has instilled a passion for chemistry in me

through his teaching and for that, I am very much indebted to him. His guidance and support has

been instrumental in shaping me as a scientist. I am also very grateful for the countless hours he

has spent on my behalf, without which this dissertation would not have been possible.

I would also like to thank Dr. Brian Brennan, Dr. Rebecca Roesner, and Dr. Nathan

Frank for serving on my thesis committee.

A special thanks is in order for the all members of the research group over the past years:

Aaron Bailey and Erin Anderson for their especial patiertce while training me as a Sophomore;

Scott Krabbe for his synthesis of dioxanes and his wonderful country music collection; Dr.

Eeshwar Begari for his early work on the allylation of dioxanes; Jay Christensen, Matthew

Huddle, and Josh Lacey for their work on the allylation of dioxolanes; Pash DeVore, JP Carolan,

Kendall Tasche, Jason Bothwell, Dan Podgorski, Maggie Olsen, Long Le, Jamie Rogers, Herbie

Yung, Justin Emat, Ashvin Bam, Ann Palma, Veronica Angeles, Paul Sierszulski, and Phil

Lazzara for making time in lab over the past years such a great time.

I also need to acknowledge Cindy Honegger for all of her help in the stockroom over the past

two years. None of this work would have been possible if not for her assistance.

11

The Twelve Principles of Green Chemistry

1. Prevention: It is better to prevent waste than to treat or clean up waste after it has been created.

2. Atom Economy: Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.

3. Less Hazardous Chemical Syntheses: Wherever practicable, synthetic methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment.

4. Designing Safer Chemicals: Chemical products should be designed to effect their desired function while minimizing their toxicity.

5. Safer Solvents and Auxiliaries: The use of auxiliary substances (e.g., solvents, separation agents, etc.) should be made unnecessary wherever possible and innocuous when used.

6. Design for Energy Efficiency: Energy requirements of chemical processes should be recognized for their environmental and economic impacts and should be minimized. If possible, synthetic methods should be conducted at ambient temperature and pressure.

7. Use of Renewable Feedstocks: A raw material or feedstock should be renewable rather than depleting whenever technically and economically practicable.

8. Reduce Derivatives: Unnecessary derivatization (use of blocking groups, protection/deprotection, temporary modification of physical/chemical processes) should be minimized or avoided if possible, because such steps require additional reagents and can generate waste.

9. Catalysis: Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.

10. Design for Degradation: Chemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment.

11. Real-time analysis for Pollution Prevention: Analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control

111

prior to the formation of hazardous substances.

12. Inherently Safer Chemistry for Accident Prevention: Substances and the form of a substance used in a chemical process should be chosen to minimize the potential for chemical accidents, including releases, explosions, and fires.

Anastas, P . T.; Warner, J. C. Green Chemistry, Theory and Practice. Oxford University Press, New York, 1998, 30.

IV

Abstract

x�) R1.-lX n

X=O, S n = 1 , 2

Bi(OTfh (2.0 mol %)

�SiMe3 ( 1 .7 eq)

Cyclic acetals (dioxolanes, dioxanes, and dithianes) are common protecting groups in

organic synthesis but they can also be converted to other useful functional groups. A

bismuth(III) triflate-catalyzed multi component reaction involving the allylation of cyclic acetals

followed by in situ derivatization with acid anhydrides to generate highly functionalized esters

and thioesters has been developed under solvent-free conditions. Most reagents used to date for

the allylation of cyclic acetals are highly corrosive or toxic and are often required in

stoichiometric amounts. In contrast, the use of a relatively non-toxic and non-corrosive

bismuth(III) based catalyst makes this methodology benign and attractive.

v

Table of Contents

I . Introduction.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

A. Green Chemistry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

B. Bismuth Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

C. Literature Review: Allylation of Acetals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1

II. Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

A. Bismuth(III) Triflate Catalyzed Allylation of 1 ,3-Dioxolanes . . . . . . . . . . . . . . . . . . . . . 32

B. Mechanistic Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 7

C . Bismuth(III) Triflate Catalyzed Allylation of 1 ,3-Dioxanes . . . . . . . . . . . . . . . . . . . . . . . . 39

D. Bismuth(III) Triflate Catalyzed Allylation of 1 ,3-Dithianes . . . . . . . . . . . . . . . . . . . . . . . 4 1

III. Experimental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

A. General Experimental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

B. Bismuth(III) Triflate Catalyzed Allylation of 1 ,3-Dioxolanes . . . . . . . . . . . . . . . . . . 46

C. Bismuth(III) Triflate Catalyzed Allylation of5,5-Dimethyl- 1 ,3 -Dioxanes . . . . . 53

D. Bismuth(III) Triflate Catalyzed Allylation of 1 ,3-Dithianes . . . . . . . . . . . . . . . . . . . . . . 56

IV. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...... 63

V. Appendix: Spectral Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

VI.

VB

I. Introduction

A. Green Chemistry

The contributions ofthe phannaceutical industry, especially via synthetic organic

chemistry, to medicine have significantly improved the quality and length of human life. The

synthesis and commercial development of countless compounds now allow for the treatment of

diseases that have otherwise overwhelmed mankind. Over the past century, the discovery of

antibiotics and new medicines has contributed to prolonging the average human life span by

nearly thirty years.! The development of new fertilizers and pesticides has allowed for more

bountiful harvests. Despite the vast achievements of the chemical industry, the massive

amounts of hazardous waste produced cannot be ignored, especially when considering current

environmental issues and the hazards presented to human health. For example, in 1 984 a Union

Carbide pesticide plant in Bhopal, India released 42 tons of methyl isocyanate? Nearly 1 5,000

people have lost their lives as result of this toxic gas leak and many others have suffered health

problems due to exposure. Environmental drinking water contamination has also been a major

issue in the aftermath of the disaster.

The United States Congress has passed many laws to help reduce the amount of chemical

waste released into the environment. The most significant of these is the "Pollution Prevention

Act" (PP A) passed in 1 990.3 The PP A provides guidelines and laws on pollution prevention

through the proper use and disposal of chemicals. Also, source reduction and prevention have

been stressed in this legislation. The government tracks the production and release of toxic

chemical waste in the Toxic Release Inventory (TRI).4 In 2006, the TRI indicated that the

chemical industry ranks third in the amount of waste released by sector (figure 1 . 1 ) . The only

1

industries that produce and release more waste are the relatively large metal mining and

electricity sectors.

Figure 1.1: 2006 TID Total Disposal or Release of Waste by Industry4

Hazardous Waste 5%

Paper 5%

Food

Therefore, chemists need to be more concerned with pollution in terms of hazardous

waste being released into the environment. This has prompted synthetic organic chemists to

consider developing environmentally friendly chemistry or Green Chemistry. Green Chemistry

involves the design of chemical syntheses and processes that are more environmentally friendly,

reduce waste production, and avoid use of toxic reagents.2 The main goal of green chemistry is

to minimize the use of toxic chemicals by finding safe, effective alternatives. This type of

developmental strategy is an efficient way to reduce the chemical waste associated with a

synthesis. Also, avoiding the use of toxic and corrosive reagents makes synthesis much safer for

the chemists involved. The risk associated with the use of a chemical can be expressed as a

function of both hazard and exposure (eq. 1 . 1 )?

2

Equation 1.1

Risk = f [hazard, exposure]

Past strategies of reducing risk have involved limiting exposure to dangerous chemicals

by taking safety precautions and exercising especial care when handling reagents. This strategy

can be an effective way of increasing safety if exposure can truly be limited. However, due to

human error and faults in protective laboratory equipment, exposure control measures often fail.

Therefore, the Green Chemistry approach is to lower hazards by using inherently less toxic or

non-toxic reagents. This reduces risk associated with syntheses and reduces hazardous waste

overall. This concept can be accomplished through the practice of Green Chemistry where

information about toxicity of chemicals is utilized to lower hazard and reduce waste. This has

particular relevance to synthetic organic chemistry, a field in which many toxic, corrosive and

difficult to dispose of chemicals continue to be used in large quantities.

One concept that can be used to reduce the amount of waste associated with a chemical

synthesis is atom economy. Atom economy is a measure of the percent by mass of reactants that

end up in the desired product, and hence, is a good indication of the amount of waste material

associated with a process. The solvents and catalysts necessary for a synthesis are not

considered. This concept was introduced by Trost in 1 99 1 .5

Equation 1.2

A E Molecular Weight of desired product 1 0 Of tom conomy = x 070

Molecular Weight of all reactants

Many synthetic methods currently used yield byproducts that increase the amount of

waste associated with a synthesis. Also, if the byproducts are toxic this makes waste disposal

3

more difficult and costly. The Wittig synthesis of alkenes produces one equivalent of

triphenylphosphine oxide as a byproduct for every equivalent of alkene formed (scheme 1 . 1 ).

Scheme 1.1

o A +

o II

+ Ph/�'Ph Ph

In contrast to the Wittig reaction, a classic example of an atom-economic reaction is the Diels-

Alder cycloaddition. All of the atoms present in the diene and dienophile are present in the final

cyclized product. Thus, the only chemical waste involved with this synthesis comes from any

necessary solvents or catalysts (scheme 1 .2).

Scheme 1.2

R (j heat

The design of atom-economic processes allows for reduction of the amount of raw materials

needed and a decrease in waste generated. Thus, designing syntheses with this principal in mind

could drastically reduce the amount of waste produced by the chemical industry while also

reducing costs.

The concept of E (environmental) factor was introduced by Roger Sheldon in 1 992 to evaluate

the environmental impact of chemical processes.6a The E factor is defined in terms of the

amount waste associated with a process and the amount of desired product produced (eq. 1 .3).

4

Equation 1.3

E fi mass oj waste produced

actor = __ ---"-__ ----0... ___ _

mass of product produced

The E factor can be determined for either an individual chemical process or an entire

industrial sector. Sheldon determined the E factors for a number of different chemical industries

(table 1 . 1 ). He found that the E factors associated with fine chemical and pharmaceutical

synthesis were relatively high when compared with more efficient industries, such as oil refining

and bulk chemical synthesis. Production of waste on such a grand scale poses a major

environmental concern and also hurts the cost effectiveness of numerous commercial processes.

Table 1.1: E Factors of Various Chemical Industries

Industry Sector Product produced (Tons) E Factor (kg waste/kg product)

Oil refining 1 06_ 108 < 0 . 1

Bulk chemicals 1 04_ 106 < 1 - 5

Fine chemicals 1 02 _ 104 5 - 50

Pharmaceuticals 1 0- 1 03 25 - 1 00

The importance of considering E factors and other Green Chemistry metrics becomes

readily apparent when considering synthetic processes that generate large amounts of waste. In

the early 1 980s, Oce Andeno closed a plant responsible for the synthesis ofphloroglucino1.6b

Phloroglucinol is used as a raw material for the synthesis of explosives and pharmaceuticals.

Closure of the plant was necessary because the cost of disposing of the waste associated with the

synthesis was approaching the profits associated with the sale of phloroglucinol. The synthetic

strategy employed at Oce Andeno involved the oxidation of 2,4,6-trinitrotoluene (TNT) with

5

potassium dichromate in fuming sulfuric acid6c (scheme 1 .3). This was followed by reduction of

the nitro substituents with iron and hydrochloric acid and an in situ decarboxylation. Heating an

acidic solution of the resulting 1 ,3,5-triaminobenzene yielded phloroglucinol.

Scheme 1.3

CH3 C02H

02N'Q'N02 K2Cr207 02N'Q'N02

Fe/ HCI 10 )110 10 )110

H2S04/ S03 N02

- CO2 N02

2,4,6-trinitrotoluene

H2NyNH2 aq. HCI

HOyOH

10 10 )110

NH2 Heat OH

phloroglucinol

The E factor for this process was determined by Sheldon to be 40. Thus, for every kg of

phloroglucinol produced, 40 kg of solid waste containing Cr2(S04h FeCh, KHS04, and NH4Cl

was generated. The cost associated with the disposal of this waste made the process impractical

and resulted in the eventual closing of the Oce Andeno plant.

Though Sheldon's E factor is a good indication of the relative amount of waste produced

by a given process or industry, the nature of the waste produced should also be taken into

account when evaluating synthetic viability. A kilogram of sodium chloride or a similarly

benign salt is not equivalent to a kilogram of a toxic compound such as a tin salt when

considering the environmental implications of chemical waste disposal. All of these factors

should be considered collectively when designing Green Chemistry processes.

6

The approach to environmentally friendly chemistry in our laboratory utilizes non-toxic

reagents that are highly catalytic in nature. It is in this context that bismuth compounds are very

attractive as catalysts and reagents in organic synthesis.

B. Bismuth Compounds

Bismuth, the 83rd element in the periodic table, has a natural abundance of 0.008 ppm in

the Earth's crust and 0.0002 ppm in sea water.7 It is a soft, crystalline metal with a whitish-pink

hue. Bismuth is the heaviest stable element and the most diamagnetic element known.

Bismuth is a remarkable element because despite its proximity on the periodic table to

toxic heavy metals such as lead and antimony, it is relative non-toxic. Due to their non-toxicity,

bismuth compounds have found numerous applications in cosmetics and medicine. For example,

the active ingredient in the anti-diarrheal medication Pepto-Bismol™ is bismuth subsalicylate

(figure 1.2). Bismuth sub citrate is the only compound known to be active against Helicobacter

pylori, a bacterium that cause ulcers.8 Bismuth sub nitrate is used in medicine as a wound

dressing and as a component in ointment for inflamed skin. Cosmetically, bismuth oxychloride

is used to impart a shimmering effect to various makeup products. Bismuth is an

environmentally friendly alternative to lead as the main component of shotgun cartridges used

for waterfowl hunting.

Figure 1.2

o �9 VO .. Bi

'OH

Bismuth Subsalicylate

7

With increasing focus on developing environmentally friendly synthesis methods,

bismuth compounds have also been used as catalysts in synthetic organic chemistry. Bismuth

compounds have several attractive features in this respect.

There is no evidence to date to suggest that bismuth compounds are carcinogenic or

mutagenic.9 The remarkable non-toxicity of bismuth compounds has earned bismuth the

distinction of a "Green" element. IO This non-toxicity is primarily due to their insolubility in

neutral aqueous solutions such as biological fluids. Bismuth compounds are poorly soluble in

the blood plasma and are readily excreted via the urinary tract. The non-toxicity of bismuth's

compounds is evident from a comparison of LD50 values for a range of common Lewis acids

(table 1 .2). As can be seen from table 1 .2, most bismuth compounds are even less toxic than

sodium chloride. Even organobismuth compounds such as triphenylbismuthine are remarkably

non-toxic.

Table 1.2: LDso Values of Bismuth Compounds and Comparable SaltslO

Compound LDso (glKg) Species and Route

Sodium Chloride, NaCl 3 . 8 Rat, Oral

Bismuth oxide, Bh03 5.0 Rat, Oral

Bismuth nitrate, Bi(N03k5H2O 4.4 Rat, Oral

Bismuth oxychloride, BiOCl 22 Rat, Oral

Triphenylbismuthine, Ph3Bi 1 80 Dog, Oral

Mercury chloride, HgCh 0.001 Rat, Oral

Cerium chloride, CeCh 2 . 1 Rat, Oral

Indium chloride, InCh 1 . 1 Rat, Oral

Samarium chloride, SmCh 2.9 Rat, Oral

Scandium chloride, ScCb 3 .9 Rat, Oral

Ytterbium chloride, YbCh 4.8 Rat, Oral

8

Despite the fact that bismuth is not common in the Earth's crust, bismuth compounds are

relatively inexpensive. This is because bismuth is a byproduct of lead, copper and tin refining.

Many bismuth(III) compounds are commercially available at a low cost (table 1 .3), which makes

bismuth compounds even more attractive as potential catalysts.

Table 1.3: Availability of Bismuth(III) Compounds and Comparable Lewis Acidsa

Compound Cost/g ($) Cost/mol ($) Bismuth chloride, BiCh 2.25 7 1 1

Bismuth nitrate, Bi(N03k5H20 0.32 1 53

Bismuth oxide, Bh03 0.49 228

Bismuth Acetate, Bi(C2H302)3 3 1097

Bismuth trifiuoromethanesulfonate, Bi(OTf)3 1 0.60 6960

Scandium trifiuoromethanesulfonate, SC(OTf)3 37 17,820

Ytterbium trifluoromethanesulfonate, Yb(OTf)3 36 22,390

Trimethylsilyltrifiate, TMSOTf 1.70 378

Titanium tetrachloride, TiCl4 0.05 9.96 aSigma-Aldrich.com

Although the hydrolysis of Bi(III) salts in water has been reported (this is discussed in

more detail later, see scheme 1 .36), bismuth compounds are relatively stable and tolerate small

amounts of air and moisture. This contrasts sharply with moisture-sensitive Lewis acid reagents

and catalysts, such as BF3·Et20 and TiC14, that must be handled under an inert atmosphere to

ensure safety and viability of the reagent.

The electron configuration of bismuth is [Xe]4/45io6i6p3 . On account of weak

shielding by the 4f electrons (Lanthanide contraction) bismuth(III) compounds exhibit Lewis

9

acidity. Thus, bismuth(III) compounds can be utilized as potential Lewis acidic catalysts for

organic synthesis.

Bismuth can also exist in the +5 oxidation state. Organobismuth compounds with

bismuth in the +5 oxidation state are known and have been applied in organic synthesis. II

Bismuth(V) compounds are commonly employed as oxidizing agents. Sodium bismuthate has

been used for the benzylic oxidation of aromatic compounds 12 (scheme 1.4).

Scheme 1.4

HOAc, Acetone, H20

Triphenylbismuth(V) dichloride has been employed as an oxidizing agent for a variety of

functionalities, including the oxidative phenylation ofphenolsl 3 (scheme 1.5).

Scheme 1.5

OH

6 R

R = electron donating

Applications of Bismuth(III) Compounds as Catalysts in Organic Synthesis

A variety ofbismuth(III) compounds have been used as Lewis acid catalysts for synthetic

transformations. 14 Bismuth(III) chloride is one of the most thoroughly investigated bismuth-

based Lewis acids. The Knoevenage1 condensationl5 (scheme 1.6), Reformatsky reactionl 6

(scheme 1.7), Die1s-Alder cyclization1 7, Mukaiyama-aldol reactionl 8 (scheme 1.8), deprotection

10

of acetals1 9 (scheme 1.9), and the allylation of acid chlorides20 (scheme 1.10) and aldehydes2 1

(scheme 1.11) have all been reported with BiCh as the catalyst.

Scheme 1.6

Scheme 1.7

Scheme 1.8

Scheme 1.9

Scheme 1.10

BiCI3 ( 1 0.0 mol %) +

R2 = CN, COOEt, CONH2, COCH3 R3 = CN, COOEt

o

Ph�Br +

BiCI3 (5.0 mol %) »

+

R' = CH3, Ph, CI

11

BiCI3, AI

BiCI3 (0.5 eq)

BiCI3 - 1 .5 Znl2

R1 R2 F< H R3

(65-78 %)

o � R �� R1 (70-92 %)

o

R�

Scheme 1.11

OH Zn or Fe BiCI3

+ R3� R1 R2 x = CI, Br, I (45 - 99 %)

Bismuth(III) bromide has been reported as a catalyst for the oxidation of epoxides to

cyclic carbonates22 (scheme 1. 12), the deprotection of alkyl TBDMS ethers23 (scheme 1. 13), the

synthesis of nucleosides24, the formation of ethers25 (scheme 1. 14), and the synthesis of

tetrahydroquinoline derivatives26 (scheme 1. 15).

Scheme 1.12

Scheme 1.13

Scheme 1.14

o Ph�

BiBr3 ( 1 0 mol %)

OSitBuMe2 �ositBuMe, _B _iB _ r.::.-3 .:..,.(3 _ m_ o_ I _%...:..., ) )loll!>-y wetCH3CN Br OSitBuMe2 �OH Br

(81 -85 %)

BiBr3 (1 -3 mol %) )10 CH3CN, rt

12

Scheme 1.15

BiBr3 (5-20 mol %)

OH

n = 1 ,2

Bismuth(III) nitrate has also received significant attention in the literature. Bismuth(III)

nitrate has been utilized as a catalyst for the oxidation of alcohols27 (scheme 1.16), the oxidation

of sulfides to sulfoxides28 (scheme 1.17), the deprotection of acetals29 (scheme 1.18) and

thioacetals30, the synthesis of acylals from aldehydes3! (scheme 1.19), and the Biginelli

reaction. 32

Scheme 1.16

Scheme 1.17

OH A R1 R2

R(S

'R2

Bi(N03h5H2O

Montmorillonite rt

Bi(N03h5H2O

CH3COOH

13

)10

]100

0 )l R1 R2

0 II

R(S

'R2 (50-85 %)

Scheme 1.18

Scheme 1.19

0

QH

I� o I�

o

Bi(N03h5H20 (0.25 eq)

EtO

Q0Et

OSitBuMe2 OSitBuMe2 76%

Bi(N03h5H20 (3-1 0 mol %) lP ROC�OCOR

(RCOhO, CH3CN Ar H

Bismuth Trifluoromethanesulfonate [Bismuth Triflate, Bi(OTf)3]

Metal triflates have received significant attention in the literature as Lewis acid

catalysts.33 Likewise, bismuth triflate is the one of the most thoroughly investigated bismuth-

based catalysts.34 Bismuth triflate is a hygroscopic white solid that exists in a hydrated form at

room temperature (Bi(OTt)3'xH20 with 1 < x < 4). Attempts to synthesize the anhydrous salt by

heating Bi(OTt)3'4H20 result in decomposition above temperatures of 100 °C.35 The final

products of this decomposition are BiF3 and H2S04. X-ray powder diffraction35 studies on

Bi(OTt)3 show that the bismuth atom is coordinated to four water molecules and four oxygen

atoms from triflate groups. It was also determined that the tetrahydrate of bismuth triflate

condenses into dimers.

Because ofthe environmentally friendly nature of bismuth salts, bismuth triflate has

received significant attention in the literature. 10, 34 Bismuth triflate has been used as a catalyst for

Diels-Alder reactions 17, 36 (scheme 1.20), Mukaiyama aldol reactions37 (scheme 1.34), Biginelli

14

reactions38 (scheme 1.21), Friedel-Crafts acylations39 (scheme 1.22) and alkylations4o, Beckmann

rearrangements4! (scheme 1.23), Michael-type reactions42 (scheme 1.24), synthesis43 and

deprotection44 of acetals, and the Sakurai allylation of a variety of functional group including

aldehydes45 (scheme 1.25), acetals46 (scheme 1.26), epoxides47 (scheme 1.27), aziridines47

(scheme 1.28), and quinones48 (scheme 1.29). This rather vast body of literature highlights the

wide applicability and versatility of bismuth triflate as a catalyst in organic synthesis.

Scheme 1.20

Scheme 1.21

x=O, S

Scheme 1.22

Bi(OTfh (0.1-10 mol %)

R1C OCI or ( R1C Oh O

Bi(OTfh (1-10 mol %)

15

Bi( OTfh

0COR1 R�

(65-96 %)

Scheme 1.23

Scheme 1.24

Scheme 1.25

Scheme 1.26

� V-{ N-OH

Polyphosphoric acid Bi(OTfb

1 00-1200C

OMe �H

o 30 %

�OMe

o

Bi(OTfb (2.0 mol %) Q �O +

+

�SnBU3

Bi(OTfb (2.0 mol %) OH

R� (65-95 %)

Bi(OTfb (1 .0 mol %) )to

CH2CI2> rt

16

MeO

96 %

OR1

R� (66-96 %)

Scheme 1.27

0

Ar�R

Scheme 1.28

Ts I N

Ar�

Scheme 1.29

0 R1VR3

I I R2

0

(�4Sn Bi(OTfb (2.0 mol %)

)100 CH2CI2, rt

(�4sn BiOTfb (2.0 mol %)

)100 CH2CI2, rt

�SiMe3

Bi(OTfb (2.0 mol %) )100

CH2CI2, rt

R

Ar� OH

(85-92 %)

C Ar �

OH R1� R2

// '-':::

OH (75-91 %)

Bismuth triflate can be synthesized in the laboratory by a variety of literature methods.

Verma and co-workers were the first to report a synthesis of bismuth triflate from bismuth(III)

trifluoracetate and triflic acid49 (scheme 1.30).

Scheme 1.30

Bi(OCOCF3b + CF3S03H (3.6 eq)

17

rt, 8 h -----l)loo1O-- Bi(OS02CF3h

Bismuth triflate has also been synthesized by treatment of triphenylbismuth with triflic acidso

(scheme 1 .3 1 ) . This method exploits the weak bismuth-carbon bonds (Bi-C bond: 1 43 KJ/mols1;

C-C bond: 447 KJ/mol) in triphenylbismuth to generate bismuth triflate. This method is not,

however, environmentally friendly because of the formation of three equivalents of benzene, a

known carcinogen.

Scheme 1.31

+ 3 TfOH -78°C

Bi(OTf)s

A greener method for the synthesis of bismuth triflate involves reaction of bismuth oxide

and triflic acid in aqueous ethanols2 (scheme 1 .32). In this procedure, bismuth triflate is isolated

by freeze-drying the solution.

Scheme 1.32

+ 6 TfOH EtOH/H20 (75125)

,., Bi(OTfb

The efficiency of bismuth triflate as a Lewis acid catalyst is especially obvious when it is

compared to other rare-earth triflates that have received considerably more attention in the

literature. Bismuth triflate is reported to be a more effective catalyst for the chlorosulfinylation

of aromatics than other triflatesS3 (scheme 1 .33) . Bismuth triflate was sucessfully employed as a

catalyst for the chlorosulfinylation of electron-rich aromatic compounds in high yields. The use

of other metal triflates, such as scandium triflate and cerium triflate, resulted in significant

amounts of sulfide byproduct 2.

1 8

Scheme 1.33

o Meo� Catalyst

1 2

Catalyst (2.0 mol %) Yield of 1 (% t Yield of2 (%t

Bi(OTf)3 99 Trace

SC(OTf)3 14 40

Ce(OTf)4 28 38

Yb(OTf)3 Trace not detected

Sb(OTf)3 75 4

a Yield determined by 1 H NMR spectroscopy

Also, bismuth triflate is a more effective catalyst for the Mukaiyama-aldol reaction37 than

other metal triflates (scheme 1 .34). I-Trimethylsilyloxycyclohexene was successfully coupled

with benzaldehyde with a low loading (1 .0 mol %) of bismuth triflate. Ytterbium(III) triflate and

yttrium(III) triflate were ineffective as catalysts for this reaction.

Scheme 1.34

Catalyst

Bi(OTf)3

SC(OTf)3

Yb(OTf)3

Y(OTf)3

aOSiMe, I +

mol %

1 .0

5 .0

5 .0

5 .0

0

uYH

0 OH Catalyst

CYD ..

CH2CI2

Temp. T Yield (%)

-70 °C 0.5 h 95

-78 °C 1 5 h 8 1

-78 °C 1 5 h trace

-78 °C 1 5 h trace

1 9

Bismuth triflate is prone to hydrolysis in water yielding triflic acid (scheme 1 .3 5). Other

rare-earth metal triflates, such as scandium triflate and lanthanum triflate are not hydrolyzed in

water. This unique property of bismuth triflate must be considered while dealing with acid-

sensitive functional groups or proposing reaction mechanisms.

Scheme 1.35

For example, Marko and coworkers have explored the role of triflic acid in the metal

triflate catalyzed acylation of alcohols54 (scheme 1 .36) . It was discovered that the rate of

benzoylation of alcohols catalyzed by bismuth triflate was greatly inhibited when the reaction

was performed in the presence 2,6-di-t-butyl-4-methylpyridine (DTBMP), a very hindered

organic base. Moreover, the reaction was successfully catalyzed using triflic acid. These data

suggest that the acylation of alcohols is actually triflic acid catalyzed. Similar observations have

been made by our group.44

Scheme 1.36

�OH

Catalyst mol % Bi(OTf)3 5 .0

Bi(OTf)3 5 .0

TfOH 8.0

DTBMP (%)

1 5 .0

o

�O)lPh

t

7 h

1 5 h

5 h a Measured by capillary GC after calibration of the response for each component

20

Conversion (%t 1 7

8

30

Bismuth triflate can also be used as a catalyst in aqueous solutions. For example, the

synthesis of2,3-disubstituted quinoxalines catalyzed by bismuth triflate in water been reported. 55

The bismuth triflate catalyzed deprotection of acyclic and cyclic acetals in aqueous THF

has also been reported44 (scheme 1 .37). This protocol also applicable to ketals and conjugated

acetals with a low loading of bismuth triflate (0. 1 - 1 .0 mol %).

Scheme 1.37

H3CXOCH3 R1 R2

0) RJ.-O

Bi(OTfh (0.1 -1 .0 mol %)

THF/H20 (80:20)

Bi(OTfh (0.1 -1 .0 mol %)

THF/H20 (80:20)

..

..

° )l R1 R2

° R)lH

Many reagents and catalysts are destroyed when exposed to small amounts of water.

This makes the use of anhydrous solvents and reagents imperative in many cases. Catalysts and

reagents must often be handled under an inert atmosphere. In contrast, most reactions catalyzed

by bismuth triflate do not require dry solvents or inert atmosphere conditions.

The environmentally friendly nature of bismuth (III) triflate coupled with its ease of

handling and inexpensive nature have prompted us to explore its utility as a catalyst for a variety

of synthetic transformations.

C. Literature Review: Allylation of Acetals

Hosomi-Sakurai Allylation of Acyclic Acetals

Some of most important organic transformations involve the formation of carbon-carbon

bonds. These methodologies are especially important in the synthesis of pharmaceuticals and

21

natural products. Methods that have been developed for the formation of carbon-carbon bonds

include the Suzuki Cross-Coupling56, Friedel-Crafts acylation57 and alkylation58, the Michael

reaction59, Olefin Metathesis6o, and Diels-Alder cyclization.61 The nucleophilic allylation of

various carbon electrophiles is also an efficient strategy for carbon-carbon bond formation. The

Hosomi-Sakurai reaction involves the Lewis or protic acid catalyzed allylation of various

electrophiles using allyl silanes. This method is commonly regarded as a mild method for

carbon-carbon bond formation. Hosomi and Sakurai first reported the TiCl4-promoted allylation

of aldehydes and ketones to yield homoallyl alcohols62 (scheme 1.38).

Scheme 1.38

TiCI4 (0.5 eq)

They also successfully extended this methodology to the allylation of acyclic acetals63 (scheme

1.39). This represents an efficient synthesis of homo allyl ethers from readily available acetal

starting materials. Following their report, the allylation of acyclic acetals to yield homo allyl

ethers has since been well studied with a number of different Lewis acid catalysts. These include

diphenylboryl triflate68, bis(fluorosulfonyl)imide69, montmorillonite 70, CuBr7\ tris(p-

bromophenyl)aminium hexachloroantimonate72, Sc(OTf)3 73 , and BiBr3 .74 Many of the catalysts

previously employed for this synthesis are corrosive, for example AICl], TiC14, and TMSOTf, or

toxic, for example BF3"Et20. Additionally, stoichiometric catalyst loadings are often necessary.

Low temperatures and anhydrous conditions are also required in several of these reported

22

protocols. These conditions detract from the utility of these procedures in the industry because

of environmental and safety concerns.

Scheme 1.39

Our group has reported the bismuth(III) triflate-catalyzed allylation of acyclic acetals and

ketals to yield homoallyl ethers in good yields75 (scheme 1 .40). The allylation reactions

proceeded smoothly at room temperature with a low catalyst loading (1 .0 mol %).

Scheme 1.40

Bi(OTf)s (1.0 mol %) ..

This procedure provides a highly catalytic and environmentally friendly route to

homoallyl ethers compared to previously reported methodologies.

Hosomi-Sakurai Allylation of Aldehydes

In contrast to the allylation of acyclic acetals, the allylation of aldehydes and carbonyl

compounds to yield homoallyl ethers has received relatively little attention in the literature.

Sakurai and co-workers reported the allylation of aldehydes and ketones catalyzed by

iodotrimethylsilane in the presence of alkoxysilanes to yield homo allyl ethers 76 (scheme 1 .4 1 ) .

Trimethylsilyl triflate has also been used as a catalyst for the allylation of aldehydes in the

23

presence of alkoxysilanes to yield benzyl homo allyl ethers and n-hexyl homoallyl ethers.77 Two

disadvantages of this method are the utilization of a corrosive catalyst and the use of carbon

tetrachloride, a carcinogenic and environmentally harmful solvent.

Scheme 1.41

M e3Si I (10.0 mol %) �

We have recently reported the iron(III) p-toluenesulfonate catalyzed allylation of

aldehydes and acetals to yield homoallyl ethers78 (scheme 1 .42) . The direct conversion of

aldehydes to the corresponding homo allyl ether is advantageous because few acetals are

commercially available and must be typically synthesized from the corresponding aldehyde. In

addition, many acetals have a poor shelf life due to their acid-sensitive nature. Moreover, most

methods in the literature for the allylation of acetals only report the synthesis of homo allyl

methyl or ethyl ethers. These compounds are not very amenable to further synthetic

manipulation since the alkyl group appended to the homo allyl ether oxygen is an inert methyl or

ethyl group. A one-pot procedure utilizing alkoxysilanes allows for the installation of functional

groups that are more amenable to further synthetic manipulation. This is possible because a wide

range of alkoxysilanes is commercially available including benzyloxytrimethylsilane,

ethoxytrimethylsilane, and allyloxytrimethylsilane.

24

Scheme 1.42

o

R(,llH �SiMe3

Fe(OTsh6H20 CH3CN, rt

We reported the allylation of aldehydes and ketones under mild conditions to yield

homo allyl methyl ethers, homo allyl ethyl ethers, homoallyl allyl ethers, and homoallyl benzyl

ethers. This protocol was applicable to both aliphatic and aryl aldehydes with low catalyst

loadings ( 1 .0- 1 0.0 mol %). This method is especially attractive because ofthe utilization of

iron(III) tosylate, an inexpensive and non-corrosive Lewis acid catalyst.

Our group has also reported the one-pot synthesis of homo allyl ethers from aldehydes

catalyzed by bismuth(III) triflate79 (scheme 1 .43). Trialkylorthoforrnates or alkoxysilanes were

employed to generate acetals or oxenium ions respectively, which can then undergo allylation to

yield homoallyl ethers.

Scheme 1.43

HC(OR1b or R10SiMe3

�SiMe3

Bi(OTfb (0.1-5.0 mol %) CH3CN or CH2CI2 27-82 %

This methodology was applicable to a variety of aryl aldehydes with a low catalyst loading. The

use of alkoxytrimethylsilanes is particularly attractive because it allows for the installation of

synthetically useful allyl or benzyl groups at the homo allyl ether oxygen.

25

The one-pot synthesis of homo allyl acetates from aldehydes catalyzed by bismuth triflate has

also been reported (scheme 1 .44). This procedure utilized acetic anhydride to generate the

corresponding acylals, which can then undergo allylation to yield homo allyl acetates. Aldehydes

with strongly electron-donating groups (p-methoxy) underwent diallylation under the reaction

conditions. The use of a relatively non-corrosive and non-toxic catalyst coupled with the wide

availability of aldehydes makes this an attractive route to homo allyl acetates

Scheme 1.44

(CH3COhO

�SiMe3

Bi(OTf)s (1.0 mol %)

CH3CN

OAe

R� 57-66 %

Hosomi-Sakurai Allylation of 1,3-Dioxolanes and 1,3-Dioxanes

Dioxolanes and dioxanes (fig. 1 .3 ) have been primarily utilized as acid-labile protecting

groups in organic synthesis. 80

Figure 1.3

1,3-dioxolane 1,3-dioxane

However, cyclic acetals can also be converted to other useful functional groups in the course of a

synthesis. For example, the synthesis of hydroxy esters by oxidation of cyclic acetals with m-

chloroperbenzoic acid has been reported8 1 (scheme 1 .45).

26

Scheme 1.45

R2�R3

°XO

R1 H n

= 0, 1

BF3·Et20 (10 mol %) mCPBA (1 eq) ° R2 R3 --b -en- z- e-n -e,- rt----i· .... R(1l0�OH

Cyclic acetals have received very little attention in the literature as substrates in the Hosomi-

Sakurai reaction. Nevertheless, the ring-opening allylation of cyclic acetals ought to lead to the

synthesis of highly functionalized alcohols (scheme 1 .46).

Scheme 1.46

�SiMe3 . _-------------- .....

Lewis Acid

Kuwajima and co-workers reported the allylation of a substituted 1 ,3 -dioxolane catalyzed

by TiCI4, AICh, and SnC14.82 They found that the regioselectivity of ring-opening of a 4,4-

dimethyl substituted 1 ,3-dioxolane was dependent on the Lewis acid used and the order of

addition of reagents (scheme 1 .47). When TiC14 was employed as the Lewis acid,

regioselectivity was dependent on the order of addition of allyltrimethylsilane and TiC14. When

AICh and SnC14 were used, isomer 4 was the major product ( 1 :99, 3:4). They also reported that

the allylation did not proceed with TMSOTf as the catalyst and allyltrimethylsilane as the allyl

source. Instead, allyltributyltin, a highly toxic organotin reagent, was necessary to afford the

desired allylated product under these conditions.

27

Scheme 1.47

Lewis Acid

O�OH

C6H13--Z� �SiMe3 O�OH

C6H13� + C6H13� )Po

CH2CI2 3 4

Mead and co-workers have reported the allylation of spiroketals using BF3'EhO, TiC14,

and TMSOTf as Lewis acid catalysts83 (scheme 1 .48). Stoichiometric catalyst loadings and low

temperature conditions were necessary to promote the reaction. A mixture ofmonoallylated (5)

and diallylated (6) products was obtained in most cases. Because of these factors, this procedure

is not very attractive within the context of Green Chemistry.

Scheme 1.48

�SiMe3

TMSOTf, TiCI4, or BF3'OEt2

The allylation of a cyclic acetal derived from �-D-ribo-hexopyranose has been reported84

(scheme 1 .49) . The allylation required stoichiometric loadings of both TMSOTf (3 eq) and

BF3'EhO (3 eq) with allyltrimethylsilane (1 2.3 eq) as the allylating agent. Moreover, the

allylation yielded a mixture of isomers, only one of which, 7, was carried on in the synthesis.

28

Scheme 1.49

7:8=10 :1

Morelli and co-workers have reported the TiCl4 promoted allylation of 4-trifluoromethyl-

1 ,3-dioxolanes85 (scheme 1 .50). This protocol was extended to only three aliphatic dioxolanes.

Furthermore, highly toxic allyltributyltin was used as the source of the allyl group and a

stoichiometric loading of TiCl4 was necessary to afford the desired homo allyl ether product.

Scheme 1.50

CF3

J�Me R 0

TiCI4

�SnBu3

CH2CI2• OoC 1 5 m in

Me)--(CF3

o OH

.. R� 62% - 85%

The allylation of 1 ,3-dioxolanes catalyzed by Sn(OTf)2 in the presence of alkoxysilanes

has been reported86 (scheme 1 .5 1 ). This synthesis yielded homo allyl ethers as a result of

exchange between the alkoxysilane and the 1 ,3-dioxolane. The authors propose that the

allylation of the acyclic acetal resulting from the exchange is faster than the allylation of the

cyclic acetal. This reaction was applicable to a number of aliphatic and aryl dioxolanes in good

yields, but a stoichiometric catalyst loading was necessary.

29

Scheme 1.51

�SiMe3 ( 1 .4 eq) R30SiMe3 (2.0 eq)

Sn(OTfh (1.0 eq) CH3CN, -20 DC

exchange

)10 OR3

R1� 41 -97%

fast OR3

R1� observed product

The allylation of a number of 1 ,3-dioxolanes and 1 ,3-dioxanes catalyzed by TMSOTfhas

been reported by Hunter and co-workers87 (scheme 1 .52). This method utilized allyl borates as

the source of the allyl group. The allyl borate reagents are not commercially available and must

be synthesized in lab. A corrosive catalyst (TMSOTf) was employed in stoichiometric quantities

and low temperature conditions were required (-78 °C). In a few cases, an alcohol byproduct

arising from reduction of the cyclic acetal under the reaction conditions was also isolated in

significant yield.

Scheme 1.52

n = 1 , 2 TMSOTf ( 1 .2 eq)

THF, -78 DC to 0 DC

+

38-71 % reduction product

Denmark and co-workers have reported one of the few Sakurai-Hosomi protocols utilizing 1 ,3 -

dioxanes as substrates88 (scheme 1 .53). The allylation of 4,6-dimethyl-2-hexyl-l ,3-dioxane

proceeded with a high degree of diastereoselectivity (270: 1 ) with a stoichiometric loading of

TiCLJTi(O-i-Pr)4 ( 1 1 eq) and allyltributyltin (8 eq) as the allylating agent. The

30

diastereoselectivity was much lower when allyltrimethylsilane was employed (56: 1 ). The use of

a corrosive Ti-based catalyst and a toxic organotin compound in superstoichiometric amounts

detracts from the utility of this method.

Scheme 1.53

�SnBU3 (8 eq)

TiCI41Ti(O-i-Pr)4 (11 eq)

CH2CI2 -78 QC

�SiMe3 (8 eq)

TiCI41Ti(O-i-Pr)4 (11 eq) CH2CI2 -78 QC

QH3 CH3

O�OH

n-C6H13� 9

+

100% dr 9/10 = 270/1

+

100% dr 9/10 = 56/1

QH3 CH3

9�OH

n-C6H13�

The lack of a highly catalytic, widely applicable, and environmentally-friendly method

for the allylation of cyclic acetals prompted us to explore the bismuth(III) triflate-catalyzed

allylation of cyclic acetals. The development of greener methods for allylation chemistry is of

particular relevance because of increasing environmental concerns and the importance of carbon-

carbon bond forming reactions in organic synthesis. Bismuth-based Lewis acids are particularly

attractive in this respect because they are relatively non-toxic, non-corrosive, and inexpensive.

3 1

II. Results and Discussion

A. Allylation of 1 ,3-Dioxolanes followed by in situ Derivitization with Acid Anhydrides

Catalyzed by Bismuth(III) Triflate

The lack of a highly catalytic and environmentally benign method for the ring-opening

allylation of 1 ,3-dioxolanes (scheme 2 . 1 ) prompted our interest in investigating the utility of

bismuth(III) triflate as a catalyst for this transformation. In contrast to the Hosomi-Sakurai

allylation of aldehydes62, 76-79 and acyclic acetals63-7S, the allylation of cyclic acetals has received

very little attention.

Scheme 2.1

�x

Catalyst

Solvent

Bismuth triflate was not an effective catalyst for the allylation of 1 ,3-dioxolanes to yield

the expected alcohol products (scheme 2.2) . Instead, a mixture of starting material and the

corresponding aldehyde was isolated.

Scheme 2.2

Bi(OTfh

were isolated

32

It was reasoned that one way to push the reaction might be to trap the putative alkoxide

intermediate that results from addition of the allyl group with an electrophile (scheme 2.3) . This

method would represent a multi component reaction in which the alkoxide is derivatized in a one-

pot process.

Scheme 2.3

�SiM e3

Bi(OTf )3

Solvent

O�OE

R� ' R�

Attempts to capture the alkoxide with trimethylsilylchloride or p-toluenesulfonic anhydride were

unsuccessful (scheme 2.4). In both cases, a mixture of starting material and aldehyde was

obtained.

Scheme 2.4

TMSCI (1 .2 eq) O�OTMS

�SiMe3 ( 1 .2 eq) I ----------------�.� Ph�

Bi(OTf)s (2.0 mol %)

Ts20 ( 1 .7 eq)

�SiMe3 ( 1 .7 eq) 0 Bi(OTf)s (2.0 mol %) 7 ,.

CH3CN

work-up / / /7.

Gratifyingly, we were able to trap the alkoxide intermediate with acetic anhydride

(scheme 2 .5), a protocol that allowed for the synthesis of highly functionalized esters in a one-

33

pot process. There are no literature reports for the allylation of cyclic acetals involving an in situ

derivatization of the alkoxide, and thus, this new procedure is especially attractive. Such

multi component reactions reduce the time and number of steps associated with a synthesis

because isolation of intermediates is unnecessary.

Scheme 2.5

AC20 ( 1 .7x)

�SiMe3 ( 1 .7x)

B i (OTfb (2.0 mol %)

CH3C N, 0 °C

o�Oy Ph�O

An efficient one-pot procedure for the synthesis of highly functionalized ester products was thus

developed.89 The protocol was applied to the allylation of a number of aryl and aliphatic

dioxolanes (table 2 . 1 ).

Although the initial work was performed using acetonitrile as the solvent, the reactions

were also found to proceed smoothly under solvent-free conditions. This reduces the amount of

waste associated with the reaction. Products were initially isolated by aqueous work-up followed

by filtration through a silica column. The unacceptably low purity of crude products and the

difficulty of removing anhydrides during work-up prompted us to consider a direct filtration of

the reaction mixture through a silica gel column. This simple purification eliminates the need for

a tedious aqueous work-up and reduces the total amount of organic waste associated with the

synthesis.

34

Table 2.1: Bismuth(III) Triflate Catalyzed Allylation of 1,3-Dioxolanes

O�OCOR2

2.0 mol % Bi(OTfb I .. R 1

� �SiMe3 (1.7x)

(R2COhO (1. 7x) o DC

RI R2 t Yield (%)

p-CIC6H4 Me 40 min 67a

p-CH3C6H4 Me 1 h 43b

o-BrC6H4 Me 1 h 62b,c

o-FC6H4 Me 1 h 6 1 b

m-BrC6H4 Me 45 min 73b

CH3(CH2)8 Me 21 h 30 min 73b,c

p-CIC6H4 iPr 35 min 36a

O-BrC6H4 iPr 4 h 30 min 47a

o-CIC6H4 iPr Ih 1 5 min 53a

CH3(CH2)8 iPr 3 h 35 min 44a

O-BrC6H4 tBu 2 h 40 min 54a

a Reaction mixture was loaded onto silica gel and eluted with EtOAc/ heptane

b Product was isolated by aqueous work-up followed by flash chromatography

c Reaction carried out in CH3CN at rt

This transformation was successful with a low catalyst loading (2.0 mol %) and under

mild, solvent-free reaction conditions. This contrasts sharply with previous reports in which

stoichiometric loadings of corrosive catalysts (TiC14, TMSOTf, SnCI4) were necessary to

35

promote allylation. Reaction times were relatively short ( 1 -4 h), with the exception of aliphatic

dioxolanes which required longer reaction times. All reactions proceeded at 0 0 C and under

mild, solvent-free conditions. Many methods reported to date require low temperature

conditions (-78 0 C).

Moreover, many of the previous procedures were only applied to a few dioxolanes. Our protocol

was amenable to a variety of aliphatic and substituted aryl dioxolanes. Electron-rich aryl

dioxolanes underwent allylation with a low catalyst loading (2.0 mol %).

A variety of acid anhydrides such as acetic anhydride, isobutyric anhydride and

trimethylacetic anhydride were successfully employed for the in situ derivatization of the

alkoxide intermediate. However, the yield of the product dropped with use of hindered

anhydrides. Thus, structural diversity can be introduced into the ester product by altering both

the dioxolane and acid anhydride utilized. Furthermore, the highly functionalized product is

formed via a one-pot procedure from commercially available or readily accessible dioxolane

starting materials.

Attempts to apply the protocol to the allylation of 1 ,3 -dioxolanes derived from ketones

were unsuccessful. A mixture of starting material and acetophenone was isolated when the 1 ,3 -

dioxolane derived from acetophenone was subjected to the established reaction conditions

(scheme 2.6).

36

Scheme 2.6

�SiMe3 ( 1 .7 eq)

AC20 ( 1 .7 eq)

Bi(OTfh (2.0 mol %) o De

/

B. Mechanistic Studies on the Bismuth(IH) Triflate-Catalyzed Allylation of Dioxolanes

In order to determine the mechanism by which bismuth(III) triflate is catalyzing the

allylation of dioxolanes, a number of control experiments were performed (scheme 2.7). Though

it was hypothesized that bismuth triflate is acting as a Lewis acid, it is also possible that the

reaction is protic acid catalyzed. Triflic acid generated in solution by the hydrolysis of bismuth

triflate could potentially be catalyzing the allylation of dioxolanes.

As was already established, the allylation of 2-(2-bromophenyl)-1 ,3-dioxolane catalyzed

by bismuth triflate (2.0 mol %) proceeded to completion in an hour. The allylation does not

proceed in the absence of a catalyst. When triflic acid (5.0 mol %) was used as a catalyst for the

allylation, a mixture of desired product and aldehyde was detected by GC analysis of the reaction

mixture.

The bismuth triflate-catalyzed allylation was also conducted in the presence of 1 ,8-

(dimethylamino)napthalene (Proton Sponge™)90 (figure 2. 1 ).

37

Figure 2.1

(CH�H3)'

VU Proton Sponge ™

1 ,8-bis( dimethylamino )napthalene

Under these conditions, no product or aldehyde was observed by GC. While this might suggest

that the reaction is protic acid catalyzed, it is also possible that the amino functionalities of 1 ,8-

(dimethyl amino )napthalene are strongly coordinating to bismuth triflate, rendering it unable to

catalyze the reaction. More studies are necessary to determine bismuth triflate's role in

catalyzing the allylation of dioxolanes.

Scheme 2.7

o� �o Vsr

�SiMe3 ( 1 .7x)

AC20 ( 1 .7x)

2.0 mol % Bi(OTfb

No Catalyst

2.0 mol % Bi(OTfb

7 mol % proton sponge

38

o� o� II 1 h, 90% product by GC

O-BrC6H4� 0

No product

1 h, 40% product, 55% aldehyde by GC

No product

A proposed mechanism for allylation involving activation of the dioxolane by bismuth

triflate is shown (scheme 2.8).

Scheme 2.8

RJ....) + Bi(OTfh

. . � 1

° �oSiMe3

+ Bi(OTfh +

.k,.> Tf0 8 R )0'" . <±> BI(OTf)2

�SiMe3 2

+ TfOSiMe3

/'... .0- Bi(OTfh O� ......" • •

------�.� R� 3

C. Allylation of 1,3-Dioxanes followed by in situ Derivitization with Acid Anhydrides


When compared to the allylation of 1 ,3-dioxolanes, there is very little precedent for the

allylation of 1 ,3-dioxanes in the literature. Furthermore, the established methods utilize

stoichiometric quantities of corrosive catalysts (TiCI4/Ti(O-i-Pr)4 or TMSOTf). Hunter and

coworkers utilized allyl borates as the source of the allyl group87 (scheme 1 .52). These

compounds must be prepared in lab, detracting from the utility of this procedure. Denmark and

coworkers utilized a large excess (8 eq) of allyltrimethylsilane or the highly toxic

allyltributylstannane as the allyl source88 (scheme 1 .53). Thus, our goal was to apply the

previously developed allylation methodology to the allylation of 1 ,3-dioxanes. This would

constitute the first catalytic allylation of 1 ,3 -dioxanes reported in the literature.

39

The previously developed procedure was applied to the allylation of a number of aryl and

aliphatic 1 ,3-dioxanes (table 2.2). Though the acetal center is more electron-rich in dioxanes

than dioxolanes as supported by J 3C NMR data, the allylations all proceeded to completion with

a low catalyst loading (2.0 mol %). In all cases, acetic anhydride was used to derivatize the

alkoxides in situ. The resulting functionalized esters were isolated in moderate to good yields.

Table 2.2: Bismuth(III) Triflate Catalyzed Allylation of 1, 3-Dioxanes

0

R,1) 2.0 mol % Bi(OTf)s O�O)lGH3 .. R1� �SiMe3 ( 1 .7x)

(GH3GObO (1 .7x)

O DG R t Yielda (%)

O-BrC6H4 1 h 30 min 79

p-BrC6H4 2 h 65

p-CIC6H4 2 h 70

p-CH3C6H4 1 h 30 min 60

m-CH3OC6H4 1 h 30 min 70

CH3(CH2)s 4 h 75

BrCH2CH2 2 h 30 min 70

a Reaction mixture was loaded onto silica gel and eluted with EtOAcl heptane

The allylation of 5 ,5-dimethyl substituted 1 ,3-dioxanes was also explored using the

developed conditions. The allylation and in situ derivatization of aryl and aliphatic 5 ,5-

dimethyl- l ,3-dioxanes was successful under mild conditions (table 2.3). The ester products were

isolated in moderate to good yields in all cases.

40

Table 2.3: Bismuth(III) Triflate Catalyzed Allylation of 5, 5-Dimethyl -l, 3-Dioxanes

o

2.0 mol % Bi(OTfb O�O)lCH3

-------!>-I> R1� �SiMe3 (1 .7x)

R

p-CIC6H4

p-CH3C6H4

CH3(CH2)s

(CH3CObO ( 1 .7x)

O DC

t

1 0 min

30 min

3 h 30 min

Yield (%)

a Reaction mixture was loaded onto silica gel and eluted with EtOAcI heptane. b Product was

isolated by aqueous work-up followed by flash chromatography.

D. AUylation of 1,3-Dithianes followed by in situ Derivitization with Acid Anhydrides


1 ,3-Dithianes have received significant attention in the literature as protecting groups for

carbonyl compounds.80 Also, their application in the "Umpolung" chemistry pioneered by

Seebach and Corey is well precedented91 (scheme 2.9).

Scheme 2.9

n-BuLi

THF, - 30 DC

41

Dithianes can be also be potentially converted to other useful functional groups. To date,

there has been no report of a Hosomi-Sakurai type allylation of dithianes to yield functionalized

thiols (scheme 2. 1 0) .

Scheme 2.10

Lewis Acid Solvent

S�SH

R�

This total lack of literature precedent for the allylation of 1 ,3-dithianes prompted our interest in

extending the established bismuth(III) triflate catalyzed allylation methodology to this

functionality. A one-pot allylation and in situ derivatization of 1 ,3-dithianes with acid

anhydrides would constitute an efficient synthesis of functionalized thioesters (scheme 2. 1 1 ) .

Scheme 2.11

�SiMe3 ( 1 .7 eq)

(CH3COhO ( 1 .7 eq)

Bi(OTfh (2.0 mol %)

O OC

Initial attempts to allylate 2-( 4-chlorophenyl)-1 ,3-dithiane to yield the corresponding

functionalized thiol were unsuccessful (scheme 2. 12). GC analysis of the reaction mixture

indicated that no reaction was taking place.

42

Scheme 2.12

�SiMe3 ( 1 .7 eq)

Bi(OTfh ( 1 0 mol %)

CH3CN, O OC

7

However, by using a protocol similar to the allylation of dioxolanes and dioxanes, the

thiolate intermediate was successfully trapped with acetic anhydride to yield the corresponding

thioester. This strategy was applied to a handful of aryl and aliphatic dithianes, yielding the

corresponding thioesters in moderate to good yields (table 2.4).

Table 2.4: Bismuth(III) Triflate Catalyzed Allylation of 1,3-Dithianes

�SiMe3 ( 1 .7 eq) 0

RJ) (CH3CO)20 ( 1 .7 eq) S�SJl.CH3 ..

R� Bi(OTfh

O OC

R mol % Bi(OTf)3 t Yieldb (%)

C6HS 2.0a 3 h 45 min 78

p-CIC6H4 2.0 2 h 45 min 65

m-CH3C6H4 4.0 4 h 30 min 74

CH3(CH2)8 1 0.0 3 h 30 min 63

a An additional 2.0 mol % Bi(OTf)3 was added after 3 h. b Reaction mixture was loaded onto

silica gel and eluted with EtOAc/ heptane.

The allylation of 1 ,3-dithianes proceeded smoothly under mild, solvent-free conditions with low

catalyst loadings (2.0 -1 0.0 mol %). Although allylation of dioxolanes and dioxanes proceeded

43

with a 2.0 mol % loading of bismuth (III) trifiate, electron-rich aryl dithianes and aliphatic

dithianes required more catalyst (4.0 - 1 0.0 mol %) for the reactions to proceed to completion.

To the best of our knowledge, this procedure represents the first example ofthe

application of 1 ,3-dithianes as substrates for the Hosomi-Sakurai reaction. Furthermore, the

method utilizes a non-toxic and non-corrosive catalyst and solvent-free conditions.

Conclusions

A robust and highly catalytic method for the allylation and in situ derivatization of a

number of cyclic acetals (dioxolanes, dioxanes, and dithianes) has been developed. There has

been little precedent in the literature for the allylation of these functionalities. Most reagents

used to date for the allylation of cyclic acetals are highly corrosive or toxic and are often

required in stoichiometric amounts. In contrast, the use of a relatively non-toxic and non

corrosive bismuth(III) based catalyst and the lack of an aqueous waste stream make the

developed methodology environmentally benign and attractive.

44

III. Experimental

A. General Experimental:

Bismuth(III) triflate was purchased from Aldrich Chemical Company and stored under vacuum.

Allyltrimethylsilane was purchased from Acros Chemical Company or Aldrich Chemical

Company. Acetic anhydride was purchased from Fisher Scientific. Dioxanes and dithianes were

prepared in lab following procedures developed in our group or literature protocols.80 Products

were analyzed using a lEOL Eclipse NMR Spectrometer at 270 MHz for lH NMR and 67.5

MHz for I 3C NMR in CDCb as the solvent. GC analysis was performed on a Varian CP-3800

Gas Chromatograph equipped with a 30 m silica-packed column with a diameter of 0.25 mm

(Conditions: hold at 1 00 °C for 1 min; ramp at 30 °C/min until 220 °c ; hold at 220 °C; flow rate;

2 .0 mL/min of He). Thin-layer Chromatography was performed on alumina backed silica gel

plates. Spots were visualized under UV light (when a UV active chromophore was present) and

by spraying the plate with phosphomolybdic acid followed by heating. Purifications were

performed by flash chromatography on silica gel.92 Products were characterized by lH NMR,

I 3C NMR, and GC. Satisfactory elemental analysis or High Resolution Mass Spectrometry

(HRMS) data was obtained for all new compounds.

45

B. Bismuth(III) Triflate Catalyzed Allylation of 1,3-Dioxanes

Allylation of 2-(2-bromophenyl)-1,3-dioxane (MJS2057fr2051)

�SiMe3 (1 .7 eq)

AC20 ( 1 .7 eq)

2.0 mol % Bi(OTf)s D oC

o O�O� � UO� Br

A homogeneous mixture of 2-(2-bromophenyl)-1 ,3-dioxane (0.2450 g, 1 .008 mmol),

allyltrimethylsilane (0.2723 mL, 0. 1958 g, 1 .7 1 3 mmol, 1 .7 eq), and acetic anhydride (0. 1 620

mL, 0. 1 749 g, 1 .7 1 3 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf

as bismuth(III) triflate (0.0132 g, 0.0202 mmol, 2.0 mol %) was added. The reaction mixture

immediately acquired a light yellow color. Reaction progress was followed by gas

chromatography. After 1 h 30 min, the reaction mixture was loaded onto 65 g of silica gel and

eluted with EtOAc/heptane (5/95, v/v). Fifty-eight fractions (8 mL) were collected after a 1 00

mL prefraction. Fractions 20 to 5 1 were combined and concentrated to yield 0.26 g (79 %) of a

clear, colorless liquid product that was determined to be 97 % pure by GC analysis and IH & l 3C

NMR spectroscopy. IH NMR: () 1 .84- 1 .89 (m, 2 H), 1 .99 (s, 3 H), 2.39-2.44 (m, 2 H), 3 .34-3 .38

(m, 2 H), 4. 1 3-4. 1 8 (t, 2 H, J= 6.43 Hz), 4.68-4.71 (m, 1 H), 5 .00-5 .07 (m, 2 H), 5 .80-5 .86 (m, 1

H). 7. 1 0-7.5 1 (m, 4 H). l 3C: ( 1 5 peaks) () 1 7 1 .0, 141 .2, 1 34.4 1 32.6, 128.7, 1 27.6, 1 27.6, 1 22.9,

1 1 7.0, 80.2, 65 .4, 6 1 .6, 4 1 . 1 , 28.9, 20.9. HRMS-EI (mlz) : M+ calcd for Cl sHI9Br03Na,

349.04 1 5 ; found, 349.0423 .

46

Allylation of 2-( 4-bromophenyl)-1,3-dioxane (MJSl 185fr5069)

�SiMe3 ( 1 .7 eq)

AC20 ( 1 .7 eq)

2.0 mol % Bi(OTf)s D oC

A homogenous mixture of 2-(4-bromophenyl)- 1 ,3-dioxane (0.2501 g, 1 .029 mmol),

allyltrimethylsilane (0.2779 mL, 0. 1 998 g, 1 .749 mmol, 1 .7 eq), and acetic anhydride (0. 1 653

mL, 0 . 1 785 g, 1 .749 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf

as bismuth(III) triflate (0.01 3 5 g, 0.0206 mmol, 2.0 mol %) was added. The reaction mixture


chromatography. After 2 h, the reaction mixture was loaded onto 65 g of silica gel and eluted

with EtOAc/ heptane (5/95, v/v). Seventy-two fractions (8 mL) were collected after a 1 00 mL

prefraction. Fractions 50 to 69 were combined and concentrated to yield 0.22 g (65 %) of a

clear, colorless liquid product that was determined to be 98 % pure by GC analysis and IH & 1 3C

NMR spectroscopy. IH NMR: () 1 .82- 1 .86 (m, 2 H), 1 .98 (s, 3 H), 2.32-2.50 (m, 2 H), 3 .3 1 -3 .34

(m, 2 H), 4. 1 0-4. 1 5 (m, 3 H), 4.96-5.02 (m, 1 H), 5.65-5.76 (m, 1 H), 7. 1 1 -7. 1 4 (d, 2 H, J = 8. 1 5

Hz), 7.42-7.45 (d, 2 H, J = 8 . 1 5 Hz). 13C: ( 1 3 peaks) () 1 7 1 .0, 141 . 1 , 1 34.2, 1 3 1 .4, 1 28 .3 , 1 2 1 .3 ,

1 1 7 .2, 8 1 .5 , 65.0, 6 1 .6, 42.4, 28.9, 20.9. HRMS-EI (mlz): M+ calcd for CI SHI 9Br03Na,

349.04 1 5 ; found, 349.04 17.

47

AHylation of 2-( 4-chlorophenyl)-1,3-dioxane (MJS 1179fr8099)

�SiMe3 ( 1 .7 eq)

AC20 (1 .7 eq)

2.0 mol % Bi(OTf)s O OC

A homogenous mixture of 2-(4-chlorophenyl)- 1 ,3-dioxane (0.2500 g, 1 .259 mmol) ,

allyltrimethylsilane (0.3399 mL, 0.2445 g, 2. 140 mmol, 1 .7 eq), and acetic anhydride (0.2022

mL, 0 .2 1 84 g, 2 . 140 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf

as bismuth(III) triflate (0.01 65 g, 0.0252 mmol, 2.0 mol %) was added. The reaction mixture


chromatography. After 2 h, the reaction mixture was loaded onto 66 g of silica gel and eluted

with EtOAc/heptane (5/95, v/v). One hundred and six fractions (4 mL) were collected.

Fractions 80 to 99 were combined and concentrated to yield 0.25 g (70 %) of a clear, colorless

liquid product that was determined to be 98 % pure by GC analysis and IH & 1 3C spectroscopy.

IH NMR : 0 1 . 82- 1 .89 (m, 2 H), 1 .98 (s, 3 H), 2.32-2.54 (m, 2 H), 3 .3 1 -3 .34 (m, 2 H), 4. 1 1 -4.20

(m, 3 H), 4.97-5 .03 (m, 2 H), 5 .66-5 .76 (m, 1 H), 7 . 1 7-7.3 1 (m, 4 H). 13C: ( 1 3 peaks) 0 1 7 1 .0,

1 40.6, 1 34.2, 1 3 3 . 1 , 1 28.4, 128.0, 1 1 7.2, 8 1 .4, 65.0, 61 .5, 42.4, 28.9, 20.9. HRMS-EI (mlz) : M+

calcd for ClsHI9CI03Na, 305 .0920; found, 305.09 13 .

48

Allylation of 2-( 4-tolyl)-1,3-dioxane (MJS2051fr3052)

o �SiMe3 (1 .7 eq) O�O�

AC20 ( 1 .7 eq)

~ ----...... I � � 2.0 mol % Bi (OTf)s

H3C h-O OC

A homogenous mixture of 2-(4-tolyl)- 1 ,3-dioxane (0.2497 g, 1 .402 mmol), allyltrimethylsilane

(0.3788 mL, 0.2723 g, 2.383 mmol, 1 . 7 eq), and acetic anhydride (0.2253 mL, 0.2433 g, 2 .383

mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf as bismuth(III) triflate

(0.0 1 84 g, 0.0280 mmol, 2.0 mol %) was added. The reaction mixture immediately acquired a

bright pink color. Reaction progress was followed by gas chromatography. After 1 h 30 min,

the reaction mixture was loaded onto 60 g of silica gel and eluted with EtOAc/heptane (5/95,

v/v). Sixty fractions (8 mL) were collected. Fractions 30 to 52 were combined and concentrated

to yield 0.22 g (60 %) of a clear, colorless liquid product that was determined to be 99 % pure by

GC analysis and IH & l 3C spectroscopy. IH NMR: 0 1 .82- 1 .89 (m, 2 H), 1 .98 (s, 3 H), 2.33 (s, 3

H), 2.37-2.56 (m, 2 H), 3 .29-3 .35 (m, 2 H), 4. 1 1 -4. 1 6 (m, 3 H), 4.97-5 .05 (m, 2 H), 5 .70-5 .76 (m,

1 H). 7. 1 1 -7. 1 7 (m, 4 H). l3C: ( 14 peaks) 0 1 7 1 . 1 , 1 39.0, 1 37.2, 1 35 .0, 129.0, 1 26.6, 1 1 6.7, 82.0,

64.8 , 6 1 .8, 42,6, 29.0, 2 1 . 1 , 20.9. Anal. Calcd for C16H2203 : C, 73 .25; H, 8.45. Found: C, 73 .08;

H, 8.45.

49

Allylation of 2-(3-methoxyphenyl)-1,3-dioxane (MJS119lfr2433)

�SiMe3 ( 1 .7 eq)

AC20 ( 1 .7 eq)

2.0 mol % Bi(OTf)s O DC

o O�O�

r OCH3

A homogenous mixture of 2-(3-methoxyphenyl)-1 ,3-dioxane (0.2504 g, 1 .289 mmol),

allyltrimethylsilane (0.3483 mL, 0.2504 g, 2 . 1 92 mmol, 1 .7 eq), and acetic anhydride (0.2072

mL, 0.2237 g, 2 . 1 92 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried rbf as

bismuth(III) triflate (0.01 69 g, 0.0258 mmol, 2.0 mol %) was added. The reaction mixture

immediately acquired a dark red color. Reaction progress was followed by gas chromatography

and TLC. After 1 h 30 min, the reaction mixture was loaded onto 60 g of silica gel and eluted

with EtOAc/hexanes ( 1 0190, v/v) for fractions 1 -24 and EtOAc/hexanes (20/80, v/v) for fractions

24-57. Fifty-seven fractions (8 mL) were collected after a 1 00 mL prefraction. Fractions 24 to

3 3 were combined and concentrated to yield 0.25 g (70 %) of a clear, colorless liquid that was

determined to be 99 % pure by GC analysis and IH & J3C NMR spectroscopy. IH NMR: 0 1 .83-

1 .87 (m, 2 H), 1 .98 (s, 3 H), 2.35-2.52 (m, 2 H), 3.30-3 .38 (m, 2 H), 3 .79 (s, 3 H), 4. 1 1 -4. 1 6 (m,

3 H), 4.97-5 .05 (m, 2 H), 5 .70-5 .80 (m, 1 H), 6.78-6.85 (m, 3 H), 7.20-7.26 (m, 1 H). l 3C: ( 16

peaks) 0 1 7 1 . 1 , 1 59.7, 143 . 8, 1 34.8, 129.3, 1 1 9.0, 1 1 6.8, 1 1 2.9, 1 1 1 .9, 82.0, 65.0, 6 1 .7, 55 . 1 ,

42.5 , 28.9, 20.9. Anal. Calcd for C16H2204: C, 69.04; H, 7.97. Found: C, 68.83 ; H, 7.94.

50

Allylation of 2-nonyl-l,3-dioxane (MJS2059fr3463)

�SiMe3 ( 1 .7 eq)

2.0 mol % Bi(OTfh O OC

o O�O�

A homogenous mixture of 2-nonyl- l ,3-dioxane (0.2509 g, 1 . 1 76 mmol), allyltrimethylsilane

(0. 3 1 77 mL, 0.2284 g, 1 .999 mmol, 1 .7 eq), and acetic anhydride (0.204 1 mL, 0 . 1 889 g, 1 .999

mmol, 1 . 7 eq) was stirred at 0 °C under N2 in a flame-dried rbf as bismuth(III) triflate (0. 0 1 54 g,

0.0235 mmol, 2.0 mol %) was added. The reaction mixture immediately acquired a light yellow

color. Reaction progress was followed by gas chromatography and TLC. After 4 h, the reaction

mixture was loaded onto 75 g of silica gel and eluted with EtOAclhexanes (3/97, v/v). Sixty-six

fractions (8 mL) were collected after a 1 00 mL prefraction. Fractions 34 to 63 were combined

and concentrated to yield 0.25 g (75 %) of a clear, colorless liquid that was determined to be 97

% pure by GC analysis and IH & 1 3C NMR spectroscopy. IH NMR: b 0.85 (t, 3 H, J = 6.91 Hz),

1 .24 (s, 1 4 H), 1 .3 9- 1 .43 (m, 2 H), 1 .80- 1 .89 (m, 2 H), 2.02 (s, 3 H), 2.22 (t, 2 H, J = 6. 1 8 Hz),

3 .20-3 .29 (m, 1 H), 3 .40-3 .57 (m, 2 H), 4. 1 4 (t, 2 H, J= 6.42 Hz), 5 .00-5.06 (m, 2 H), 5 . 7 1-5 .86

(m, 1 H). 1 3C: ( 1 8 peaks) b 1 71 . 1 , 1 3 5. 1 , 1 1 6.7, 79.3, 65.2, 6 1 .8, 3 8.3 , 33 .8, 3 1 .9, 29.7, 29.6,

29.6, 29.4, 29.3 , 25 .4, 22.7, 2 1 .0, 14. 1 . HRMS-EI (mlz): M+ ca1cd for C1 sH3403Na, 321 .2406;

found, 321 .24 16.

5 1

Allylation of 2-(2-bromoethyl)-1,3-dioxane (MJS2107fr4460)

o O�O�

Br�) �SiMe3 ( 1 .7 eq)

AC20 ( 1 .7 eq) ,..

Br� 2.0 mol % Bi(OTf)s D oC

A homogenous mixture of 2-(2-bromoethyl)- 1 ,3-dioxane (0.2545 g, 1 .305 mmol),

allyltrimethylsilane (0.3525 mL, 0.2534 g, 2.2 1 8 mmol, 1 .7 eq), and acetic anhydride (0.2097

mL, 0.2264 g, 2.2 1 8 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried rbf as

bismuth(III) triflate (0.01 7 1 g, 0.0261 mmol, 2.0 mol %) was added. The reaction mixture

immediately acquired a light brown color. Reaction progress was followed by gas


eluted with EtOAc/hexanes (5/95, v/v). Sixty fractions (8 mL) were collected. Fractions 44 to

60 were combined and concentrated to yield 0.2569 g (70 %) of a clear, colorless liquid that was

determined to be 98 % pure by GC analysis and IH & I 3C NMR spectroscopy. IH NMR: b 1 . 83-

1 .96 (m, 4 H), 2.03 (s, 3 H), 2.24-2.29 (m, 2 H), 3 .45-3 . 5 1 (m, 4 H), 3 .60-3.66 (m, 1 H), 4. 1 1 -

4. 1 6 (m, 2 H), 5 .04-5. 1 0 (m, 2 H), 5 .7 1 -5 .8 1 (m, 1 H). 1 3C: ( 1 1 peaks) b 1 7 1 . 1 , 1 33 .9, 1 1 7 .6,

76.5, 65 .6, 6 1 .6, 3 7.9, 37.3, 30.4, 29.2, 2 1 .0. HRMS-EI (mlz): [M + Ht calcd for Cl IH20Br03,

279.0596; found, 279.0598.

52

C. Bismuth(III) Tritlate Catalyzed Allylation of 5,5-Dimethyl-l ,3-Dioxanes

AHylation of 2-( 4-chlorophenyl)-5,5-dimethyl-l,3-dioxane (EBl 123fr3343)

�SiMe3 ( 1 .7 eq)

AC20 ( 1 .7 eq)

2.0 mol % Bi(OTfh O OC

A homogenous mixture of 2-( 4-chlorophenyl)-5,5-dimethyl- l ,3-dioxane (0.2500 g, 1 . 1 03 mmol),

allyltrimethylsilane (0.2979 mL, 0.2 142 g, 1 .875 mmol, 1 .7 eq), and acetic anhydride (0. 1 786

mL, 0. 1 929 g, 1 . 875 mmol, 1 .7 eq) was stirred at 0 °c under N2 in a flame-dried three-neck rbf

as bismuth(III) triflate (0.0724 g, 0. 1 1 0 mmol, 1 0.0 mol %) was added. The reaction mixture

immediately acquired a bright orange color. Reaction progress was followed by gas

chromatography. After 1 0 min, the reaction mixture was stirred with 1 0% Na2C03 ( 1 5 mL) for

25 minutes. The mixture was extracted with EtOAc (3 x 1 0 m:). The combined organic layers

were washed with sat. NaCl (20 mL), dried (Na2S04), and concentrated to yield 0.3360 g (98 %)

of a yellow liquid that was determined to be 90 % pure by GC and IH NMR. The crude product

was loaded onto 22 g of silica gel and eluted with EtOAc/ heptane (2.5/97.5, v/v). Sixty-five

fractions (4 mL) were collected. Fractions 35 to 5 1 were combined and concentrated to yield

0.2534 g (74 %) of a clear, colorless liquid product that was determined to be 95 % pure by GC

analysis and IH spectroscopy. IH NMR: b 0.87 (s, 3H), 0.89 (s, 3 H), 1 .98 (s, 3 H), 2.24-2.53 (m,

2 H), 2.95-3 .05 (q, 2 H, J= 8.64 Hz), 3 .87 (dd, 2 H, J = 1 0.63, 2.2 1 Hz), 4. 1 1 -4. 16 (m, 1 H),

4.96-5 .02 (m, 2 H), 5.66-5 .81 (m, 1 H), 7. 1 5-7. 1 8 (m, 2 H), 7.26-7.30 (m, 2 H). BC: ( 14 peaks) :

b 1 71 .2, 1 40.9, 1 34.5, 1 33 .0, 1 28 .4, 1 27.9, 1 1 7.0, 8 1 .7, 74.4, 69.7, 42.6, 35 .3 , 2 1 .9, 20.9. HRMS-

EI (mlz) : � calcd for C1 7H23CI03Na, 333 . 1 233 ; found, 333 . 1 247.

53

Allylation of 2-( 4-tolyl)-5,5-dimethyl-l,3-dioxane (MJS2063frl034)

�SiMe3 ( 1 .7 eq)

2.0 mol % Bi(OTf)s o De

A homogenous mixture of 2-( 4-tolyl)-5,5-dimethyl- 1 ,3-dioxane (0.2590 g, 1 .256 mmol),

allyltrimethylsilane (0.3392 mL, 0.2439 g, 2. 1 35 mmol, 1 .7 eq), and acetic anhydride (0.20 1 8

mL, 0.21 79 g, 2 . 1 3 5 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf

as bismuth(III) triflate (0.0 165 g, 0.025 1 mmol, 2.0 mol %) was added. The reaction mixture


chromatography. After 30 min, the reaction mixture was loaded onto 60 g of silica gel and

eluted with EtOAc/heptane (5/95, v/v). Sixty fractions (8 mL) were collected after a 50 mL

prefraction. Fractions 1 0 to 34 were combined and concentrated to yield 0.30 g (83 %) of a

clear, colorless liquid product that was determined to be 99 % pure by GC analysis and IH & 1 3C

NMR spectroscopy. IH NMR: D 0.88 (s, 3 H), 0.90 (s, 3 H), 1 .99 (s, 3 H), 2.26-2.56 (m, 2 H),

2 .33 (s, 3 H), 2.94-3 .09 (dd, 2 H, J = 1 7.08, 8.64 Hz), 3 .85-3 .94 (t, 2 H, 1 0.58 Hz), 4. 1 1 -4. l 3 (m,

1 H), 4.96-5 .00 (m, 2 H). 5 .73-5 . 84 (m, 1 H), 7. l 3 (s, 4 H). 1 3C: ( 1 5 peaks) : D 1 7 1 .0, l 39.3,

l 36.9, l 35 . 1 , 1 28.8, 126.4, 1 1 6.4, 82. 1 , 74. 1 , 69.7, 42.8, 35 .3 , 2 1 .9, 2 1 .0, 20.8. Anal. Calcd for

Cl sH2603 : C, 74.45 ; H, 9.02. Found: C, 74. 1 5; H, 9.08.

54

Allylation of 2-nonyl-5,5-dimethyl-l ,3-dioxane (EB1125fr916)

�SiMe3 (1.7 eq) O� AC20 (1.7 eq) �O) -2-.0-m-O-l o-Vo-B-i(O

-T-f)-3-JSo"-

O OC

A homogenous mixture of 2-nonyl-5,5-dimethyl- l ,3-dioxane (0.2500 g, 1 .03 1 mmol),

allyltrimethylsilane (0.2786 mL, 0.2003 g, 1 .754 mmol, 1 .7 eq), and acetic anhydride (0. 1 676

mL, 0 . 1 793 g, 1 .754 mmol, 1 .7 eq) was stirred at 0 °c under N2 in a flame-dried three-neck rbf

as bismuth(III) triflate (0.0 1 35 g, 0.0206 mmol, 2.0 mol %) was added. The reaction mixture

immediately acquired a pale yellow color. Reaction progress was followed by gas

chromatography. After 3 h 30 min, the reaction mixture was stirred with 1 0% Na2C03 ( 1 5 mL)

for 25 minutes. The mixture was extracted with EtOAc (3 x 1 0 mL) . The combined organic

layers were washed with sat. NaCl (25 mL), dried (Na2S04), and concentrated to yield 0.3 1 52 g

(98 %) of a dark brown liquid that was determined to be 83 % pure by GC and 1 H NMR. The

crude product was loaded onto 12.5 g of silica gel and eluted with EtOAc/heptane (4/96, v/v).

Twenty-five fractions (4 mL) were collected after a 1 00 mL prefraction. Fractions 5 to 1 6 were

combined and concentrated to yield 0.23 1 5 g (72 %) of a clear, colorless liquid product that was

determined to be 97 % pure by GC analysis and IH & BC NMR spectroscopy. IH NMR: C 0.85-

0.89 (m, 9 H), 1 .24- 1 .41 (m, 1 6 H), 2.03 (s, 3 H), 2. 1 9 (t, 2 H, J = 6.91 Hz), 3 . 08-3.22 (m, 3 H),

3 .86 (s, 2 H), 4.97-5 .01 (m, 2 H), 5 .72-5 .83 (m, 1 H). l 3C ( 19 peaks) : C 1 7 1 .0, 1 3 5 .30, 1 1 6.48,

79.34, 74.53, 69.91 , 3 8.29, 35 .52, 33 .80, 3 1 .96, 29.8 1 , 29.69, 29.65, 29.39, 25.36, 22.73, 22.05,

20.9 1 , 14. 1 5 . HRMS-EI (mlz) : � calcd for C2oH3803Na, 349.271 9; found, 349.2735 .

55

D. Bismuth(III) Triflate Catalyzed Allylation of 1,3-Dithianes

Allylation of 2-phenyl-l,3-dithiane (MJS2071frl 135)

�SiMe3 ( 1 .7 eq)

AC20 ( 1 .7 eq)

4.0 mol % Bi(OTf)s o oe

o s�s� r

A homogenous mixture of 2-phenyl- l ,3-dithiane (0.2530 g, 1 .289 mmol), allyltrimethylsilane

(0.348 1 mL, 0.2503 g, 2 . 19 1 mmol, 1 .7 eq), and acetic anhydride (0.207 1 mL, 0.2236 g, 2. 1 9 1


(0. 0 169 g, 0.0258 mmol, 2.0 mol %) was added. The reaction mixture immediately acquired a

light yellow color. Reaction progress was followed by gas chromatography. After 3 h,

additional bismuth(III) triflate (0.0169 g, 0.0258 mmol, 2.0 mol %) was added to the reaction

mixture because starting material was detected by Gc. After 3 h 45 min, the reaction mixture

was loaded onto 70 g of silica gel and eluted with EtOAc/heptane (3/97, v/v) for the prefraction

and EtOAC/heptane (5/95, v/v) for the fractions. Forty-eight fractions (8 mL) were collected

after a 75 mL prefraction. Fractions 1 1 to 35 were combined and conc�ntrated to yield 0.28 g

(78 %) of a clear, colorless liquid product that was determined to be 98 % pure by GC analysis

and IH spectroscopy. IH NMR: b 1 .67- 1 .73 (m, 2 H), 2.27-2.37 (m, 5 H), 2.56-2.61 (t, 2 H, J =

7.43 Hz), 2.80-2.88 (m, 2 H), 3 .78-3. 84 (t, 1 H, J = 7.43 Hz), 4.95-5.05 (m, 2 H), 5 .64-5 .74 (m, 1

H), 7.24-7.30 (m, 5 H). 1 3C: ( 1 3 peaks) b 1 95 .5 , 141 .9, 1 3 5 .2, 128.4, 127 .8, 1 27. 1 , 1 1 6.9, 49.4,

40.8 , 30.5, 29.7, 29.0, 28.0. HRMS-EI (mlz) : M+ calcd for C1sH200S2, 280.0956; found,

280.0952.

56

Synthesis of 2-( 4-chlorophenyl)-1,3-dithiane (MJS2095fr1444)

o �H

CIN r'I SH SH ( 1 .2 x)

CH3S03H (1 0 .0 mol %)

CH2CI2. O DC

A solution ofp-chlorobenzaldehyde (0.5428 g, 3 .86 1 mmol) and 1 ,3-propanedithiol (0.466 1 mL,

0 .50 15 g, 4.634 mmol, 1 .2 eq) in CH2Ch ( 10 mL) was stirred at O °C in a three-neck rbf as

methane sulfonic acid (0.0250 mL, 0.37 1 g, 0.386 mmol, 1 0.0 mol %) was added. Reaction

progress was followed by gas chromatography. After 1 7 h 30 min, additional 1 ,3 -propanedithiol

(0. 1 942 mL, 0.2089 g, 1 .930 mmol, 0.5 eq) and methane sulfonic acid (0.0 125 mL, 0.01 85 g,

0 . 1 93 mmol, 5 .0 mol %) were added to the reaction mixture because SM was detected by GC.

After 22 h, the reaction mixture was stirred with 2 M NaOH (20 mL) for 1 5 min. The mixture

was extracted with CH2Ch (2 X 20 mL). The combined organic layers were washed with H20 (2

X 40 mL) and sat. NaCl (40 mL), dried (Na2S04), and concentrated to yield 0 .86 1 6 g (97 %) of a

white solid that was determined to be 95 % pure by GC analysis and IH NMR. The crude

product was loaded onto 50 g of silica gel and eluted with EtOAc/heptane (5/95, v/v). Sixty

fractions (8 mL) were collected. Fractions 14 to 44 were combined and concentrated to yield

0.74 g (83 %) of a white solid that was determined to be >99 % pure by GC and IH NMR. IH

NMR: 6 1 .82- 1 .98 (m, 1 H), 2. 1 3 -2.2 1 (m, 1 H), 2.85-3 . 1 0 (m, 4 H), 5 . 1 2 (s, 1 H), 7.25-7.38 (m,

4 H).

57

Allylation of 2-( 4-chlorophenyl)-1,3-dithiane (MJS21 19fr2346)

�SiMe3 (1 .7 eq)

2.0 mol % Bi(OTf)s o oe

A homogenous mixture of 2-(4-chlorophenyl)- 1 ,3-dithiane (02590 g, 1 . 1 22 mmol),

allyltrimethylsilane (0.3032 mL, 0.21 80 g, 1 .908 mmol, 1 .7 eq), and acetic anhydride (0. 1 803

mL, 0. 1 948 g, 1 .908 mmol, 1 .7 eq) was stirred at 0 °C under N2 in a flame-dried three-neck rbf

as bismuth(III) triflate (0.0147 g, 0.0225 mmol, 2.0 mol %) was added. The reaction mixture



eluted with EtOAc/heptane (3/97, v/v). Forty-eight fractions (8 mL) were collected after a 1 00

mL prefraction. Fractions 1 3 to 34 were combined and concentrated to yield 0.23 g (65 %) of a

clear, colorless liquid product that was determined to be 98 % pure by GC analysis and IH

spectroscopy. IH NMR: () 1 .68-1 .73 (m, 2 H), 2.26-2.3 1 (m, 5 H), 2.5 1 -2.58 (m 2 H), 2.75-2.91

(m, 2 H), 3 .75-3 . 8 1 (t, 3 H, J= 7.40 Hz), 4.96-5 .03 (m, 2 H), 5 .60-5.70 (m, 1 H), 7.24-7.26 (m, 4

H). l 3C: ( 1 3 peaks) () 1 95.6, 140.5, 1 34.8, 1 32.7, 129.2, 1 28.6, 1 1 7.3 , 48.8, 40.8 , 30.6, 29.7, 29.0,

28.0. HRMS-EI (mlz): M+ calcd for Cl sH19ClOS2, 3 1 4.0566; found, 3 14.0564.

58

Synthesis of 2-(3-tolyl)-1,3-dithiane (MJS2101crude)

(l SH SH ( 1 .7 x)

CH3S03H ( 1 0.0 mol %)

CH2CI2• O DC

A solution of m-tolualdehyde (0.508 1 g, 4.229 mmol) and 1 ,3-propanedithiol (0.723 1 mL,

0 .778 1 g, 7. 1 89 mmol, 1 .7 eq) in CH2Ch ( 10 mL) was stirred at O °C in a three-neck rbf as

methane sulfonic acid (0.0274 mL, 0.0406 g, 0.423 mmol, 1 0.0 mol %) was added. The reaction

mixture immediately acquired a cloudy white color. Reaction progress was followed by gas

chromatography. After 1 8 h, the reaction mixture was stirred with 2 M NaOH (40 mL) for 1 5

min. The mixture was extracted with CH2Ch (3 X 20 mL). The combined organic layers were

washed with H20 (2 X 40 mL) and sat. NaCI (40 mL), dried (Na2S04), and concentrated to yield

0.76 g (85 %) of a yellow liquid that was determined to be 98 % pure by GC analysis and IH

NMR. IH NMR: 0 1 .84-2.00 (m, 1 H), 2. 1 2-2. 1 9 (m, 1 H), 2 .33 (s, 3 H), 2.85-3 . 1 1 (m, 4 H), 5 . 1 2

(s, 1 H), 7 .08-7.28 (m, 4 H).

Allylation of 2-(3-tolyl)-1,3-dithiane (MJS2097fr1334)

CH3

�SiMe3 (1 .7 eq)

AC20 ( 1 .7 eq)

4.0 mol % Bi(OTfb O DC

o S�S�

~ CH3

A homogenous mixture of 2-(3-tolyl)- 1 ,3-dithiane (0.248 1 g, 1 . 1 79 mmol), allyltrimethylsilane

(0.3 1 86 mL, 0.2291 g, 2.005 mmol, 1 .7 eq), and acetic anhydride (0. 1 895 mL, 0.2047 g, 2.005

59


(0.03 1 0 g, 0.0472 mmol, 4.0 mol %) was added. Reaction progress was followed by gas

chromatography. After 3 h, the reaction mixture was stirred with 1 0% Na2C03 (20 mL) 1 5

minutes. The mixture was extracted with EtOAc (3 x 20 mL). The combined organic layers

were washed with sat. NaCl (40 mL), dried (Na2S04), and concentrated to yield 0.3263 g (94 %)

of a dark brown liquid that was determined to be 83 % pure by GC and I H NMR. The crude

compound was loaded onto 60 g of silica gel and eluted with EtOAc/heptane (3/97, v/v). Fifty-

three fractions (8 mL) were collected. Fractions 1 3 to 50 were combined and concentrated to

yield 0.2460 g (74 %) of a clear, colorless liquid product that was determined to be 97 % pure by

GC analysis and IH spectroscopy. IH NMR: 6 1 .66- 1 .76 (m, 2 H), 2.28 (S, 3 H), 2 .33 (s, 3 H),

2 .52-2.6 1 (t, 2 H, J = 14.34 Hz), 2.76-2.94 (m, 2 H), 3 .74-3 .79 (t, 1 H, J = 7.37 Hz), 4.96-5 .06

(m, 2 H), 5 .64-5.74 (m, 1 H). 7.0 1 -7.25 (m, 4 H). l 3C: ( 16 peaks) 6 1 95.6, 14 1 .9, 1 3 8. 1 , 1 3 5 .4,

1 28 .4, 1 28 .3 , 1 28.0, 1 24.9, 1 1 6.9, 49.5, 40.9, 30.6, 29.8, 29.0, 28.0, 2 1 .5 . HRMS-EI (mlz) : �

calcd for CI6H220S2Na, 3 1 7. 1 0 1 0; found, 3 1 7. 1 028.

Synthesis of 2-nonyl-l,3-dithiane (MJS2113crude)

o H

(l SH SH ( 1 .8 x)

CH3S03H ( 1 0 .0 mol %)

CH2CI2. O oC

S:) S

A solution of decanal (0.5662 g, 3 .623 mmol) and 1 ,3-propanedithiol (0.6 196 mL, 0.6666 g,

6. 1 69 mmol, 1 .8 eq) in CH2Ch ( 10 mL) was stirred at O °C in a three-neck rbf as methane

sulfonic acid (0.024 mL, 0.035 g, 0.36 mmol, 1 0.0 mol %) was added. Reaction progress was

followed by gas chromatography. After 1 8 h, the reaction mixture was stirred with 2 M NaOH

60

(40 mL) for 20 min. The mixture was extracted with CH2Ch (3 X 20 mL). The combined

organic layers were washed with H20 (2 X 40 mL), 2 M NaOH (3 X 20 mL), sat. NaCl (40 mL),

dried (Na2S04) , and concentrated to yield 0.6959 g (78 %) of a clear, colorless liquid that was

determined to be 97 % pure by GC analysis and IH NMR. IH NMR: 6 0.80-0.85 (t, 3 H, J = 6.9 1

Hz), 1 .22 (s, 1 2 H), 1 .36- 1 .46 (m, 2 H), 1 .65- 1 .87 (m, 3 H) 2.03-2. 1 0 (m, 1 H), 2.6 1 -2 .84 (m, 4

H), 3 .98-4.02 (t, 1 H, J = 6.67 Hz).

AHylation of 2-nonyl-l,3-ditbiane (MJS2U 7fr1519)

s� s

�SiMe3 (1 .7 eq)

AC20 ( 1 .7 eq)

1 0.0 mol % Bi(OTfh O oC

o s�s�

A homogenous mixture of 2-nonyl- l , 3-dithiane (0.2522 g, 1 .023 mmol), allyltrimethylsilane

(0.2764 mL, 0. 1 988 g, 1 .740 mmol, 1 .7 eq), and acetic anhydride (0. 1 644 mL, 0. 1 776 g, 1 .740

mmol, 1 .7 eq) was stirred at 0 °c under N2 in a flame-dried rbf as bismuth(III) triflate (0.0671 g,

0 . 1 02 mmol, 1 0.0 mol %) was added. The reaction mixture immediately acquired a light yellow

color. Reaction progress was followed by gas chromatograph. After 3 h 30 min, the reaction

mixture was loaded onto 60 g of silica gel and eluted with EtOAc/heptane (3/97, v/v). Eighty-

eight fractions (8 mL) were collected after a 50 mL prefraction. Fractions 1 5 to 1 9 were

combined and concentrated to yield 0.2 127 g (63 %) of a clear, colorless liquid that was

determined to be 97 % pure by GC analysis and IH & BC NMR spectroscopy. IH NMR: 6 0.83-

0.88 (t, 3 H, J = 6.67 Hz), 1 .24 (s, 14 H), 1 .3 9- 1 .58 (m, 3 H), 1 .79- 1 .85 (m, 2 H), 2.27-2.32 (m,

4 H), 2 . 5 1 -2.64 (m, 3 H), 2.92-2.98 (t, 2 H, J = 7. 1 5 Hz), 5 .02-5.08 (m, 2 H), 5 .77-5 .87 (m, 1 H).

6 1

1 3C: ( 1 5 peaks) 0 1 95 .6, 1 35.7, 1 1 6. 8, 45.3, 39.3 , 34.2, 3 1 .9, 30.6, 29.6, 29.3, 29.2, 28. 1 , 26.7,

22.7, 1 4. 1 . HRMS-EI (mlz): � calcd for C1 8H340S2Na, 353 . 1949; found, 3 53 . 1 963.

62

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69

IV. Appendix: Spectral Data

70

rJ1 "d � � ..... .., = = ....

:::r:::

� o >-+, � [/1 tv o VI -....) ::p tv o VI .......

�l

x 'E a ;; .. "" � o· := '"' ::tl

7.5073 7.4780 7.3947 7.3022 7.1053 7.0989

5.8636 5.8379 5.7995

5.0742 5.0375 S.01}37 4.7079 4.6978 4.6795

.... g

)0 ' o

�

�'C . __ r. "

. ...--'"

/;c� ;",

� ''-...... <:) -� .... ,/"

" ', " U. / ' /' Q

", ;'';''

/ 4.1804 '-... 4. 1 566 4. 1 328 /" ... ;",

�:�:g� ;>�i 3.3388

2.4377 2.4194 2.3928

1 .9899 1.8883 1.8654 1.8425

0.0549

�

" .... :';'-' "

...... N � ........ �. ,b " //.

..... ;", -

0 -'

,_ • .. -

(Millions)

o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1.0 12.0 13.0 1 4.0 15.0 16.0 17.0 18.0 19.0 20.0 2 1.0 22.0 23.0 24.0 25.0 26.0 27.0 .J..tJ .. t...t.. J...d • .l.L.I...Ll..t..u..1.LJ.L.Ll. LLLt.LLLl .u.Lt.u..L.l.l.l,.l.. d . .1.Lu.l..l.1.I...LJ...Lu.JH1J .. �1.d_L...Lw .. l..r_w. • .d.J�� .. l,J�Lu ... u...LI..L.I •. .d ... UJ....lJ...J...w.L...u....t..1.w.L.l.,1.J ... ILL.1.J,..t.l.J..w...L.lu..LLlLLW.J..)..L,.I . .r.�

j 1 co .....

o )=0 (�- -----

_ .. _ .. _ .... "'----�

-\

�� [ ---�-----·I r·=iffiiE· ····,,======----- ---------�

I

[��----.---------. �

L-T

�---------.

� til ..... ::r tv 8: ;1: ..:.. !?;;

�

t"'57f"'51��2'" o � 0-] 8 �

i ,i-,'-"'TI "', ;"""", ,.., '"', ,'""""'TI " . . ,-y,"", ,-' ,.." ,,",,T' rl n, ,-,.,,..,,.., ,M'''''''' "I '''''T''''' n. '''T''''' ,.., (,",'''''''' n. ,,,,,..,.,,-, '" ,'"""'" .... , ,M',",,"" "" ,,,,..,.,.,-, """,..,..,..,-., ''',,",,, ,.., ,",, ,,",'T''''' n. ''T,T''''' ,.." ,,",,,T'''-, ,n,'T,"" 'i"" ,,.., .... ,,.., M, ,-r'ITT'1 .n,-"''''' .,.., ,""'-"'TI MI ,n,..,., ,.., n. ',"".,.., r, n. ''"1''T' .,.., ,n,..,.,"",,",,,,,,,,,,, ,,,,,,,,,,,,,,,,,,,, n[ ,,.,,.,.. ,.., n. 1M,""' ''''' n[ i"""', 'r' .r.,,,,,,,,,,. ""1 11"'1'''''''''' ,"" ''''',"",,.., ", ,,'T' .... , ,M,.",,.., n. ,nl"'''''' M. ,-r'T' '''', .n'''''I''''' ,,", ,"',"" • .,.., ,,,,.,.'TI ,-,. .. 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 no.o 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 2,0.0 10.0 0 . '., i \'\

,� - M <:> - .... <:> M - "' <:> .... .... Q "" .", l"- _ � ::::; ':1 .,.. "" QO l"-"'; N o:S � M � ::::; !:! � � :! �

.... '" '" III N <:> ::: � til ,.., Co 1.0 � "" r-: :l "" :g "" .... "" "" N N

X : parts per Million : DC

Spectru� 2 l 3e NMR ofMJS2057fr205 1

<J) 't:I � � ""! 1:1 = w ::r: � :;;0 o >-i") � r:/1 ....... ....... 00 Vl

� Vl o 0'\ \0

�

"<:I ,. iii> 16 ... � 0 = ,... �

(Millions)

: 0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 n.O 12.0 13.0 14.0 15.0 16.0 17.0 18.0 1 9.0 20.0 21.0 -Lu...l...l-Lw ! t I . j ! J I ! . I I I . ! I ! ! t I ! ! I . ! ! I j , I I I 1 1 I f , I , I I r I , ! I t I f I r , I . , J I f I ! t ! ! . ' I ' I ! , I I I , I I ! I , I , t 1 1 I ! t I • • ! . ! , . 1 I !

,; p

7.4524 7.4213 7.2464 7.1438 7.1136

, "

'""' g

�

�

............

.... _-.....

---... � <:>

� �'�i:� �� 1 � 5:6886 ?-- = 5.6529

::::, '" .� L. l 5.0055 / .<:\ ( 4.9625

4.1493 �'" 4.1255 7"'ot. 4.1016 b

3.3269 �,.:.; 3.3132 7"" 3.3040

2.5265 2.5000 2.4743 2.3434 2.3177 1.9771 1.8590 1.8361 1.8132

w <:>

�;� ?�': .......... !" >fjQ

1.2317 --. . ... .

,.. <:>

c:>

......

�

OJ .....

� o /=0

"I

-,

! .... � ::;0 ,.

! e;

mjs1185frac5069car-2.jdf

I I �O.O ,' 70.0 60.0 50.0 40.0 30.0 2p.0 10.0 0

/\\ 200.0 140.0 1l0.n 100.0 130.0 120.0 190.0 180.0 170.0 160.0 150.0

r--- tf"I � '>C N '" o.n o.n '" o ....... - t--- ... '" � � � - Q � \C o.n � '=' 'O ''''''' \Q � "" 5 .,..; � t--= w vi ... M '" C/C t"-- t-- I:'"-- \CO \CO � N N

X : parts per Million : 13C

Spectrum 4 I 3C NMR ofMJS 1 1 85fr5069

mjs1185fr5069dept135-5.jdf

� I

200.0 190.0 180.0 170.0 160.0 150.0


I 140.0

N "" .". M ..,; :;

130.0

'" '" tTl "" .". 1Il :2 ,.. 00 :; �

I ' 120.0 1 10.0 100.0

.... '" .... .., � �.

I 90.0 80.0

.... <::> � ;;

Spectrum 5 DEPT- l 35 ofMJS l 1 85fr5069

70.0 60.0 50.0 .40.0

"" '" tTl "" '" "" :! "" '" � -..; � '" "" ."

30.9

." ." tTl '=! "" N

20.0

\to '" '" ;; N

I 10.0 o

1 ; �I � �j � 4 t

! : [

, '

, ,

: �.l; i

�'�l '�"�"�'�l '�"�' �"�' I�' I�'�jj�jj�t 1�'�i j�j(�j j�' �" �"�I '�"�'�"�il�' j�'�li�"�l t�' �I I�j l�I I�'�iI�"T! I�' �ll�"�"�' �I I�Ii�\ I�' �ii�I I�II�' �"�"�"�I �li�Ii�"�' �l lnj l�"�' �i l�"�" �" �'�"�"�"�J �"�"�i1�'�l 'nj l�1l�'�j '�l j�' j�' �" �i J�' �ii�' l�"�' iI �i �� 170.0 160.0 150.0 140.0 130.0 120.0 1 10.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 100.0

X : parts per Million : l3e (Thousands)

Spectrum 6 HETCOR ofMJS l 1 85fr5069

00 "'0 ee � .... ""i = :3 -...l ::r: z � o >-i') � 00 ......... ......... -.) \.0 ::p 00 o \.0 \.0

x

't) ., it � � § iii

" "-.

-p -<::>

�

� �;

7.2976 7.2665 7.1978 7.1 658 ;> --I Q

5.7546 "-,,-5.7189 .

5.6886 , .. -;; .

5.6529 ./

'" Q -

5.0174 � .. !" 5.0018 / .:Q 4.9588

4.1483 -, 4.1245 -' .I>, .

4.1007 ,/ Q -

3.3342 "" 3.l2S 1 /" .

3.3123 r' w b -'

2.5027 " " �

2.4762 2.3461 ,..-"'..-2.3196

1.9725 �'" l" 1.8590 " '" c 1.8351

/;�. 1.8[23

,... Q

0 ·"

(Millions)

o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1.0 12.0 1 3.0 1 4.0 l5.0 1 6.0 17.0 18.0 19.0 20.0 21.0 22.0 23.0 24.0 .1,J..LI.l-LI.J.J.J..f.Ld-.l.,L ... ,�.l,u .. 1,J . .I..I..I,.L.l-L1..u...Lll...LL...J_L.J...l.l_Ll.J.....L_l.L....l_1..J.,.L'-t..w.J . .L.J. • .l.J_l.1.J.J_I.l.,1,.L,�.J�J,.t..t.Lt.l .••• .u. . .LLl.l...L.-l.l..w....t...t..L,J..,.,l....l..l.J..t�wJ..J...w. . .t.L1...L.J._.t...l....t...U • .LLL..w....t.

Q

1 o )=0

�;.�' "W'h

--��-.,--� .... -.-�--•• ---.--•• -------------------l

�I COC=· . ----·-··---·-----""'-�··-........ �_. __ .��N_�. ,--� ... ,� ......... ,

.. .. _-_ .. __ ... __ ... __ . __ ._ ..... _. __ . __ .,

�--..... --� .... __ ._--"'"'\....

L= -.. ----.----.. -�

----------_.,

2. '" ..... ..... � ;i' &, J 'a: ..,

�-;�,�: .. -" , --------=--_ .. _._

. __ . __ ... _--'-----)

L .. �.��,�. __ '._.M._.'_ ._._._.,._ ... _____ " .. __ .... �_,_ .. _" .--. .....• _��,_. __ .• _ •. , ___ .,� ..

I'-II ! . I

j i " i l " " I " " " " I ! I I I " " " I " " " " ' ( " " " I I ' 1 , , 1 , • . , 1 ' 1 , • . 1 . 1 " ' 1 , . , . , , 1 " " " " " " 1 ' " " " i 'X" " " " ' l " " . " " I ' · ' · ' · " ' I " " ' " · ' I ' . " . · · I · l " ' · , i l i l j • • • • • • • . . j . l • • . i . , . j ' . , i . . , . 1 1 1 " • • . , 1 ' 1 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 1 20.0 . 1 10.0 100.0 90.0 80.0 . 70.0 60.0 50.0 .40.0 30.0 20.0 10.0 0

/ \ ,... M ... ... ... - ." N '¢ � O\ ... ""

l§ <::> <>- '<> ¢O N .". t- N QO N M '" <>- ... .., 00 "" <::> V1 N "'=f OQ ;:: Q\ "" C'l "" <n O 8

f,(') ,¢ - '¢ "< E d � M 00 00 ...: � � � vi G :::: � � !:"! � 00 t- l.""'-- l' ""

-

X : parts per Million : l3e

Spectrum 8 I3e NMR ofMJS1 1 79fr8099

m,I!!20S1fr3052-4.jM

I' .

.

,--

,--

i-J

0

O�O� ~ r r

i

f j� . ..1 t j'J�v 1 ...I.! • J . ...... 10.0 9.0 3.0 7.0 6.0 /1\ 5,q 11\·0 3.0 :t? ,\ 1.0 , 0 / ;\

� ' lit 1\' '1 \ j 1/ \\ j;\ /11 I , , l \ I ;

�¢'\"'$ "' .... $ " .., .., ii�g ")It> '" !'"'''S; .... .... .." " i � t! � ��" !�! "' ... ... i�"'= ", ,,, ... g;::! ... �;:!;:;:: .... .. ,.. "l"l"l "l "l "l "l . .� . • �..¢'lf!�"". � . il' ... .... _ . � ":"'lft.tdi.n ...t V � "' ''' ''' N N N <"l ...c ..,c ..... 'I'!"'l <l>

X : jIIlI1!I per MiI&Ja : 18

Spectrum 9 IH NMR ofMJS205 1 fr3052

mjs20S1fr3052car-2.jdf

o O�O� ~

°NM�� '�' rl .n" '�'�'�' MI Ln" ,"T' �1 1�'n" " " 'rl n"r..""T,�. 'n'n1"T'rl .n" " 'T'�' rl ,n" 'T'�' r. ,n" " lr, n' in" 'T'T'r" �I" •. r'T. r, .n" " 'Tl r •• n" " 'T'�' rl i�I".'�' r' in'n" 'T'TI M. 'n" ,.,r,r •• n'nX".,r, r" M" " 'T" j ,n,n .• " ,r, n, .M'nl.,r,r, n' In, •. T'�' ni .n, ••• ,r. n, .n" '., T'r' nlt".'T. r' M. ln· ••• " 'r,IM'n.,.""r,.M" ,.,.",r'jn" ,r,r'T'n.'n" " IT'rj.n.n" 'T'T'�'!n'n'T.�'�'n'·""T,r'n'.

200.0 190.0 180.0 170.0 l60.0 150.0 140.0 . 130.0 120.0 110.0 tOo.o 90.0 80.0 . ' 70.0 60.0 50.0 . 40.0 30.0 2,0.0 10.0 0

/F 1 \ i\ / \ � "I!!f" 1:'"-- 1:' co t- � _ 'd" O "'l:t '" "., "C W - ",," <::> r- "., Q lI'l _ ,¢ ¢) � "., N r-: r-.:"&i ..". '" <;o r;--. :r;--.. t:" "" "" ..".

);; ,",," .,., � � � :1 � '" '" "' .... X : parts per Million : 13C

Spectrum 10 l 3e NMR ofMJS205 l fr3052

CIl "0 � t":) .... ... = = .... .... ::r:: z � o >-l') � CIl ....... ....... \0 ....... ::p N +:>. W W

�

'g it � is: § g s

7.2583 7.2280 7.1996

6.8489 6.8187 6.7821

.... <::> ¢

� <::>

r;;

�.,," / -..) ¢ , --

/'"

""

5.8040 ¢

5.7665 � -5.7408 -j : 5.7024 /'

5.0495 ,_ Ul 5.0092 - .-.'�; ¢ 4.9744 /'

4.1621 � ;, 4.1383 / .. .... . 4.1145 ¢ '

3.7903

�:�� §! 3.3251 /'"" 3.3031

w ¢

2.5220 �,�, 2.4954 ------;;'" 2.3754 /''"'

, 2.3535

1.9808 � .. !;; 1.8718 �'" 1.8480 7--:" 1.8251

... ¢

<::>

(Millions)

o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 1 0.0 11.0 12.0 13.0 14.0 15.0 1 6.0 17.G 18.0 I' ' II ! , t ! 1 . , . I w...l-J ' 1 , t I J t , ! , ! ! r ! ! ' .L.I.R��l....L-1-l....l-..t..J ! t ! , ! . ! t I ! t ! 1 I I ! j . " . 1 " , J ! I ! ' / LJ.....LJ.....l.l..J.-t..I-l....W...1.. .

�

o o I V>

L· �_. ___ � ---"::::zss=

c� I

�

1 o (=0

I

")

.E. ::: :::; fS ... J, 1 0. ..,

--I

i c: '" :; s E-

� '" j j J o j ..;-] .... ' j i

3 "' � <:> ..., _ 1 �

� o::>

o O�O�

~ OCH3

' t . , ' j • , i I • 1 . , • I I •• i , • • • , I ' • • i I I , j l, • • i • I. j , ' i ' . . I l i t . j I ' L j , 1 i i . , [ I • I, t" , . I • t I , I. , . • I •• , , i •• , i l' . , I i . , • -:l' I , i , I i ,j { j • • , I . II • t j i i ' i • • • • , •• I, , ,j • , \' . , i i , i i , ! [, . . • , ' I . i . . • I I " t . j I I • I • t i t . 1 I . I • • • I I I I' I , j j . , I. t 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120,0 HO.O 100.0 90.0 ,80.0 " , 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0

� .... "" Q ....

5 � .,.. . '"

"" ..; :::: � .� X : parts per Million : Be

"" to "" .... "" 00 <:0 .... <:> "" .,.., "" '" <'l - '"

-.i � � � :::l ;::: - ...

/ \ 00 <'> 0 '" _ N � ¢! � �

! J/\ .

Spectrum 12 1 3e NMR of MJS 1 1 9 l fr2433

rJ). "0 ee � ..... � e ..... f.H ::c: z � � o >-i; � \./J N o Vl \0 � w � 0\ w

� .. 1 � s: I§ § ill

7.2454

5.8022 5.7756 5.7381

... �

g

00 <:0

.... (:,

0\ (:, "'-... .. ;;;:.::

(Millions)

o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1.0 12.0 13.0 14.0 _, ! I ! ! " ! I ! . J 1 ,I ... u ... L.WJ ... LLLW..1.J . ..I."UJili.l..U .. LJ..l t ,1 , . " ! ' ! t , ! f f ' I ! " t j 1 , LJ...l..l..LLu..l.u...u..u..w..w.J.J.J...U I " ' ) ' t " , ! " I I , ! , ! I l f .wl..w...t�.! , I , r t ! , I ! ! ! . , ,� . �

�

i .:... e;

� o )=0

5.0678 ''-.'"

�:�m ;;: ·(:,1 r-·---1

4.1648 '---" 4.1410 ;'/."f>

4.1172 0:>

3.5137 ':::-::i: -�--l 3.4908 > i F 3.4597 /."., 3.4368 / _. 3.2482 �

'----

;:::;,� 2.2445 2.2188 2.0256 1.8745 1.8507 1.8278

1.4386

1.2408

/" �-... (:, 0.8818 "'-,.. .

0.8580 7 ' 0.8324

0.0485 0::>

C -�l

=�

r.f1 "e � � "* .., = 9 .... ...

w (J

� o H") � r./J N o Vl \0 ;:p W ... 0\ W

x ] a � a: f -'"

t-.> c ? c

.... \0 ? c

.... co ? -c

("J 171.1737 .:::; c

135.1666

1 16.7850

<::>

.... <!1> ? <:>

... ;!l -C

� � c ·

,... t-.> ? C

g

C; . gl-: "" ? <:> •

79.3492 � � 77.5691 "'-. .:c 77.0955 7 ' . 76.6294

65.2536

61.9149

�

' <!1> • g

� Q

� 38.4068

._v"' . ... �=

33.9222 -... . 31.9816 ,-.. :--- '

. 29.8348 ---' � Z9.6743

. 29.7049 �:'b 29.4375

...

29.4070 � .N 25.4647 r"? 22.7602

<:>

21.0565 14.1958

-,-.... ? -c

Q

(Thousands)

() . . 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 100.0 HO.O l-L.LJ...LJ_, • .l.J.J . .LL,...L..i.-L..l.ll.l j I , ! ! t , 1 ! • I , , , ! t ' I r " , " ' " f • • , , , I ' , ! I . ) ! f ! , . ! 1 I . I I t t ! ! ! , I • • • ! , ! 1 I ! I , t t ! I ! , ! • I , ! , ! • , , ! ! I ! ! I I I

1 ° (=0

.§. � cr; "" 5; t fiJ � l c � ...,

00 "0 � � """ ;:! 9 ..... u-. ::c:

� o ...." � r:/1 N ...... o -..J � ..j:::. ..j:::. 0\ o

x ." '" � � � = �. =

7.2454

5.7573 5.7354 5.6960

5.0852 5.0641 5.0238

ii> . Q

:.c <::>

co 0 '"

;-l <:>

g; '> . //

'-. . , > 'tit /' C

4.1483 "-. .. . 4.1255 ... . .. .. """ 4.1016 /" 0

3.4972 3.4817 3.4734 3.4606 3.4377

2.2555 2.0210 1.9377 1 .9267 1 .8745 1.8516 1.8278

�.: / ..., o ·

� . � � ;; .... o ·

¢

(Millions)

o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1.0 12.0 13.0 14.0 15.0 16.0 17.0 18.0 ,-..tJ....,�.L...L.I-j • ..I�.J..J ... .J_LJ._L..I._l�lh.LLL_LLL....l.._Ll,J..J.....l..J._J.JJ.JM.J�.J • ..l.J_J •.. Lt.....L.LI�LL..LL..1.......l.-.Il_.l.....t�l-1-l..i ... LL.J._l......L..LJ.. •• t_l.,.L..J I ! 1 I • • • I r ,_.I,_Ll-J_W_,LL..L.J-.l-L.J.....J....l..

� �� L __ _ � .�:=-

"

--�

OJ ....

IJ 1 ° >=0

... ---.-.-.-.. ------.---------�

��.-.. ----...... -� { -- ----$if-

E. � "" ...., ::;-....

1 9;

.. -�

" -!mjs2107fr44-6o-2.jdf gl

." .; .:$-1 - 1 � -1

o O�O�

Br�

,

C> __ � __ �

I i �·.�' rl �. 'n,�.�,�. �' r' inl�'�iT'�' �I .ni�j�'Tir, �, .n'�'T'T'r' �) {r..�'�'�' r, rj ,r.'�'�lr'r' ri jn" " 'T.r' rl jn,�" ,r'�' ri jn'n.,'r,�. r' .n.",'r'rl rl 'n" 'T'r'r' r.' lnl"T'T.�' r, tn.n" 'T'Tirt in'n','r,�,rjI�'n" 'T.T'r . • n,n" I,.r.r,r'in.""T'rlr,.n'r.."�'T.r'r"�" " 'T'r.r"n'n'""r.rl.n,n" ,r.r.r:.r..""r.r.r.,'n" I�'T.T,r.r.,.n'T" 'Tjr'rjln.n" 'T,r,r'jr..n" 'T,r,r,r'IM" ,T'T'T'r,.n'T,T.T,�.rr"

200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0. 3"." 20.0 10.0 0 / \ I \ ! \ I

i \ '" t- � � � t- o. '" on 00 '" "" on <; "" "" ..... ... - 00 <Xl ..... "" ..... '" "" .., _ on "" '" .... <:> ..... "l ""': � "l "l � � � f'P) "'! ..; � . , ..... r- "" � � oo t- c:> e. -

::l t- t- ..... ,., ,,, <'> '" '"

X : parts per Million : 13e

Spectrum 16 l 3e NMR ofMJS2 107fr4460

00-� � � .... � 9 I==' -l ::r: � :;;0 o I-+) m ...... ...... tv W

� -l � W

><

1 � i 1:1 "

.-1;

:.: �: �, ! = ;1 - �

�

7.3004 7.2692 .... 7.1850 ;.,/ "l 7.1539 0

0\ <:> 5.7903 �._. 5 7546 '-'''-',.:: 5:7244 ;/'" 5.6886

5.0192 ::::::" .� 5,0055 /.- . 4.9615

4.1410 4.1337 4.1126 3.8864 3.8782

:::::"" " / � ?c ... :

3.0265 ....... -.:.:� 2.9780 ;;::: ''''' 2.9460

2.4780 2.4496 2.4249 2.3452 2.3187 2.2976 1.9890

1 .5879

. 0.8992 0.8763

0.0549

............ ..

��:� j ' N / ' 0

....

'_.-;,,,}::>

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(Millions)

o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1 .0 12.0 , " ,I ' ! " " I..J..J...l..J..J..L..LJ..t.J..I ... t..l . ! f l • • • " I • • , . , . " . I , · " " , ' t ' " " f l " ' ! " ! I ' ! " ' ! " ' ! ! I , ! , ! . , ! , . , . • . ! , . , ! . • ! " I . ! t ! t l t ! j l • • , . , . " ' I I I " �'

C;! '"' .... el l:I' Il1

o S - L t ... e;

o ff� o /=0

�._ ·s ________ ......

�.::. ----7

---l

-I

-�

..... -= � " <:> �

EB1123fl"l'lc37-43car-2.jdf

"" .;; ""

Q .;; .....

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"" .;; on

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Q .;; ,..,

i J J

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: i I I t ' • I , • • I I ,1 [ • • , • I , j , t , I i i i , , I ' j • , , , , , • i ' l , • i , j • • I ' • I • • • I • I I t , • , .1 . l • t t • l I , i i , • 1 t •• l • • I , , I I , I i i , i ) IJO' • i J , • • I i I • l • • • , • . j I • . I t . , i I \ J I , ( • 1 . • , I I . • , I • , , i • i i • • • j •• i i i ' . i • • , • , , j • • • I I . I I I I ( I i . , • I • [ I J • , • • • • • , I . 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 1 10.0 100.0 90.0 80.0 .... . 70.0 60.0 50.0 . 40.0 30.0 20.0 10.0 0

"" '" "" 5 :!


e-. "" "" "" 0 "'" "' -� M "" "" ... -

i, f \ , ,

", e-. ... "" - "" >0 O Q6 06 "'" '" - ...

Spectrum 18 J 3e NMR ofEB l 123fr3743

, \� " i ! \" '\

(Millions)

o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1 .0 12.0 13.0 14.0 15.0 16.0 17.0 18.0 19.0 20.0 2 1.0 22.0 23.0 24.0

J f ',I . , ! . I . Ll..t..l...w...1.J..LLI_.l_d_.1....1_I...w..J...LJ.J..lu..w..L.t..J... I.J...l.J •• LJ.J..LJ.., ... l • .t-i.LJ....l..-,I....l....1...L�u..L..Lu....wJ.Lw • I • • 1 ] r , , • , ! ! I ! , ! t , I I I ! • , ! I , ! , t ! , r ! I ! • , r , I , ! , , I , , ! ! at I

:><! 'g a � :.z: E g iii

.... � -

�

00 o

,g' 7.2445 eo 7.1365 � a � = e

,... \0 ::c

� z '.M" � . [ � ':7 5.8077 -< �

I ,:::.,

5.7821 "/ � 5.7436 o H-,

� ---I <-< 5.0430 = -'-

I C/l

5.0064

I N 4.9716 o

0\ W ::p ........

� o )=0

8 f\.1456 � , 1 C--l. . . �

" 4.1355 // !>-..-�:;��i /' Q [_ ••. =_.

3.901 1 .

3.104: '::,"w c:' -- ==-'-- ____ '\ 2.9789 / .. ")71 •.. • � . C 2.""

. __ � 2.5339 �.'. '." C;; '-=-2.5064 '.r-7 .... 2.4789 /J:;.: (_

. __ , 2.4533 / /

\ 2.3645 N 2.3370 ..... 0 - r 1.9945 -

0.9111 0.8901

.' 0.0769

:-' '--. Q ----.-

""

I-

:j

'1;; ' � l:l � j c., ...

�

16M 1S0.0 14().0 13(),O 120.0 I 1 1{l.() 90.0 So.o . . . . 70.0 60.0 50.0 40.0 30.0 211·0 10.0 0 1 /'0\ \ /!\ , ; :

2(1);0 180.0 170.0 190;0

..,. ... .... 00 0 "" 00 'C 'C O\ c:> o.. 00 .... .... "" -- - eo- - ,", .., 00 �n� � � � 0 on 00 0\ 0 "" '<> - <'> = �:, N "" '<> - <'> "" on "" '" "" '" .t'<,;.' .... ,.,:::;; � � ;::!� � � <>') "": "": � � c;:: t-= � ¢: -6 , . ...o!.,. .... '!J '" .... ... = <'> <'> '" .... .... "" ,-('., � ... � ..... � �'.� 00 t'w l""-- t"-- I:""- 'o.O '" "' ''' ... - .-< - - - '"'

X : parts per Million : Be

Spectrum 20 l 3e NMR ofMJS2063fr1034

iJ1 "0 � � ..... '"'l = = N i-' ::c Z � � 0 >-+-, tr:I b:i ----tv Vl i:t' \0 --0'\

:><: . . ." .. a � is: f s

... g;

�

�� 7.2464 .. . . ...

� � �

0\ � .. 5.7930 5.7674 /'" 5.7299

5.0467 '-...... . '" . 5.0156 /' � 4.9780

"'" � 3.8654

3.2253 �" 3.1932 3.1218 7 -··� . 3.0897

2.2234 �." 2.1978 /" N 2.1758 /'" .. �

2.0339

1.5943 1.4176 1.2829 1.2408 ..... --�---

0.8956 '-...... .. � 0.8608 -... . ,,'" 0.8351 /'

<:>

(Millions)

o to 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 11 .0 12.0 13.0 14.0 15.0 16.0 17.0 18.0 1 9.0 20.0 21 .0 22.0 23.0 1 • ..t..LJ...t..J • .w . .w�w..l.WJ. .. d . ..t..L.I...L.! . .1...1....L...LL,l . .J • .Lw..w.J"i . ..l..,-d-'-1.J,...t..1.1 .. Lw...LJ_J_J.J...LJ_.LL.l I ! 1 , ! ! , I t W .. w .. w .. .LL.LuJ..J....l...J.,J...L w...l 1 I I ! ! , ! t , ! ! f , , • , I , w...t..l..u..w...Lu_.u.l..

trl I;!;I

I

I

0 ( � 0 (=0

.... .... ..., '" ;r 'f' .... "" -g (ll 1.. � .."

---�-��=====-------------------------------� ----;

00 '"d � � -'"'l = 9 N N

w n Z � o >-i; tr:1 OJ ....... ....... N Vl � \.0 ....... 0\

><:

'g al � 8 ,...

tv

� ... "" 1; ....

g

)l) 171.0896 ,... ...:t .

, <::> "<:>

� ....

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135.3042

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1f6.4870

,...

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, 76.6523 / ...:t 74.5361 69.9139

p C> "

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38.2922 �

35.5265 ......... <::>

33.8076 ' " 31.9663 --" 29.81 19 . .;' � 29.6973 ?';"<:> 29.6591

.

29.3917 % 25.3654 ::; '" 22.7373 ?l P 22.0573

<::> •

20.91 1 3 14.1576

... --....

::; "<:>

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(Thollsands)

o 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 100.0 1 1 0.0 120.0 130.0 .�., . , ! • • 1 . " • • , ' •• L.J .. Lt..LLWJ..LLI..lu...w..w-U."L..!...J..M .. w..u.L..U I I ! ! 1 1 1 , 1 1.J..I..1.t....w..l.I-U . .L1 , ! , I I " I I I ! ' 1 . 1 I I " ! ' I I I J I t. •• u ... u_u ... d..l.J..L.I..I..1..I...L.I." " I ! . I . ! t ' ! ! ' " I ! ! I

� 51 ;t ! g-

� a;

� o )=0

rJ) "0 fj) !':) '""" "1 =: = N W tI:

� o >-+, � C/) N o -.....l ....... � ....... ....... W Vl

>< 'E � 1 ., � § =

.... g

�

00 e:,

7.2985 � . 7.2839 ;;:: .. 7.2436 �

� 5.7015 � . .

(Millions)

o 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1 .0 12.0 13.0 14.0 15.0 16.0 17.0 IS.0 • , I I I ! 1.-'-.l.�.J�L..1..J...J......L.l....t...J....L.L..i • ..1�l..J......i-J ••• LL.L.J._L.,r�,.l-J�.! •• LJ....L.l�l.,.L.I ... l .. .i-•. L .. Lw ... I-L..LLJ I , I , , t I I • t 1-�.L......l...I-.l.J,�I_.t....J."""�L • .J....J-.

II 1 (f) )=0

a. :-;.. s .... 5: .... � J. �

(

5.6758 7::· : I I -I 5.6383

5.0467 ------• . /Jl 4.9890 "-'''' :.:;:' 4.9524 ./

" i � .-�

3.8352 � . 3.8068 ;;-3.7793

"" e:, -

?' �" o 2.8516

2.8214 2.6145 2.5879 . 2.5604 ./ 2.3177 2.2939 2.2720

.,�. "-

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;;

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[� - �'---------.

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C -=-== ,- -----:--�o:::ca="""' . . 2!t!Q:z:�. � __ -[

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mjs2071fd 135car-2.jdf

o S�S� r

" ' I " " " " ' I " " " " ' I " " " " ' j " " " " ' I ' . 1 . , I I I , I [ . I . , , · • • I . · •• · [ · . · l • • • • • • • , .] , . , I I • • • • j " . 1 . 1 I , 'I' • • • • • " . I I I , ' I , ' . ' I " • • • · . , · I · I , . I • . · · I " ' . · ; , •• ! • • • • • • • • • I ' . ' . " • • 'I •• I . l l i l , ! " I I " · " I ' · · ' · " · ' I '

200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0. 120.0 , 110.0 100.0 90.0 80.0 ,: , 70.0 /1\ /:\ ... � 00 00 "' "" 1;cl "' ''' ''' '" '" � � tt "' ''' ''' on '" '" '" ", r-. -"'l '" M <0 <:1\ .. '" � � � \f) � vi 06 r-:: r--: � r-- r-- \Q

:�.� � "' M '" r-- r-- r--- - '"' -X : parts per Million ; Be

Spectrum 24 J 3e NMR ofMJS207lfr1 135

60.0 50.0 �.O !

00 N "" '<> "" "" '" "') "" ." ... ..".

39�P 20.0

11\\ � ('t") '¢ "'" U') (/') Q\ f"'l Q \C- t") N r-- oo -,....( .... c) � c\ OO ('f'} � <"l '!"'l

10.0 o

i ! l -"-'7" '�"" :---'-" '-" -" ''-'''�''--- ,.-�

(Millions)

o 1.0 2.0 "

. d

3.0 4.0 5,0 6.0 7.0 8.0 9.0 10.0 1 1.0 12.0 13.0 14.0 IS.O 1 6.0 17.0 18.0 19.0 20.0 21.0 22.0 23.0 24.0 25.0 26.0 27.0 l l lll • • • • ! . , ! ! 1 ! · , .sJ-t...u..l�L1.W ... ..d 1 . ! , l " . ! 1 1 1 1 . ! " " I . , I , I " " I • ..t.J..J..i...u i , t t . I . , • • I • • , ! ! '�.J I , ' I . I • • • . I , ! , . 1 . , [ , 1 , • • • 1 " " I t • • • f t ! 1 . 1 . , . , 1 . , 1 . ' , I..T

) �

1 � ;;: 5: 0' = .... ::t:

.... ' <:> ¢,

�

9" <:>

Q

en

� � en )=0

7.2876 "' .� 00 7.2564 7:'" ..:=,....,,;;;:;��"'"""'======--===�-

'e 7.�354 '-l � r -r f'D . . ¢, � '\ ; 2 ; : 51 ( ;: N til ::c: g; z

o H)

� �:�m >: : J � :::0 5.5989 / L � 5.0284 " , ?, C;i:l 4.9927 / I;> .--� ---"-,.----.,

tv 4.9579 / I I

o \0 -....l � I-' W W ..,. � ¢,

3.8104 '" 3.7820 " , .

3.7546 ./

2.8553 .2.8223 ·2.5522 2.5339

, . 2.3104 2.3013

' 2.2839 '2.2573

!" ��r �o-,

):; '" ¢,

1 .7289 '->,,'.; 1.7024 /-' 1.6758 l .2344 -

¢, -

<::> ..

1

::;> :;:; J, � s;

200.0 1 90.0 ISM

X : parts per Million : Be

i ' 170.0 160.0 150.0

I 140.0 ,13019 120.0 110.0 100.0 90.0 SO.O

i /\ /\ , 1 \

I.f) ClO 1' 0'\ ,., .... 0 0 to-- QO <1\ = '" 0\ '<> 0 M N N - .". "' ... '<> ¢\ oo t"'> t- ..,. <n - ,<> � � �«> � � � tt � ('f') N N """, ,..., _ ,oo.t

Spectrum 26 I 3C NMR ofMJS2097fr1 334

I I I 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 I

i j!\\ ; \ \

Ii'l .... r- '¢" t- \C � l;: tiH"'-l. C""i t'--C> "'& <:\ :t'--� "'1 2�� '" .,.. "" "M N N N

Co"'; ,"'1 i �.:j

- � �

o s�s�

r I I

I J I I I I i ( I I I j "'��------------------------------------�

.j , I • , I ' , I ' • I ' 10,0 9,0 S,O . . " ,7,0

Ii \\ Qf') � ('f'l. QO 'C ¢\ 'o::!" t.n QC lIl � "I!!" """ _ ¢o ec t-!.� r--! r..!

X : parts per Million : IH

r j�

) ! L

6,0 /\ I i

"' ''' .... r- "' .... �� "' ." ."

r I I

� , ':C'

5,� 1 ,\ , ,

"' .... '" ,,'''',,::, "' ''' ''' "'''' ''' .i) � �

, I i i . I

4,0 /\

Spectrum 27 IH NMR ofMJS2 1 19fr2346

I

( r I I ( I , I

3,0 .:[, :, . : /I /;! ; 1\\ / ! / " / !

r I

I ' I I ,

2,0 /\ I j • • I • 1,0 o

rJ2 "C ('t> r':> .... "'l = 9 N 00

w (1

� o foot) � C/J tv -...... \0 t:P tv w ..j::>. 0\

X 1 95.7055

II :l '" 't> !l1 is: == �' ... w (")

142.0044

138.1539 135.5257

128.5428 128.3824 128.0539 125.0284

1 16.991 2

77.5997 77.1260 76.6600

49.5688

40.9509

30.6981 29.9035 29.1472 28.1464

2 1 .5684

� o "'" .... '" � ... � --.l ., Q -"""

... '" �

th · o "'"

. .... .... g t;;

"'--., P -: .,-;/ ¢ ,/ /.- .... N <::> "'"

.... .... . g .... <:> 0 "'"

\Q g eo Q -

"'-. "'" / " -.l P , 0::>

'" g th g .... 'Q "'"

� w ." .... ,P :,;::. Q -4

" IV 0 "'"

? 0

0 -'

(Thousands)

o 1M W� �O 4M �o ao �� o �o ! " ' ! I J ' �-.1-'-L,..J ... l __ L¥lJ-..f.-J-W j j l t l l l ! l l ' I ! I I ! ' ! l t ! , ! ! l l " ' J..J..J..L I I ' I ! ! . ! • . • I " ! ' ! ' ! " ! ' ! ! I ! . " . ! . , ! ! , ! " , I , - e

� Cf) >=0

� -� � � � � l � �

1J). "0 � � -"'I = 9 N \0 ::c:

� o >-I-) � 1J). IV ....... ....... -.....l � ....... VI .......

\C!

� .. 't! .. a � ... is: I: §' 53

7.2454

5.8352

.... P Q

"" b "

<» b -

:-' Q

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5.8123 � -. ,� .. , ' ';

5.7738 /

5.0842 "-, 5.0623 "' ... �. 'Vt: 5.0229

// 'Q

�

i:��;� :?:>� 2.9231 2.6199 �=,

61 -._---. : i:��32 ��' 2.5366 ;/" 2.5101 1 2.3242 N 2.3077 : : :b 2.2747 _._._.c'_-: 1.8470 "7-" 1 .8205

__ 1 .7939 __ ._ : 1.5073 :/:;; : 1.4606 ;/ 1.4139 ./" 1.2417 b -0.8809 � , 0.8571 :...----0.8324

<::>

(Millions)

o to 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 1 1 .0 12.0 13.0 . r l l . j . ' . ! l l t l l ! . I · · , · , · · · · J '..L..J....L..1..U.J..1J....tJ..J-lJ..Jl...LJ.J....W....LJ I . I ( l l l t l ' • • ! " " " " . 1 " " " , • • 1 " 1 1 1 1 1 1 . 1 " • • • " • • 1 " " " " , 1 " " 1 1 1 • • 1 ' ! 1 1 1 1 1 1

�

�"

=, L==

1 (J) )=0

� ...., ::;> til ... 1. S;

E \

�-.--�-==--. c-==� _ _

-j

--l

X : pu1I ,.r MIIm : 13(;

... . ... . ,:.; '.-� -..... : .. ..

o s�s�

1.-.0 I 130.1 !lU ! 110.1 100.0 I ! � :. ; :':, :�, ' , ' 'S.," '-t . • :; ::.. ;;;: ; :: ..:: ....

.- ' .., ... ...

MJI 00.0 ;1' /i\ .Sf:! ��S 1=:""

Spectrum 30 l 3C NMR ofMJS2 1 17fr1 5 1 9

70.0 at !IU I .-.p ' � , 10.1 t I i l \ � I

I ... � �1U;��M��i � � !;it:: G;a " � �� :tt �

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