Acylsilanes and Their Applications in Organic ChemistryAmauri F. Patrocínio and Paulo J. S. Moran* Instituto de Química, Universidade Estadual de Campinas, CP 6154, 13083-970 Campinas

Review

Acylsilanes and Their Applications in Organic Chemistry

Amauri F. Patrocínio and Paulo J. S. Moran*

Instituto de Química, Universidade Estadual de Campinas, CP 6154, 13083-970 Campinas - SP, Brazil

Estudos sobre o emprego de acilsilanos em rotas sintéticas e as novas metodologias de preparaçãodesenvolvidas nos últimos anos, tornaram estes organo-silanos importantes reagentes para síntesede compostos orgânicos. Esta revisão apresenta algumas aplicações recentes e vários métodosdesenvolvidos para síntese de acilsilanos.

Current studies concerning the use of acylsilanes in a variety of organic synthetic routes and theimproved methodologies of their preparation have turned organosilanes into important reagents fororganic chemistry. This review discusses the recent employment of acylsilanes in organic synthesisand also effective methods for their preparation.

Keywords: organosilicon compounds, Brook rearrangement, carbonyl compounds, stereocontrol

J. Braz. Chem. Soc., Vol. 12, No. 1, 7-31, 2001.Printed in Brazil

c 2001 Soc. Bras. Química0103 - 5053 $6.00+0.00

Introduction

Acylsilanes (RCOSiR3) are compounds that have thesilicon directly attached to the carbonyl group, exhibitingunique chemical properties. The use of acylsilanes in organicsynthesis has increased significantly over the last few years dueto the discovery of valuable new reactions and the improvementof acylsilane synthesis methods. The substantial effect of theelectronic properties and the bulk of trimethylsilyl group maybe used to control the stereochemistry of reactions1. One of thewell-established uses of acylsilanes in organic synthesis is as analdehyde equivalent, in which a stereoselective nucleophilicattack on the carbonyl group, α to a chiral center, is followed bystereospecific replacement of the silyl group by hydrogen.Moreover, acylsilanes can be used as ester equivalents forchirality induction, since acylsilanes can be smoothly oxidizedto esters. The enantioselective reduction and the cyclizationreaction of acylsilanes appear to have substantial syntheticpotential. In the first part of this review we present some physicalproperties of acylsilanes as well as some classical reactionsinvolving organosilicon compounds. In the second part, wepresent some new work in this area as a complement to theprevious reviews2-7 and finally, in the third part, useful methodsof acylsilane synthesis.

Physical properties and classical reactions ofthe acylsilanes

In the organosilicon compounds class, the acylsilanes

are compounds that present particular physical and chemicalproperties. The spectral data of acylsilanes are well describedin the reviews by Brook2 and Page and co-workers3. Theinductive effect of the silicon favors the polarization of thecarbonyl group, which absorbs at a lower frequency thansimple ketones in the infrared and ultraviolet spectra. In 13CNMR spectroscopy, the signals for the carbonyl carbon arequite different from the corresponding ketones, appearing athigher δ values. The anisotropy effect and electronegativitydifferences also lead to higher δ values in the 1H NMR spectrafor hydrogens attached to the α-carbon of acylsilanes (exceptfor α,β-unsaturated). Table 1 shows some examples of IR andNMR spectral data for acylsilanes. Another interestingcharacteristic of acylsilanes is the abnormally long Si-CObond (1.926 Å), first observed by Trotter8 based on X-rayanalysis, which can be compared to the analogous bondlength in C-CO (1.51 Å)2 compounds. The same authorsdetermined that the carbonyl bond length is essentiallynormal, despite the low vibrational frequency.

Table 1. Infrared C=O absorption and NMR data of some acylsilanes2,3.

Acylsilane IR 13C NMR 1H NMRνC=O(cm-)a δ C=Oa δ CHCOa

MeCOSiMe3 1645 (1710) 247.6 (215) 2.20 (2.08)

PhCOSiMe3 1618 (1675) 233.6 (207) —

MeCOSiPh3 1645 240.1 2.30 (2.01)

PhCOSiPh3 1618 (1692) — —

t-BuCOSiMe3 1636 249.0 (215) —

Me3SiCOSiMe3 1570 318.2 —

PhCH2COSiMe3 1635 — 3.77 (3.55)

CH2=CHCOSiMe3 1641 237.0 6.28 (6.88)aValues in parenthesis are for analogues in which the silicon atom hasbeen replaced by carbon.e-mail: [email protected]

8 Patrocínio & Moran J. Braz. Chem. Soc.

Studies have shown that acylsilanes in general behaveas ordinary ketones. However, in some cases, thesecompounds have abnormal chemical behavior. Due to theintrinsic properties already mentioned, these compoundsshould undergo many unusual reactions. For example, inreactions of aroylsilanes with nucleophiles, the Brookrearrangement9 is very common. An example is the knownhydrolysis of aroylsilanes 1 to the corresponding aldehydes5, promoted by traces of OH- (Scheme 1).

The Brook rearrangement, after carbonyl addition of anucleophilic reagent, is commonly observed in aroylsilanesdue to the relative stabilization of the carbanionintermediate 3 by the aromatic ring. Two classicalexamples in this context are presented in Scheme 2, wherethe silyloxyalkene 6 is formed only when an anion-stabilizing group is attached to the carbonyl group2.

Brook investigated the great reactivity of acylsilanes

Brookre a rrangm ent

ArCHO

R3SiOHOH- H2OR3Si

O

ArOHR3Si

O

Ar

1 2 3 4 5

R3SiO C

Ar

OH

R3SiO C

Ar

OH

H

Scheme 1.

R3Si Ar

OCH2N2 C

O

R3Si

CH2

Ar

N2

C

R3SiO

H2C Ar

1

CH2 PPh3 C

O

R3Si

CH2

Ar

PPh3

6

-N2

-PPh3

Scheme 2.

pathway b

pathway a

ROSiPh3H

O

PhRO-

H C

OSiPh3

OR

Ph

Brookrearrangement

Ph3Si C

O

OR

Ph

H

O

PhSi

Ph

Ph

Ph

ORcleavage

O

PhSiPh

Ph

PhROO

PhSiPh

Ph

Ph

RO-ROH

RO-

ROH

78

8

Scheme 3.

towards nucleophilic addition9,10. His work is historicallyimportant because it led to a better knowledge of the reactionpathway. A nucleophilic attack of alkoxide ion on the siliconatom of acylsilane 7 was initially proposed for the formationof aldehyde 8 (Scheme 3, pathway a). Later, Brook proposedanother competitive pathway, which involves a nucleophilicattack by the alkoxide ion at the carbonyl group of 7(Scheme 3, pathway b). Using the optically active acylsilane(-)-9 in reactions with different alkoxide ions, 10 was reducedby LiAlH 4 to give (-)-11 (Scheme 4). Although the opticalpurities of (-)-11 were observed to be dependent on the bulkof the alkoxide ion (EtO- 22% vs. t-BuO- 65%), in allreactions with chiral acylsilane (-)-9 the enantiomer (-)-11was predominant, showing the retention of configuration atsilicon. Therefore the bulkier alkoxides find it more difficultto attack at silicon and, consequently, the attack at thecarbonyl group becomes relatively easier11.

Vol. 12 No. 1, 2001 Acylsilanes and Their Applications in Organic Chemistry 9

Schemes 5 and 6 show recent examples of acylsilanereactions involving the Brook rearrangement. Theacylsilane 12 reacts with amines to form the imine 13 oraminals 1412. The acylsilane 15 reacts with cyanide anionunder liquid-liquid (CH2Cl2-H2O) phase-transfer catalyticconditions to form O-silylated cyanohydrin 1713.

Novel work involving acylsilane chemistry

Herein some of the most important syntheticapplications of acylsilanes will be presented, focusingespecially on reports of the last ten years.

a. Stereocontrolled nucleophilic additions

The first study involving enantioselective addition toacylsilanes was reported by Mosher14 in which he used an

OSi Np

Ph

Me

ORMeMe

O

SiNp

Ph

MeMe

OH

Me

PhNpSi

OR

LiAlH 4 Si Np

Ph

MeH

(-)-1110(-)-9

Np: Naphthyl

R O /R OH

Scheme 4.

"dark"

"dark"12

13

14

N

H

Ph3Si C

O

N

PhH

Ph3Si

O

PhH2NCH2CH(CH3)2

Ph3Si C

O

NH2CH2CH(CH3)2

Ph Ph3SiO C

H

NHCH2CH(CH3)2

Ph

PhCH NCH2CH(CH3)2 Ph3SiOH

Ph3SiO C

H

N

PhNH

N C

H

N

Ph Ph3SiOH

Scheme 5.

t-BuMe2Si

O

R

KCN

PTCCH2Cl2-H2O (1:1)

t-BuMe2Si

R

O

CN

B rookre a rra nge m e nt

15 16 17 (7 4 -9 6 %

R = Me, CH2CH2OMe, Ph,

PTC: n-Bu4PBr (20 mol%)

R'

t-BuMe2SiO

R CN

Scheme 6.

optically active Grignard reagent to reduce benzoyl-triphenylsilane and benzoyltrimethylsilane in lowenantiomeric excess. Due to the relative facility that the silylmoiety can be removed and replaced by hydrogen, generallyby the action of fluoride ion, acylsilanes can be considered asaldehyde equivalents in nucleophilic additions. Addition ofnucleophiles can occur with a high Cram selectivity whenthe chiral center in the acylsilane is on the α-carbon, as in 18(Scheme 7), and even in some cases where the chiral center ison the β-carbon1, as in 19 (Scheme 8).

In general, the protiodesilylation (replacement of theR3Si moiety by H) occurs with a high level ofstereoselectivity through the Brook rearrangement15. Tworecent examples are shown in the Schemes 8 and 9 in whichhigh stereocontrol was obtained in asymmetric inductionin the syntheses of calcitriol lactone derivatives 2016 andβ-aminoalcohols 21 and 2217. Scheme 10 illustrates a key


step of Corey’s total synthesis of pentacyclic triterpene 24of the β-Amyrin family18. The addition of 2-propenyl-lithium to acylsilane 23, followed by a Brook

HOH

Me

H

Me

Me

24

1.

(82%) O

O

SiMe2Ph

Li

O

OSiMe2Ph

BrBrBr

,

23

S h 10

3.

Et2O, -78 oC, 1h

2. BaI2, THF, -78 oC, 1h

, -78 to 0 oC,15 min

Scheme 10.

Ph

Me

SiMe3

O

Ph

Me

Bu

SiMe3HOPh

Me

Bu

HHO

TBAF

(99:1)18

BuLi

Scheme 7.

Tiiv

19 syn-20 (93-95% d.e., 52-96% yield

OBn

Nu

HOHTBAF

OBn

OHSiMe3

Nu

Nu-M

SiMe3

OBn

O

CH2 Cl2

Nu-M = Allyl-S iMe 3 , Me tha llyl-S iMe3

(93-95% d.e., 90% yield)

Scheme 8.

NHBoc

SiMe2Ph

OAllyl brom ide /In

THF/1 5 h/rt

21 (9 2 %)

TB AF

NHBoc

SiMe2PhHO

NHBoc

HO H

(9 8 % d.e ., 9 6 % yie ld)

OSiMe2t-Bu

OEt

NHBoc

SiMe2PhHOO

OEtTB AF

NHBoc

HO H O

OEt

(9 8 % d.e ., 6 7 % yie ld) 22 (9 8 % d.e ., 6 7 % yie ld)

B F3 E t2 O, CH2 Cl2-7 8 o C, 4 8 h

Scheme 9.

rearrangement and coupling with allylic bromide, resultedin the Z-olefin in an overall yield of 82% with excellentstereoselectivity (> 95%).

d)


Syn-α-alkoxy-(β-silyloxy)acylsilanes 25 undergochelation-controlled addition reactions with vinyl andphenyl Grignard reagents affording all-syn triols 26 withdiastereoselectivities up to >98:2 (Scheme 11)19,20.

The allylation reaction of acylsilane 27 has beenapplied to a stereoselective synthesis of allyl myrtanols29 and 31 (Scheme 12)21. In this case, the reaction of 27with tetraallyltin/Sc(OTf)3 provides an asymmetricinduction opposite to that observed by usingallyltrimethylsilane/TiCl4. The configurations of 28 and30 were tentatively assigned taking into account that theprotiodesilylation generally proceeds with complete

retention of configuration15,22. The B-allyl(diisopino-campheyl)-borane has been also used for asymmetricallylation of acylsilanes 32 (Scheme 13)23.

The addition of alkyl and phenyl lithium24,25 or Grignardreagents (Scheme 14)26 to acylsilanes 33 having a chiralcenter at silicon is also diastereoselective. High diastereo-selective excesses are obtained with Grignard reagents bymeans of a chelate-controlled reaction pathway involvingintermediate 34 (Scheme 15)24. Cyclopropanediol monosilylethers 36 and 37 are obtained with good diastereoselectivityfrom reaction of benzoylsilane 35 with lithium enolatesderived from methylketones (Scheme 16)27.

R3Si

O OTBS

ORNu-M R3Si

OTBSOH

Nu

OR

25

Nu-M: Allyl-Sn(Bu)3/ZnCl2; Vinyl-MgBr; Ph-MgBrR = MOM; BOM

26 (48-96% d.e.; 86-96% yield

Scheme 11.

28 (69% d.e.; 53% yield)

30 (80% d.e.; 51% yield)

SiMe2PhO

H

(CH2=CHCH2)4Sn Sc(OTf)3CH2Cl2, 10 oC

CH2=CHCH2SiMe3

TiCl4

CH2Cl2, -70 oC

OHPhMe2Si

H

HOPhMe2Si

H

TBAF

THF, r.t.

THF, r.t.

TBAF

OHH

H

HOH

H

29

31

27

Scheme 12.

R1

O

SiR2R

32

(+)-[Ipc]2BAllyl

R1

HO SiR2R

32

(0 2 -9 2 % e .e .

(+)-[Ipc]2B Allyl: (+)-B -a llyldiis opinoca m phe ylbora ne

32

R1 = 4-CF3-C6H4, 4-Me-C6H4, cyclopentyl

R2, R3 = Me, Et, Ph

Scheme 13.

d)

)


Ethynyl triphenylsilyl ketone 38 undergo stereospecificMichael addition with silylated nucleophiles28, dialkyl-cuprates29 and tributylstannyl-cuprate30 to afford only onedouble bond isomer of β-functionalized propenoylsilanesdepending on the type of nucleophile used. An interestingapplication of these reactions is the preparation of a varietyof α,β-unsaturated acylsilanes 40 by reaction of 38 withtrimethylsilyl iodide yielding 39, which undergoesstereospecific palladium-catalyzed coupling with tincompounds (Scheme 17)31.

b. Stereocontrolled aldol reactions

Lithium enolates of propanoyl silanes 41 react witharyl and alkyl aldehydes to afford mainly syn-β-hydroxyacylsilanes 42, which can be converted into 43 asthe major product (Scheme 18) in 31-68% overall yields32.While benzaldehyde gives a modest syn/anti ratio,isobutyraldehyde gives good diastereoselectivity (syn/anti> 20). Adehydes having a chiral center on the α-carbonreact with 41, giving 44 in good diastereoselectivity.

O

SiPh3

Me3 S iI

I

O

SiPh3

RSnBu3, PdCl2(MeCN)2

R

O

SiPh3

38 39 40 (6 4 -8 6 %)

R = Me3 S iC C, CH2 =C(OE t), CH2 CH, 2 -furyl, BOCNHCH2 CH=CH, P h3 S iCOCH=CH

Me3 S iNuNu

HH

SiPh3O

Nu = H2 N, Me NH, S P h

(9-79% d.e.; 63-98% yield

R2

HO R3

Si

R1

Me

Ph

NH4Cl sat.R2 Si

OR1

Me

Ph33

-80 oC-80 oC

R3MgX/Et2O

R1 = n-Bu, t-Bu, α−Np; R2 = Me, Ph; R3 = Me, Ph

Scheme 14.

t-BuSi

Me

OR1R2

O

t-Bu

Si

Me

O

R1R2

R3

OH

t-BuSi

Me

OR1R2

O

MgBr

R3

( 46 -99 % d.e .; 4 2 -98 % yie l

E t2 O or T HF

34R1 = Me OCH2 CH2 , P hCH2 ; R

2 = Me , P h; R

3 = Me , B u, P h

R3 MgB r

Scheme 15.

Ph

O

SiMe3

OLi

R

THF

OHMe3SiO

RPh

OSiMe3HO

RPh

(64-75%) (7-21%)

R = Et, n-Pr, i-Pr, t-Bu

Ph

Me3Si O O

R Ph

O

R

Me3SiO

Ph R

Me3SiO O

35

36 37

-80 to -30 oC

Scheme 16.

Scheme 17.

d)

d)

R = Me3SiC≡C


Stereoselective intramolecular aldol reaction wasperformed with bis-acylsilanes under Lewis acid activationto give cis-β-hydroxyacylsilanes33.

c. Acylsilanes in radical reactions

Lanthanoids, especially ytterbium and samarium,promote several kinds of reactions with alkanoyl andaroylsilanes. The mechanism of these reactions is alwaysdependent on the metal and on the group attached to thecarbonyl group (Scheme 19). An interesting point is the

production of acetylene derivatives 46, which are probablyformed by the addition of a silyl-radical 45 to anotheracylsilane molecule and involve two consecutive Brookrearrangements34. Other reactions such as intramolecularradical cyclization reactions of acylsilanes (Scheme 20),aldol reactions (Scheme 21) and pinacol couplings(Scheme 22) take place mediated by SmI2

35. The examplepresented in Scheme 20 shows an interesting cis-stereoselectivity observed for the cyclization of theacyltrimethylsilyl group (giving 47), while the diphenyl-methylsilyl group gave poor (48:49) stereoselectivity.

41 42 43

O

SiR13 R

2

OH O

OSiR13 R

2

OH O

OH

3. H2O2

(60 to >90% d.e.; 31-68% yiel

R3

OH

SiR31

O44 (72 to >90% d.e.; 44-48% yield)

1. LDA -78 oC2. R2CHO

1. LDA, -78 oC

2. R3 CHO

R1 = Et or R13 = t-BuMe2; R

2 = Ph, i-Pr; R3 = Ph, (CH3)2C=CH

R = a ryl a nd Ln = S m I2

R = a lkyl a nd Ln = S m I2

R

O

SiMe3

R

O

SiMe3

R C

OLn

SiMe3

R CH

OH

SiMe3

R = a ryl

Ln = Y bR C

SiMe3

OYbLn

THF C CO O

Yb

R SiMe3

Me3Si R

C C

SiMe3

R

Me3SiOYbO

R

C C RRYb(OSiMe3)246

45

O

SiMeR2

SiMe3

OH

SiMePh2

OH

OH

SiMePh2

R = Ph

R = Me

SmI2/HMPA/t-BuOH

48 49

47 (26%)

(49/48: 70/30 to 40/60; 32% yield)

Scheme 18.

Scheme 20.

Scheme 19.

d)

R = alkyl, arylLn = SmI2


Trialkyltin radicals can promote intramolecular cyclizationof acylsilanes 53-55 with alkyl, aryl and vinyl radicals, affordingcyclopentyl silyl ethers 56 and 57 and enol silyl ether 58(Scheme 23)36 by a mechanism involving a radical Brookrearrangement, as shown in the example outlined in the Scheme2436c. An interesting application of the tandem cyclization-addition reaction of acylsilanes is the diastereoselective

synthesis of endo bicyclic alcohol 60 from acylsilane 59(Scheme 25)36a. On the other hand, bicyclic spiro-lactones 62and 63 are obtained in the reaction of 61 with methyl acrylateand tributyltin hydride or CH2=C(CO2Et)CH2SnBu3 (Scheme26)37. For other examples see Tsai38, including tandemcyclizations with acylsilanes containing C=C or CºC groupsattached at the silicon atom.

O

SiMe3

O SmI2

THF, 22 oC

O

OH

SiMe351 (56 %)50

SmI2

HMPA

O

SiMe3

OSm

SiMe3

52 (30%)

O

SiMe3

O

Br O

SiMe2Ph

Me3Si

O

Br

OSiMe3

56 (6 0 %)

Bu3SnH/benzene

AIBN, reflux

Bu3SnH/benzene

OSiMe2Ph

57 (8 3 %)

Ph2MeSi

OBr Bu3SnH/benzene

OSiMePh2

58 (6 2 %)

53

54

55

AIB N, 8 0 o C, hv

8 0 o C, 2 h

O

SiMe3

CH2

OSiMe3

Bu3SnH

AIBN

SiMe3O

53

OSiMe3H

56

Scheme 21.

Scheme 22.

Scheme 23.

Scheme 24.

SiMe3

O

Br

1. n-Bu3SnH, AIBN2. TBAF

OH

H

Me

60 (81%)59Scheme 25.


d. Cyclization reactions of acylsilanes

In addition to the examples cited above, many othercyclization reactions involving acylsilanes can be foundin the literature. Carbonyl acylsilanes 64 provide furans65 under milder conditions and in higher yields than thecommon cyclization reactions of dicarbonyl compounds.This advantage is derived from the high nucleophilicityof the carbonylic oxygen in acylsilanes, due to the

contribution of the polarized resonance form II (Scheme27)39. Scheme 28 presents examples of syntheses ofdisilylhydropyranes 68 and disilylfurans 69 through asimilar cyclization of 1,5-bis-acylsilanes 6640 and 1,4-bis-acylsilanes 6741 respectively, catalyzed by p-toluene-sulfonic acid (TsOH). The nucleophilicity of the carbonylicoxygen in acylsilane is also observed in the cyclization ofγ- and δ-haloacylsilanes 70 affording 71 in reasonable togood yield (Scheme 29)42.

SiMe3

O

I61

1. CH2=CHCO2Me, Bu3SnH, AIBN2. TBAF

1. CH2=C(CO2Et)CH2SnBu3, AIBN2. TBAF

O O

O O

62 (6 4 %)

63 (3 9 %)

R1 = H, Me; R2 = H, Me; R3 = H, Me, Ph

Ph2MeSi

O

R3

R2

R1

OPh2MeSi

O

R3

R2

R1

O O

R3 R2

Ph2MeSiR1

OH

O

R3 R2

Ph2MeSi R1

I II64

65 (57-87%)

H+

-H3O+

R12R

2Si

O

R3SiR4

2R5

OTsOH

O

R

SiR42R

5R2R2Si

66 68 (50 - 94%)

3

1

R12R

2Si

O

O

SiR32R

4

67

TsOHO SiR3

2R4R1

2R2Si

69 (68-71%)

∆

∆

R1 = R2 = R3 = R4 = MeR1 = R3 = Me; R2 = R4 = t-Bu

R1 = P h or Me ; R2 = Me ; n =1 or 2

O

R12R

2Si

X

n

NMP

n

NMP : N-m e thylpyrrol idone

X

-HX

nR12R

2Si

O

71 (4 9 - 9 7 %70R1

2R2Si

O

Scheme 26.

Scheme 27.

Scheme 28.

Scheme 29.

)


α,β-Unsaturated acylsilanes 72 combine withallenylsilanes 73 in presence of TiCl4 to produce [3+2] or[3+3] annulation products 74 and 75 in good yield. The courseof the annulation reactions can be controlled to produce eitherfive- or six-membered rings by controlling the reactiontemperature or by using an appropriate trialkylsilyl group in72 (Scheme 30)43, since the initially produced cyclopenteneundergoes rearrangement at higher temperatures.

On the other hand, α,β-unsaturated acylsilanes 76 andlithium enolates of α,β-unsaturated methyl ketones 77 affordinteresting [3+4]-annulation products 78 (Scheme 31)44.These stereospecific reactions were proposed to occur by aconcerted anionic oxy-Cope rearrangement throughcyclopropanediolate intermediate 80. The addition of cyanide

anion13,45 to acylsilane 81 (or phenyllithium in an analogousreaction)46 produces a cyanohydrin which undergoes aBrook rearrangement, followed by an intramolecularalkylation to give cyclopropane 82 (Scheme 32).

e. Thioacylsilanes: preparation and synthetic applications

The replacement of the C=O with the C=S functionalityin acylsilanes is possible by reacting acylsilanes such as83 with H2S/HCl or by treatment with (Me3Si)2S underCoCl2 catalysis47. These highly reactive compounds areemployed as unstable thioaldehyde equivalents and alsoto afford molecules containing the Si-C-S unit or to preparesulfur heterocycles. Contrary to the thiocarbonylanalogues, the thioacylsilanes as 84 having an α-hydrogen

72 73

74 (78%)

75 (56%)

SiMe3

R = t-Bu

R = Me

t-BuMe2Si

O

SiMe3

O

SiMe3

SiMe2R

O

TiCl4/CH2Cl2

-78 oC, 1h

-50 oC, 2h

O

TBS

X

OLi

R2

R1

O

TBSO

R1

R2

X

OR1

R2

O

1 .NB S

2 .TB AFor m CP B A

TBS: t-BuMe2SiTBAF: tetra-n-butylammonium fluoridemCPBA: m-chloroperbenzoic acid

mechanism:

O

SiMe2But

XOLi

R

LiO

X

SiMe2But

OR

Brook rearrangement

OSiMe2But

X OLiR

oxy-Cope rearrangement

OLiR

X

OSiMe2But

Li

(67-84%, X = TMS)(26-72%, X = SnBu3)

(75-89%, from 78 X = TMS)(57-89%, from 78 X = SnBu

76 77 78 79

80

OSiMe2But

X OR

Scheme 30.

Scheme 31.

))

mechanism:


bonded to the C=S group exist in the thioenol tautomericform affording compounds Z-α-silyl vinyl mercaptans48,such as 85. These are interesting molecules because twofunctional groups with opposite polarization are bondedto a single double bond. An example of these reactions isconcisely outlined in Scheme 33 where halothioacylsilanes84 are cyclized in the presence of a base to provide 2-silyl-thiocycloalkyl-2-enes 86 in good yields49. Thesecompounds react with acid chlorides, such as 88 and 90,in presence of a Lewis acid to give interesting bicyclic 89

or tricyclic 91 structures depending upon the nature of thealkyl chloride (Scheme 34)50. Scheme 35 presents somereactions of thioacylsilanes 92 containing the ferrocenemoiety attached to the thiocarbonyl group51. Unlikeketones and common acylsilanes, which need long reactionperiods and high temperatures for replacement of the C=Owith the C=S functionality, acylsilanes containingferrocene are converted readily into thioacylsilanes byLawesson’s52 reagent in high yields in a few minutes atroom temperature.

t-BuMe2Si

O

Br

KCN (1 .1 e q)

1 8 -crown-6CH2 Cl2

t-BuMe2Si O

Br

CN

t-BuMe2SiO

Br

CN

OSiMe2t-Bu

CN

(7 5 %)

81

82S 32

85

84

n = 2-5, 9, 11; X = Cl, Br

NaOH

NaOHSPhMe2Si R

NaHCO3

Et2O

H2S/HCl

(63-100%)86

83

SiMe2Ph

X

O

SiMe2Ph

X

S

SiMe2Ph

X

SH

(87-100%)

( )n

( )n ( )n

( )n

n Cl

O

AgBF4

CH2Cl2, (ClCH2)2

Cl

O

AgBF4

CH2Cl2

S

O

H

H

n = 3

(n = 2-5, 83-91%

(45%)

87 88 89

90

91

S SiMe3 nS

O

Scheme 32.

Scheme 33.

Scheme 34.

%)


f. Acylsilanes derived from natural products

We have already described the application of acylsilanesfor the synthesis of a pentacyclic triterpene, vitamin D3metabolites and in aminoalcohol synthesis. However, the useof acylsilane moiety in natural product synthesis is still veryrestricted and few examples are found in the literature. Scheme36 shows an “acylsilane-sugar” 93 as the starting material toprepare C-difluorosaccharide 94. Sugar chemistry may be agood option for the preparation of optically active silanes,little explored to date53. The proposed mechanism of thiscondensation of the saccharides is based on the highly reactive

La we s s on`sre a ge nt

PPh3

C6H6, ∆

Fc SiMe2R3

S R1R

2CN2

Et2O

SFc

R3Me2Si

R1

R2

C CFc

R3Me2Si

R1

R2

C CR

1

R2

Fc

H

( 59 - 8 4 % )

( 8 9 - 9 0 %)

S

SiMe2R3

Fc

( 80 - 8 2 % )

S

SiMe2R3

FcT B A F S

HFc

( 84 - 9 7 % )

( 55 - 9 4 % )9 2

(93% when R3 = Me)

R1 = H or Ph; R2 = CO2Et or Ph; R3 = Me or Ph; Fc = ferrocenyl

T BAF

T HF, r.t .

Fc SiMe2R3

O

difluorosilyl enol ether 95, formed by the reaction of acylsilanewith trifluoromethylsilane, followed by Brook rearrangementand the subsequent loss of fluoride ion, as outlined in Scheme3754. The reaction of acylsilanes with trifluoromethyl-trimethylsilane has been utilized to afford alicyclic 2-fluoro-1,3-diketone55, 2,2-difluoro-1,5-diketone56 and “difluoro-ar-tumerone” 9757, a sesquiterpene derivative with antitumoractivity, as shown in Scheme 38. The stereoselective synthesisof β- and γ-amino alcohols 100 and 101, starting from a naturalaminoacid and proceeding through the homochiralaminoacylsilanes 98 and 99, reveals the great potential of thesecompounds as chiral building blocks (Scheme 39)58.

OOB n

OO

OOAc

AcOO

F F

94 (α/β: 8 0 /2 0 ; 7 5 % yie ld)93

OOAc

AcOAcO

Me3Si

O

OOB n

OO

1. CF3SiMe3/CH2Cl2/cat./O oC

2 .

cat.: Bu4N+ Ph3SnF2

-

/BF3Et2O/CH2Cl2-4 0 o C

93

94

mechanism:

CH2Cl2/cat.

Me3Si

O

R

CF3SiMe3 Me3SiO

RF3C

Brookrearrangement

OSiMe3

RF2C

F

-F-

OOAc

AcOAcO OSiMe3

RF

FOOAc

AcOO

F FR

cat. Bu4N+ Ph3SnF2

-

95

O

OO

OBn

R =

BF3Et2O

Scheme 35.

Scheme 36.

Scheme 37.


g. Reactions of α-haloacylsilanes

In spite of α-haloacylsilanes being little known, theirreactions are very interesting due to a variety of productsthat they provide. Ketone enolates usually react withα-chloroacyltrimethylsilane under mild reaction conditionsto give the corresponding 1,3-dicarbonyl compounds59.Titanium tetrachloride promotes coupling reactions of α-chloroacylsilanes 102 to afford α-silyl ketones 103, β,γ-unsaturated ketones 106 and Friedel-Crafts type products104 and 105 (Scheme 40). The intermediate acyl cationequivalent 109 was proposed to be responsible for theformation of 103 (Scheme 41). An interesting observationin these reactions is the migration of silyl group andsubsequent loss of this moiety, which happens when R’ =Me or Ph, but not t-butyl. Apparently, the formation of theintermediate silyl enol ether 107 is difficult when the silylgroup is very bulky (R’ = t-Bu). The presence of intermediate107 was inferred from the aldol type products 10860 isolatedupon addition of acetaldehyde to the reaction mixture.Another example involving these α-haloacylsilanes ispresented in Scheme 42, where α-bromoacylsilane 110reacts with zinc in a Reformatsky type reaction giving 111with high diastereoselectivity61. The addition of

triethylborane to α-iodoacylsilane provides boron enolatethat reacts with aldehydes to give aldol types adducts withgood diastereoselectivity in reasonable yields61.

h. Acylsilane oxidation

The acylsilanes have a much smaller oxidationpotential than aldehydes and ketones due to the largeinteraction of the C-Si bond with the lone electron pair ofthe carbonyl oxygen62. This characteristic allows theacylsilanes to suffer oxidation to the correspondingcarboxylic acids mediated by peroxides63, ozone64 andelectrochemistry65. The oxidation of acylsilanes has beenshowing of great importance in organic synthesis, forexample in chain homologation66 and as a precursor forchiral esters (Scheme 43)67. The most common method foroxidation of acylsilanes utilizes peroxides but theelectrochemical method, although seldom applied, appearsto be advantageous because it permits the direct preparationof acids, esters or nitrogen derivatives, depending upon theadditive present during electrolysis. Recently, we introduceda new method for direct esterification of alkyl andaroylsilanes by means of iron (III) ion or nitric acid oxidationin dilute alcohol solution (Scheme 44)68.

, ZnBr2

cat.: Bu4N+ Ph3SnF2

-

O

SiMe3 2. Br O

F

F

97 (53%)

96

1. CF3SiMe3/CH2Cl2/cat.

PhNPht

Cl

O

(P hMe2 S i)2 Cu(CN)(ZnCl)2 PhNPht

SiMe2Ph

O

Me3Si

PhNPht

SiMe2PhHO

TBAF, T HF

r.t .Ph

NPht

HO

9 8 ( 65 % )

(>98% d.e., 75% yield)100 (>98%d.e., 60% yield)Ph

NPht

SiMe2Ph

O

Me3Si

TiCl 4 , CH2 Cl2 ,Ph

NPht

SiMe2Ph

OHPh

NPhtOHTB AF , THF

r.t .

(>98% d.e., 80% yield) 101 (>98% d.e., 72% yield)

99

THF, -20 o C TiCl 4 , CH2 Cl2 ,

-78 o C

-78 o C

Scheme 38.

Scheme 39.


work-up

O

Cl

RSiMe2R'

TiCl4, CH2Cl2 TiCl4, CH2Cl2

O

R

t-BuMe2Si

O

R

O

R

OMe

H (OMe)

t-BuMe2Si

RO

OMe

H (OMe)

102103 (7 8 %)

106 (7 6 -9 8 %)

104 (7 7 -8 4 %)

105 (6 6 -8 7 %)TiCl4, CH2Cl2

OSiMe2R'

R

O

R

HCH3

OH

108 (7 0 %)107

R ' = Me ,P h

R ' = t-B u

H (OMe)

OMeSiMe3

SiMe3

CH3 CHO

R' = Me

R' = t-B u

R = n-C3 H7 , n-C6 H1 3

R' = t-Bu

mechanism: SiMe3

O

SiMe2t-Bu

R

Cl4TiO

SiMe2t-BuCl

R

103

109

102TiCl4

Br

R

SiMe3

OZn

R

SiMe3

OZnBrPhCHO

R

SiMe3

O

Ph

BrZnO

PhCHO

R

SiMe3

OO

Ph

C

OZnBr

Ph

H

R

SiMe3

OZnBrO

Ph

C

O

Ph

RSiMe3

OBrZnO

Ph

O

PhH

RSiMe3

O

Ph

O

PhOH

110

111 (single diastereomer; 80% yield)

R = n-C6H13

E t2 Zn/CH2 I2

2. H2O2, NaOH

CH3 N2

Me3Si

OHC4H9 HO

OC4H9 MeO

OC4H9

1 . [O]-S we rnC4H9Me3Si

OH

(9 7%) (84 %) (86 %)

Scheme 40.

Scheme 41.

Scheme 43.

Scheme 42.


In this context, an important property of the acylsilanesis their oxidation through photoprocesses, affordingcompounds such as carboxylic acids (promoted by roomlight)69,70 or silylesters 112 and viniloxysilanes 114 asprincipal products (Scheme 45)71. Also see Brook72 for otherexamples of classical photolyses reactions of acylsilanes.

i. Enantioselective reduction of acylsilanes

Chiral boranes have been used for enantioselectivereduction of acylsilanes affording optically active alcohols(Scheme 46)73,74. Compound 115 was used as homochiralbuilding block in the synthesis of (+)-sesbanimide A20.Scheme 47 shows an interesting reduction of α,β-unsaturated acylsilanes 116, which is mediated by thechiral lithium amide 117 affording alcohols 118 inexcellent enantiomeric excesses75.

Because of the higher reactivity of the carbonyl groupof acylsilanes compared to the analogous ketones,attributed mainly to the high polarization of theacylsilane carbonyl group, these compounds can reactwith weak nucleophiles. Therefore, these organosilanes

are important substrates for bioreductions, from whichthe corresponding α-hydroxysilanes can be obtained withhigh enantiomeric excesses by using a variety of isolatedenzymes or microorganisms76. Scheme 48 shows one ofthe first reports of this methodology, the acylsilane 119being reduced by Trigonopsis variabilis 20 times fasterthan the analogue dimethylphenylpropanone77. AlthoughSaccharomyces cerevisiae is one of the most commonlyused micro-organisms in enantioselective reductions ofketones, it is usually inert toward substrates possessingsteric hindrance78 or having electron-donating groupsattached to the aromatic ring of the aroyl ketone79. Onthe other hand, aroylsilanes such as 121 were reduced bythis microorganism, affording the corresponding α-hydroxy-silanes 120 and 122 with enantiomeric excessesvarying from 43 to 88%, Scheme 4980. The disadvantagein using acylsilane bioreductions is the required lengthyperiod of reaction, which generally leads to the formationof by-products such as primary alcohols and carboxylicacids from C-Si bond cleavage. A radical oxidation ofacylsilanes seems to be responsible for the formation ofcarboxylic acids81.

r.t.R SiMe3

OHNO3

R SiMe3

O

R OR'

O

R'OSiMe3R'OH

(88-100%)

R = Ph, p-MeOC6H4, C5H11; R`OH = H2O, MeOH, EtOH, n-PrOH, n-BuOH, n-C6H13OH

CH3 SiMe3

Oλ > 345 nm

O2 CH3 OSiMe3

O

λ > 280 nmAr, 10 K

Me3Si O CH3

Me3Si O CH2

Me3Si O

CH3

Me3Si O CH3

Me3Si O

CH2

112

s-E-113 s-Z-113

Ar, 45 K

s-E-114 s-Z-114

Scheme 44.

Scheme 45.


THF

O

SiMe2R3

R1

R2

N

NN Bu

t

Li

Ph H

SiMe2R3

R1

R2

HO H

(ee > 99%; 31 - 68% yiel

3 0 m in,

R1 = Me, i-Pr, -(CH2)3-; R2 = H; R3 = t-Bu or Ph

116

117

118

Si

Me

Ph

Me

C

O

Me

Trigonopsis variabilisSi

Me

Ph

Me

C

OH

Me

H

119 (86% e.e.; 70% yield

121 S-(-)-122R-(+)-120

S .cS .cSiMe3

OHH

GG

OH

SiMe3

H

G

O

SiMe3

(79% e.e.; 20% yield) (43-88% e.e.; 45-70% yield)

S.c. = Saccharomyces cerevisiae

G = H; 4-MeO; 3,4-(OMe)2; 3,4-(OCH2G = 2-MeO

Scheme 46.

Scheme 47.

Scheme 48.

Scheme 49.

In Scheme 50 there is an interesting example of thebioreduction of a racemic acylsilane (±)-123 containingasymmetric silicon that was applied to afford chiral silylcompounds. Thus, acylsilane (-)-123, prepared byoxidation of (+)-124, was treated with phenyllithium, theasymmetric silyl group being a chiral inductor. After theBrook rearrangement promoted by KH, the silyl group wasremoved by tetrabutylammonium fluoride (TBAF), givingthe enantiomerically enriched alcohol (R)-(+)-12725.

Chiral secondary silyl alcohols may also suffer thermalrearrangements through their acylated derivatives followedby oxidative cleavage74,82 that occurs with highstereocontrol83, giving optically active alcohols.

Synthesis of acylsilanes

In 1957, Brook reported the first synthesis of an acylsilane,benzoyltriphenylsilane, which was accomplished by the

R' = Me, Et, n-Bu, i-Pr, t-Bu, Ph ; R = Me ; Et ; i-Pr, H2C=CH, (CH3)2C=CH,

R

OH

SiR'3

H

R SiR'3

O

(8 0 -9 8 % e .e .; 11 -93 % yie ld)

Me2PhSiOBn

O

(-)-[Ipc]2BCl

(R)-(+)-115 (87-92% e.e.; 76% yield

a )

b)

(-)-[Ipc]2BCl

(-)-[Ipc]2BCl: (-)-B-chlorodiisopinocampheylborane

,

Me2PhSiOBn

OHH

,

M e

O,

d)

d)

d)

)


reaction of triphenylsilylpotassium with benzoyl chloridein only 6% yield. The same compound was prepared inmuch better yield by hydrolysis of dihalide compound128 (Scheme 51)84.

The biggest problem in the synthesis of acylsilanes isthe instability of these compounds under many reaction

conditions which may lead to C-Si bond cleavage. In thisreview, some of the methodologies developed foracylsilanes synthesis will be introduced concisely. A usefulsummary is presented in the Chart, showing that some ofthe common organic functional groups may be used forthe preparation of acylsilanes.

Si

BnO

Me

O

Met-Bu Si

BnO

Me

OH

MeHt-Bu Si

BnO

t-BuMe

OH

MeH

Trigonopsis variabilis

Si

BnO

t-BuMe

O

Me

PhLi

Si

BnO

t-BuMe

OH

PhMe

(+)-124 (96% e.e.)( )-123

KH

( )-123 (95%)

(+)-125 (96%e.e.)

(COCl)2, Et3N,DMSO

126 (86%)

Si

BnO

t-BuMe

O H

PhMe

TBAF HO H

PhMe

(R)-(+)-127 (88%e.e; 70% yiel

Si

Ph

Ph

Ph

CH2Ph 2 NBS Si

Ph

Ph

Ph

CBr2Ph Si

Ph

Ph

Ph

CO

Ph

NBS: N-bromosuccinimide

AgOAc

H2O

(78% yield)128

C

O

R S N

C

OH

R SiR2

R3

R1

C

O

R H

C

O

R NMe2

C

O

R SiR2

R3

R1

C

O

R OMeC

O

R Cl

SiR1

R2

CBrBr

R

R3

Scheme 50.

Chart.

Scheme 51.

d)


a. From α-silyl alcohols2,4

α-Silyl alcohols can be prepared by several methods,such as the condensation of trialkylsilyl anions withaldehydes85 and the transmetalation of trialkylstannanesfollowed by a reverse Brook rearrangement86. Theoxidation of a-silyl alcohol 129 with ordinary oxidizingreagents like permanganate and chromic acid leads toacylsilanes 130 (Scheme 52). However, this route hasseveral limitations since Si-C bond cleavage may compete(Scheme 53)2, and the products may suffer over-oxidationto carboxylic acids (Schemes 43 and 44). Very mildconditions, such as those present in Swern oxidation, arethe most indicated options. In the example showed inScheme 5487,3, the “reverse Brook rearrangement”(131→132), followed by a mild oxidation, is employedfor the synthesis of α,β-unsaturated acylsilanes 133.Silylalcohol 135, prepared by nucleophilic opening ofepoxide 134, was oxidized under extremely mild conditionby the use of the Dess-Martin reagent, giving acylsilanes

136 in good to excellent overall yields (Scheme 55)88.Recently, we have found that potassium permanganatesupported onto alumina transforms silylalcohols toaroylsilanes in good yields, without significant Si-C bondcleavage or over-oxidation to carboxylic acid89.

b. From masked aldehydes

The addition of silyllithium reagents to aldehydes givesα-silyl alcohols, which may be oxidised to acylsilanes ascommented above. However, aldehydes 137 are morecommonly converted into acylsilanes 139 by the dithianeroute (the umpolung methodology90, Scheme 56). Thehydrolysis of 2-silyl-1,3-dithianes 138 was first investigatedin simultaneous work by Brook91 and Corey92, and it isone of the most useful methodologies for acylsilanessynthesis. The great advantage of this method is the varietyof compounds that can be prepared, including aroylsilanes,alkanoylsilanes, and functionalized acylsilanes. In general,the first and second steps (Scheme 56) afford products in

R3Si CH

OH

R' [O]R3Si C

O

R'129 130

C

SiR'3

R

OHH

HO CrO

O

OH

C

SiR'3

R

OH OH

O

O

Cr H C

R

O R3SiOH-H2O

-H2CrO3

Scheme53H2O

R

R'

OSiMe3

LiR

R'

OHn-BuLi

Me3SiCl

R

R'

OSiMe3t-BuLi

R

R'

SiMe3

OLi

R

R'

SiMe3

OH

H3OR

R'

SiMe3

O[O]-Swern

131

132133 (64-79% overall yield)

R = H, n-C7H15; R' = H, CH3

O

Si(i-Pr)3

Nu-

NuSi(i-Pr)3

OH

[O]-De ss -Ma rtinNu

Si(i-Pr)3

O(7 1 -9 1 %) (7 2 -8 7 %)134 135 136

Scheme 52.

Scheme 53.

Scheme 54.

Scheme 55.


high yields, but the hydrolysis step may be problematic.Although there are many procedures for the regeneration ofthe masked carbonyl group in dithianyl compounds93, themost frequently applied reagents for 2-silyldithianes 138are mercury salts, the oldest methodology for hydrolysis.Generally, the hydrolysis with mercuric chloride is very slow,thus the product aroylsilanes may suffer degradation, asmentioned earlier. Other methods have been applied for theregeneration of the masked carbonyl group, givingacylsilanes in good yields. Among these, we may mentiontreatment with methyl iodide41, chloroamine-T33,I2/CaCO3

94, anodic oxidation95 and oxidative hydrolysismediated by N-bromosuccinimide (NBS)96.

The benzotriazole derivatives 140 present a similarapproach to the dithiane methodology, offering advantagein the hydrolysis step. The hydrolysis of intermediate 141occurs in situ and under mild conditions, giving the desiredaroyl, heteroaroyl, alkenoyl and alkynoylsilanes 142 inexcellent yields (Scheme 57)97.

c. From esters and amides

The synthesis of acylsilanes by reductive silylation

is well known and proceeds by the reaction of esters withsilyl-Grignard derivatives, forming silylacetals 143(Scheme 58)98. This method generally gives poor yieldsand hence has been seldom employed. One-pot synthesisof aroylsilanes based on reductive silylation ofmethylbenzoates using Mg/I2/chlorosilane/NMP(1-methyl-2-pyrrolidinone) affords aroylsilanes inmoderate yields99.

Compounds containing lithium attached to the siliconare extremely important reagents in organosilanechemistry. Dimethylphenylsilyllithium (144) is probablythe most useful silyllithium for synthesis, due to the arylgroup that gives good anion stability and to the fact thatthis reagent can be readily prepared from thecorresponding chlorodimethylphenylsilane by itsreaction with lithium in THF100. On the other hand,trimethylsilyllithium is readily obtained by the reactionof hexamethyldisilane with methyllithium101. Thesecompounds react with esters or amides to affordacylsilanes (Scheme 59)102. Amides appear to be moreuseful, giving better yields than the traditional reactionwith esters, which require much lower temperatures.

C

O

R HC

SS

R H

1. n-BuLiC

SS

R SiR'3

HS(CH2)3SH hydrolysisC

R SiR'3

O

138

BF3OEt2

137 139

2. R'3SiCl

BtH, HC(OEt)3,EtOH, THF

(57 - 97%)

R

N

OEt

N

N

R

O

HR

N

OEt

N

N

SiR'3HCl/H2O

r.t. R

O

SiR'3

R = aryl and heteroaryl ; substituted alkenyl and akynyl

140 141 142

THF, -78 oCr.t.

1. BuLi

2. R'3SiCl

(05 - 75%)

Ar

O

OMeMe3SiCl

Mg/HMPTC

OMe

Ar

SiMe3

O SiMe3H2O/HCl

Ar

O

SiMe3

MeOSiMe3

143

Scheme 56.

Scheme 57.

Scheme 58.

144

R

O

SiMe2PhPhMe2SiLiR

O

SiMe2PhR

O

NMe2 R

O

OMe

R = Me, C2H5 , t-Bu

-7 8 o C -1 10 o C(6 9 -9 1 %)

R = Me, Ph

(7 0 -76 %)

Scheme 59.

)


In general, the reaction of silyllithium with esters affordsdisilylalcohols as undesirable by-products due to doublenucleophilic attack at the carbonyl group. However, thesealcohols, such as 145, have been oxidized by PDC(pyridinium dichromate)102, tert-butyl hypochlorite103

and lead tetraacetate104 (Scheme 60) to the correspondingacylsilanes. This latter method was recently reported, andinvolves a “radical Brook rearrangement” providingacylsilanes in good yield after treatment with silica gel.

d. From S-2-pyridyl esters

S-2-Pyridyl esters 146 react very smoothly withAl(SiMe3)3 in the presence of CuCN to afford acylsilanesin good to excellent yields (Scheme 61). This method maybe applied to substrates having various groups such asalkoxyl, acetal, ester, or an isolated double bond. Chiralcenters α to the carbonyl group are not epimerized underthe reaction conditions105.

e. From acid chloride

Treatment of silyllithium with acid chloride gives

acylsilanes. However, this procedure is not general due to thecomplex reaction mixtures that it provides. On the other hand,lithium silylcuprates like 148 react with a variety of acidchlorides, giving acylsilanes with good yields, offeringadvantages over the silyllithium methodology since fewerby-products are formed106. These cuprates are traditionallyobtained from the reaction of an alkylsilyllithium with CuCNor CuI107. A limitation of this methodology is that high ordercuprates are very reactive towards a variety of functionalgroups. The mixed Cu-Zn complex 147 is less reactive thanordinary cuprates, and therefore this type of complex hasbeen applied to the synthesis of acylsilanes containing cyano,halo, ester and other groups (Scheme 62)6,108.

Yamamoto and co-workers109 prepared aroylsilanes byreaction of disilanes (compounds with Si-Si bond) withbenzoyl chloride under palladium catalysis. However thismethod is not suitable for aliphatic acylsilanes, givinglow yields of products. The methodology presented inScheme 63 is a good alternative, providing both aroyl andalkanoylsilanes by reacting the acid chlorides 149 withthe polarised Si-Sn bond of 150 (weaker than the Si-Sibond in the disilanes)110.

O

ORPhOH

SiMe2PhPh

PhMe2Si

1. Ph Me2SiLi THF

2. H2O SiMe2PhPh

O

145

Pb(OAc)4 OAc

SiMe2PhPh

PhMe2SiO SiO2

(94%)

(61-98%)

R = C9H19; Ph; PhCH=CH; TBDMSO(CH3)CH; BOMOCH2(CH3)CH; Ph(CH3)CH

R

O

SiMe3

Al(SiMe3)3

R

O

S N146

CuCN, THF, 0 oC to RT

R

O

Cl R

O

SiMe3

(Me3Si)2CuCNLi2(Me2PhSi)2CuCN(ZnCl)2

R

O

SiMe2Ph

147 148

(5 0 - 9 5 %) (4 0 - 8 7%)

Scheme 60.

Scheme 61.

Scheme 62.

R

O

Cl Me3SiSnBu310% (EtO)3P

R

O

SiMe3SnBu3Cl

(30-74%)

R = n-C4H9, n-C7H15, C4H9(Et)CH, c-C6H11, Ph, o-ClC6H4, p-CH3OC6H4

149 150

5% [(η3C3H5)PdCl]2

Scheme 63.

r.t.


f. From other organic functionalities

The application of α,β-unsaturated acylsilanes asbuilding blocks for organic synthesis is well known insuch important reactions as the Diels-Alder one111, thermalrearrangements and cyclizations, as commented above. Acommon method for alkenoylsilane synthesis goes throughthe allenylsilanes 151 and is known as Reich’s procedure(Scheme 64)113. Scheme 65 summarizes another methodfor the preparation of α-substituted-α,β-unsaturatedacylsilanes 155 from silylpropargyl derivative 152 in amethodology involving silyloxy allene formation, a“reverse Brook rearrangement” (153→154) followed bythe addition of an aldehyde.

Several methods for the preparation of haloacylsilanesare reported in the literature, such as bromination of silylenol ethers115 and halogenation of alkyl enol ethers116

with N-bromosuccinimide (NBS) or N-chlorosuccinimide(NCS). The reaction of ketones with silyl carbanion 156,

which is obtained from an ethereal solution of t-BuMe2SiCHBr2 and lithium diisopropylamide, providessilyloxiranes 157 which undergo rearrangement, yieldingα-bromoacylsilanes 158 in reasonable yields (Scheme66)117. This method is a recent example of an α-bromoacylsilane preparation, where the formation of 2-silyloxiranes 157 is proposed by the authors, based on aknown method for synthesis of α-iodo, α-fluoro, α-bromoand α-chloroacylsilanes 160 from silyloxiranes 159(Scheme 67)61.

Acylsilane 164 could be prepared in a one-potprocedure from vinyl ether 161 by the reaction ofintermediate 162 with trialkyl silyl chloride in pentaneat –78 oC, followed by mild acid hydrolysis of 163(Scheme 68)32,118. Starting with allylic alcohol 165,acylsilane 23 was prepared in a one pot procedure(Scheme 69)18. This acylsilane was used in the Corey’stotal synthesis of triterpenes as presented earlier inScheme 10.

HRSiOCH21. t-BuOK

2. t-BuLiC C CH2

RSiO

LiC C CH2

LiO

RSi

R'CHORSi

O OH

R'

152

R = TBDM (t-BuMe2) or TIP (triisopropyl)

(27-92%)153 154 155

157

158

156

TMEDA

O

t-BuMe2Si

Br

R

Rt-BuMe2Si C

Br

Br

C

R

OLi

REt2O

R2COt-BuMe2Si C

Br

Br

Li

(5 0 - 7 2 %)

R = P h, E t or -(CH2 )5 -

t-BuMe2Si

ORBr

R

Scheme 65.

Scheme 66.

1 .n-B uLi

2 . Me2 R S iCl

O O OEEMe2RSi

H2SO4

H2O

O

SiMe2R

151R = Me , t-B u

(8 1 -8 6 %) (6 5 -8 4 %)

Scheme 64.


OCH3 OCH3

Li

OCH3

SiR3t-B uLi/TMEDA

-7 8 o C

ClS iR3

-7 8 o C

HCl/Me OH

0 o C

O

SiR3

161 162 163 164

R = t-BuMe2, Et, n-Pr

OH

SiMe2t-BuO1 . Ms Cl, E t3 N, THF2 . LiB r, THF

3 . LDA,

SiMe2t-Bu

NOMe

4 . Na OAc-AcOH

165 23 (90 %)

Scheme 68.

Scheme 69.

6. a) Bonini, B. F.; Franchini, M. C.; Fochi, M.; Mazzanti,G.; Ricci, A. Gazz. Chim. Ital. 1997, 127, 619;b) Bonini, B. F.; Franchini, M. C.; Fochi, M.; Mazzanti,G.; Ricci, A. J. Organomet. Chem. 1998, 567, 181.

7. Nájera, C. Yus, M. Org. Prep. Proced. Int. 1995,27, 383.

8. Chieh, P. C.; Trotter, J. J. Chem. Soc. 1969, 1778.9. (a) Brook, A. G.; Warner, C. M.; McGriskin, M. J. Am.

Chem. Soc. 1959, 81, 981. (b) Brook, A. G. Acc. Chem.Res. 1974, 7, 77. (c) Brook, A. G.; Bassindale, A. R.In: Rearrangements in Ground and Exited States; deMayo, P., Ed; Academic Press, New York, 1980.

10. (a) Brook, A. G. J. Org. Chem. 1960, 25, 1072.(b) Brook, A. G.; Schwartz, N. V. J. Org. Chem. 1962,27, 2311.

11. Brook, A. G.; Vandersar, T. J. D.; Limburg, W. Can. J.Chem. 1978, 56, 2758.

12. Brook, A. G.; Yu, Z. F. Organometallics 2000, 19, 1859.13. Takeda, K.; Ohnishi, Y. Tetrahedron Lett. 2000, 41, 4169.14. Biernbaum, M. S.; Mosher, H. S. J. Org. Chem. 1971,

36, 3169.15. Hudrlik, P. F.; Hudrilik, A. M.; Kulkarni, A. K. J. Am.

Chem. Soc. 1982, 104, 6809.16. Nakada, M.; Urano, Y.; Kobayashi, S.; Ohno, M.

Tetrahedron Lett. 1994, 35, 741.17. (a) Bonini B. F.; Franchini, M. C.; Laboroi, F.;

Mazzanti, G.; Ricci, A.; Varchi, G. J. Org. Chem. 1999,64, 8008. (b) Bonini B. F.; Franchini, M. C.; Fochi,M.; Gawronski, J.; Mazzanti, G.; Ricci, A.; Varchi, G.Eur. J. Org. Chem. 1999, 437.

18. Huang, A. X.; Xiong, Z.; Corey, E. J. J. Am. Chem.Soc. 1999, 121, 9999.

19. Cirillo, P. F.; Panek, J. S. J. Org. Chem. 1990, 55, 6071.20. Cirillo, P. F.; Panek, J. S. J. Org. Chem. 1994, 59, 3055.

Conclusion

In this review we have resumed the most significantarticles, published in the last ten years, involvingacylsilanes, both from the point of view of their preparationand their application as versatile tools in organicsyntheses. The research in this area has increasedsignificantly over the last few years due to the discoveryof valuable new reactions and the improvement ofacylsilane synthesis methods. It is possible to visualisethat in the near future the acylsilanes will be a well-knowntool for the use of organic synthetic chemists.

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Y = Cl, Br, I or F

160 (4 9 -9 6%)

Metal salts: ZnCl2, ZnBr2, NaI, AgBF4

R = Ph, Me, t-Bu

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Scheme 67.


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Received: November 14, 2000Published on the web: February 10, 2001

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Acylsilanes and Their Applications in Organic ChemistryAmauri F. Patrocínio and Paulo J. S. Moran* Instituto de Química, Universidade Estadual de Campinas, CP 6154, 13083-970 Campinas