Grignard reagents asymmetric reactions

Asymmetric synthesis by the catalytic cross-coupling reaction has been studied most extensively with secondary alkyl Grignard reagents. Asymmetric cross-coupling with... 

The Kulinkovich reaction is the titanium-catalysed synthesis of cyclo-propanols from carbo ylic esters and Grignard reagents. The reaction is very diastereoselective, and an asymmetric variant was described by Corey et al. in 1994, by using the spirotitanate 79 (Scheme 7.48). Since this work, only a few titanium-catalysed asymmetric syntheses of cyclopropanols were reported, with enantiomeric excesses never higher than 80%. ... 

The carbonyl carbon of an unsymmetrical ketone is a prochiral center reaction with a Grignard reagent 2 (R 7 R, R") can take place on either face of the carbonyl group with equal chance. The products 8a and 8b are consequently formed in equal amounts as racemic mixture, as long as no asymmetric induction becomes effective ... 

Geranyltrimethylsilane, 142 Grignard cross-coupling, asymmetric, 31 Grignard reaction, 39,63 Grignard reagent, 45,58,120,121... 

Mikolajczyk and coworkers have summarized other methods which lead to the desired sulfmate esters These are asymmetric oxidation of sulfenamides, kinetic resolution of racemic sulfmates in transesterification with chiral alcohols, kinetic resolution of racemic sulfinates upon treatment with chiral Grignard reagents, optical resolution via cyclodextrin complexes, and esterification of sulfinyl chlorides with chiral alcohols in the presence of optically active amines. None of these methods is very satisfactory since the esters produced are of low enantiomeric purity. However, the reaction of dialkyl sulfites (33) with t-butylmagnesium chloride in the presence of quinine gave the corresponding methyl, ethyl, n-propyl, isopropyl and n-butyl 2,2-dimethylpropane-l-yl sulfinates (34) of 43 to 73% enantiomeric purity in 50 to 84% yield. This made available sulfinate esters for the synthesis of t-butyl sulfoxides (35). 

In 1999, Ikeda et al. reported a new type of sulfur-oxazoline ligands with an axis-fixed or -unfixed biphenyl backbone prepared in good yields by coupling reactions of methoxybenzene derivatives substituted with a chiral oxazoline and a sulfur-containing Grignard reagent. These ligands were subsequently evaluated for the test palladium-catalysed asymmetric allylic alkylation... 

This work was initiated in 1988 when Villacorta et al.71a reported the asymmetric conjugate addition of a Grignard reagent to 2-cyclohexenone. This study showed that 1,4-adducts with 4-14% ee were obtained in the presence of aminotroponeimine copper complex.713 Enhanced results (74% ee) were obtained by adding HMPA or silyl halides.71b Several other copper complexes were also used for inducing asymmetric conjugate addition reactions. Moderate results were obtained in most cases when THF was used as the solvent and HMPA as the additive. 

Modified MPV-type reductions carried out with chiral magnesium alkoxides and with chiral Grignard reagents have been discussed in detail (1). These reagents differ from the aluminum alkoxides since the Grignard reaction is essentially irreversible. Chiral alkali metal alkoxides have also been used to effect asymmetric reductions (1). 

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