Copper-Grignard complexes, conjugate

Sakai and co-workers [38] studied the additions to conjugate esters protected with a cyclic diol as a chiral auxiliary. The ester is protected with enantiomerically pure ( R2R) rrfl/js-cyclohexane diol (see Table 4, entry 7). Addition of phenyl Grignard reagent, catalyzed by Cul, produced a moderate yield (50%) of a mixture of the two diastereomers (prochiral carbon R/5 = 78% 22%) with a d.e. of 55%. In contrast, the authors also reported that addition of the phenyl lithium cuprate gave 94 6 ratio with the major product having the S-configuration for the prochiral carbon. Because of the differences in the structures of the complexes, attack from the lithium cuprate comes from the Re-face, whereas attack from the copper-Grignard comes from the Si-face. 

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. 

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