Organolithium enantioselective additions

Organolithium Reagents/Sparteine Combinations as Chiral Nucleophiles for Enantioselective Additions... 

Goldfuss B (2003) Enantioselective Addition of Organolithiums to C=0 Groups and Ethers. 5 12-36... 

The enantioselective addition of the amino organolithium reagents consists of two stereo-controlled reactions, the asymmetric deprotonation (equation 14) and the following addition to electrophiles. The stereochemical course of the addition depends on the electrophile E. In the cases where heterocyclic enone or a,-unsaturated lactones are the electrophiles (entries 5-7), the addition proceeds with retention of configuration. In contrast, with the other electrophiles in Table 10 and trimethyltin chloride in equation 15, the addition proceeds with inversion of configuration. In the addition which proceeds with retention of configuration, a pre-complexation between the electrophiles and lithium may be involved (equation 16). 

Notable is the general enantioselective addition of organolithiums to chiral vinyloxazolines (38) in which the intermediate azaenolate (39) can be further alkylated with high diastereoselectivity (Scheme... 

Enantioselective Addition of Functionalized Organolithi-ums to Aldehydes. Amino alcohol (1) is a chiral ligand for various functionalized organolithiums derived from acetonitrile and A -nitrosodimethylamine (eq 4). 

The pyrrolidine derivative (104 equation 24) developed by Mukaiyama and cowoikers for the enantioselective addition of organolithiums to aldehydes has been one of the most studied. Although opti-... 

Table 29 Enantioselective Additions of Organolithium Reagents (RLi) to Benzaldehyde in the Presence of (108)...

The first report of an external chiral ligand-mediated enantioselective addition of an organolithium reagent to an imine appeared in 1990 (Tomioka, in this volume) [27]. Tomioka and coworkers found that 1,2-addition of MeLi, n-BuLi and vinyllithium to the 4-methoxyphenylimine of benzaldehyde 15 gave, in the presence of tridentate aminoether 16, the corresponding tertiary amines 17 in excellent yields and good ees (71-77%) (Scheme 6). 

Enantioselective additions of organolithiums to aldehydes are employed to synthesize chiral secondary alcohols, but these reactions are also quite frequently used for testing new chiral ligands and additives. The latter is usually performed with the standard addition of organolithium reagent RLi, in many cases n-butyllithium, -BuLi) to benzaldehyde [Eq. (1)], L denotes a chiral ligand] [9, 15,17-19]. 

Despite the frequent employment of n-BuIi in enantioselective additions, only very few complexes of n-BuLi (or other organolithiums) and chiral, enanti-opure hgands have been structurally analyzed. WilHard et al. reported in 1997 X-ray crystal structures of mixed complexes of n-, i-, and f-butyllithium with hth-iumM-isopropyl-O-methylvahnolate (17,Scheme 2) [72].The 2 1 stoichiometry of the mixed aggregates in the sohd state was also found in solution with noncoordinating solvents such as hexane or toluene [73]. 

Enantioselective additions of organolithiums to prochiral ketones yield tertiary chiral alcohols, which are a synthetically highly attractive class of substances [85]. The formation of enolates via deprotonation (of a-hydrogens in the sub-... 

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