Organolithium compounds enantioselective addition

As with the reduction of aldehydes and ketones (16-23), the addition of organometallic compounds to these substrates can be carried out enantioselectively and diastereoselectively. Chiral secondary alcohols have been obtained with high ee values by addition to aromatic aldehydes of Grignard and organolithium compounds in the presence of optically active amino alcohols as ligands. ... 

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. 

Compound 388 is an acylating agent for electron-deficient alkenes, in a Michael addition process. It is formed by treating molybdenum hexacarbonyl with an organolithium compound, followed by quenching the intermediate 387 with boron trifluoride (equation 104). The structure of 388 (R = Ph) can be elucidated by NMR spectroscopy. Other examples of enantioselective and diastereoselective Michael-type additions involving lithium-containing intermediates in the presence of chiral additives can be found elsewhere in the literature . 

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). 

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)]. 

When the protocol is applied to allylcarbamates 170, the deprotonation in the presence of (—)-sparteine does not occur with kinetic preference. Indeed, a dynamic resolntion by crystallization takes place. The epimeric allylfithinm componnds 171 and 172 are eqni-librating, whereby one of them crystallizes predominantly. Under optimized conditions, when n-butyllithium is used for the deprotonation and cyclohexane serves as a cosolvent, the preference of the diastereomer 172 leads to snbstimtion products in 90-94% gg393-395 enantioselective homoaldol reaction has been developed based on this protocol Transmetalation of the organolithium into the titaninm compound occnrring nnder inversion of the configuration (172 173) and subseqnent addition to aldehydes leads to... 

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