ORGANOMETALLIC COMPOUNDS IN ORGANIC SYNTHESIS

CATALYTIC

Advantages = 'Difficult Reactions'

Disadvantages = Cost, Enviromental

Low Cost Metals

STOICHEIOMETRIC

Advantages = Cost, Enviromental

Disadvantages = May not be possible

High Cost Metals / ComplexesTransition Metals

This presentation looks at the synthesis, reactivity and STOICHIOMETRIC use of...

MAIN GROUP ORGANOMETALLICS AND ORGANOTRANSITIONCOMPOUNDS WHICH ARE ALSO HIGHLY NUCLEOPHILIC (OR BASIC)SOURCES OF "R-"

in the order....

LiR, NaR, KR RMgX RTiX 3

RAlX2 ZnR2 Organoceriums Organosameriums

Organomanganese

RX excess Li

-LiXRLi

RHBuLi

-BuHRLi

ArBr BuLi

-BuHArLi

All Common !!

Also Grignards etc.

THINK !! - Don’t discount the unusual, e.g.........

O SPh

NMe2

Li

"LIDMAN"

O Li

T. Cohen and T. R. Matz, Synth. Commun., 1980, 10 , 311.S. Bank, M. Platz, Tetrahedron Lett. 1973, 14 , 2097

Structures. Hydrocarbons C6H6 Et2O THF

(RLi)n

# Solvent Polarity

# Steric

# S -hybridization

# delocalisation

EtLi

BuLi

Me3SiCH2Li

i-PrLi

sec-BuLi

tert-BuLi

6 4 4

6 4 4

6 4

4

4

4 2 2 / 1

Solvent Effects

BunLi Et2O

OO

O

O

Temp. for t1/2 (dec.)= 100 h

0C -50C -100C

Li O

NR2

X

X = C(O)NR2

BuLi

BuLi

X = H

N/R unless

NMe2Me2N

Li

V. Snieckus, Chem.Rev. 1990, 90 , 879-933.

Metal Basicity vs Nucleophilicity and Reductivityy

Metal Basicity vs Nucleophilicity and Reductivityy

"CH3 M +

" +R

O

R

H Hpka 4.2

R

O

R

H

R

H H

O

M

Me

ROR

• Gas-phase Basicity

• CH3- CH4 0 KCH3 CH4 20 NaCH3 CH4 40 LiCH3 CH4 60 CH3MgBr CH4 80

• in K cal mol-1

Metal Effects - IMetal Effects - I

K 100 : 0

Na 94 : 6

Li 84 : 16

MgBr 0 : 100

PhMMe

O

MePh

Ph

O

M

+

O

Ph

M

Metal Effects - IIMetal Effects - II

BuLi + But OK- 40 C

o

BuK

Strong Base

+ LiOBut

K

LiBr

Li

- 35 Co

Metal Effects - IIIMetal Effects - III

CO2

+

CO2MM

CO2

EMg

X

Strong

low e -density

K 10 : 90

MgBr 99 : 1

Metal Acidity vs. Reactivity and Selectivity

Metal Acidity vs. Reactivity and Selectivity

H

CO

O

OMeMBr

H

C

OO

Me

MeLi

N/R

via H

O

O

Mg

Me

BrO

+

_

Affects * Substrates that form carbocation

* Strong Lewis acid metal complexes (Zn, Mg,Ti, Al etc.)

TITANIUMTITANIUM

RMTransmetallation

Cl TiX3

R TiX3

X = Cl More Lewis Acidic

= OR, NR2 Less Lewis Acidic

M = Li, Mg, Zn

* TiCl4 limited to MeLi, ZnMe2, C3H5Li, resonance stabilisedcarbanions

* X3Ti-R, R is not stable if - hydrogen(s) present( e.g. Et )

Problems

MeTi(OPri)3 < Me2Ti(OPr

i)2 < Me3Ti(OPr

i)

TiCl4 Ti(OPri)4+ 3

RM

Cl Ti(OPri)3

R Ti(OPri)3R

O

H

O

C

R

OHC

RO

Selective for Aldehydes

Cram Selectivity :Cram Selectivity :

M S

L

CHO

Favoured

MR

R

OH

H

H

Ph

Me

R

OH

H

H

Ph

Me+

MeMgBr 66 : 34

MeTi(OPri)3 90 : 10

PhSO2CH2Ti(OPri)3 65 : 35

Enantioselectivity :Enantioselectivity :

R

OH

68-98 % e.e.

O

Ph Ph

O

PhPh

H

H

O

O

TiR

X

Ar H

O

R = Me

X = OPri

R H

O

R = allyl

X = Cp

Ar

OH

Me

H

70-95 % e.e.

Olefination Reaction :Olefination Reaction :

O

CH2Br2 / Zn / TiCl4

83 %

( 10 % with Ph3P=CH2 )+

iPr Pri

OTiCl3(DME)1.5

Pri

Pri

Pri

Pri

87 %

( 12 % with TiCl4 / LAH )

Zn

But what is the mechanism .... ?

ALUMINIUMALUMINIUM

MeLi 79 21MAD/MeLi 1 99

S. Saito and H.Yamamoto, JCS Chem. Commun., 1997, 1585.

2

OH

AlMe3O

AlO

Me

'MAD'

OOH

Me

Me

OH+

OAlX3

R

ZINC I : Synthesis

ZINC I : Synthesis

Klement et al. Tetrahedron Lett., 1994, 35 , 1177-1180.P. Knochel and R. D. Singer Chem. Rev., 1993, 93 , 2117-2188.

Source Problem

ZnEt2 Comercial only one !

ZnX2 + RM Getting ZnX2 dry !

ZnEt2 + RI Getting rid of EtI

R MLn

Br

ZnEt2

RZnBrMLnEt

EtH2C=CH2+

EtH

MLn

RBr

CuCl + MnBr2CuX

M = Mn, Cu

ZINCII : UseZINC

II : Use

R. Noyori, Chem. Soc. Rev., 1989, 18 , 187-208.

ZnEt2

Ar H

O

R2

N

OH

ZnEt2 +

N

O

R2

Zn

O

Et

Ar

H

Slow

NR2

Zn

O

Et

Ar

H

ZnOO

Et2

NR2

Zn

OAr

H

ZnOEt2

99 % ee

OZnEt

HAr

Et

CERIUMHydride Reductions - I

CERIUMHydride Reductions - I

NaBH4-CeCl3

O HO H O

VS.

Sole Product

Via.

(MeO)nHmB H C O H O Me

Ce3+

CERIUMHydride Reductions - II

CERIUMHydride Reductions - II

LiAlH4 CeCl3

RX

RH

X = Cl, F

R = Alkyl, Aryl

NOH NH2

NaBH4PR3

O

BH3

PR3

PR3

O

PR3

..

CERIUMOrganocerium Reagent

CERIUMOrganocerium Reagent

BuCeCl2

BuLi+ CeCl3OH Bu

Ph Ph

O

Ph Ph

96 %(33 %)Si

H

.

O

Si

O

Bu

91 %

Me

Bu

HO

MeO

NH2

BuBu

Ph

PhCN

57 %(< 10 %)

SAMARIUMSAMARIUM

SmI2

RX

RH

O

R

R'R'

OR2

O

R

R'R'

H2

R Cl

O

R' R'

OR

O

R'R'

OH

RCN

R NH2

RCO2H

R OH

R R

O

R'I

R R'R

OH

ROH

( )n

I R

O

( )n

RX

XYI--NC

R SmX2

N

XYI

R R

O

OH

RR

OH

RR

SAMARIUMSAMARIUM

H. Yasuda et al. J. Am. Chem. Soc., 1992, 114 , 4908

XSCO2Me

Me

Me

CO2Me

CO2Me

Me

O

MeO CH2

Me

H

Cp2Sm*

O

MeO

O

MeCH2 H

CH2

OMe

O

Cp2Sm*

Sm

HCp*

HCp*

Sm

Cp*

Cp*

OMe

O

2

O

OMe

MANGANESEOrganomanganese - I

MANGANESEOrganomanganese - I

G. Catiez and M. Alami Tetrahedron , 1989, 45 , 4163-4176.

Mn + I2 MnI2

LiRLiMnR3

10 to 30 C

R2MnRMnX

5 C

Li2MnCl4LiCl +MnCl2

~

RLi Or RMgX

MANGANESEOrganomanganese - II

MANGANESEOrganomanganese - II

RMnX

CuCl

CHO

R

CHO

R' O R'

O O

R R'

O

Cl R'

O

R R'

O

Me COCl

OH

O

Me

OH

O

R

O

CuX

O

O

R

84% c.y.

98% e.e.