Organolithium compounds asymmetric addition

Organolithium compounds are highly reactive and have been used in a variety of organic transformations. A major problem in the development of catalytic asymmetric conjugate additions of organolithium reagents to a,/3-unsaturated carbonyl compounds is that the high reactivity of RLi may cause both low chemoselectivity (1,2- vs. 1,4-addition) and low enantioselectivity. 

Asymmetric deprotonation of the achiral oxazolidine iV-Boc-4,4-dimethyl-l,3-oxazolidine with s-BuLi-(—)-sparteine affords a lithium derivative that adds unselectively to aldehydes. However, the transmetalation from lithium to magnesium, and addition of the resulting Grignard to benzaldehyde occurs with 90% diastereoselectivity and 93% enantioselectivity. The authors speculate that deprotonation and lithiation occur stereoselectively to give the R organolithium compound, and subsequent transmetalation and addition to benzaldehyde proceed with retention (Scheme 40). 

Several chapters deal with the synthesis of and the synthetic applications of organolithium compounds such as orthometallation, arene catalysed lithiation, addition to carbon-carbon double bonds, their reaction with oxiranes, and asymmetric deprotonation with lithium (-)-sparteine. We gratefully acknowledge the contributions of ah the authors of these chapters. 

The asymmetric addition of organomagnesium and organolithium reagents to a,P-unsaturated carbonyl compounds and especially imines can be achieved in situations where rigid chelation controls the geometry of the transition state. Stereospecific alkyl addition occurs in the case of a chiral leucine-derived imine to provide overall asymmetric alkyl addition to an a,P-unsaturated aldehyde (Scheme 107).380 381... 

Addition of organolithium compounds to chiral ( )-configured a, -unsaturated iron acyl complexes (116) proceeds with an exceptionally high degree of asymmetric induction.127-132 The initially formed... 

Since benzyUithium compounds having no adjacent heteroatom are configurationally labile [93], their enantioselective reactions may proceed through an asymmetric substitution pathway. In 1971, Nozaki and coworkers commented in the first enantioselective reaction of benzyllithiiun compounds that the enantiomeric ratio of organolithium compounds might be influenced by a chiral additive [94]. Deprotonation of ethylbenzene was performed with n-BuLi-(-)-sparteine at 70°C, followed by carboxylation at -65°C [Eq. (39)]. 

Enantiomerically pure alkylboranes arc known to be excellent reagents for asymmetric reduction but they can also be used to generate enantiomerically pure /V-borylimines by partial reduction of nitriles. Addition of organolithium and Grignard reagents to these compounds affords secondary carbinamines in moderate to good yield but low enantioselectivity13,14. The best results reported so far are shown below. 

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