Metal prolinate, enantioselective Michael addition

The products are versatile auxiliaries not only for enantioselective deprotonation and elimination (Section C.), but are also valuable chiral ligands for complex hydrides in the enantioselective reduction of ketones (Section D.1.4.5.)- They are also applied in enolate reactions (Section D.l.5.2.1., D.1.5.2.4.). transition-metal-catalyzed Michael additions (Section D.l.5.8.), 1,3-dipolar cycloadditions (Section D.l.6.1.2.1.), and additions ofGrignard reagents (Section D.l.3.1.4.2.5.). (5 )-2-(Phenylaminomethyl)pyrrolidine has found most application and is also commercially available. Several methods exist for the preparation of such compounds. Two typical procedures for the synthesis of (.S)-2-(l-pyrrolidinylmcthyl)pyrrolidine are presented here. The methodology can be readily extended to other amides and alkylamino derivatives of proline. 

In 1993, Yamaguchi reported an important milestone in the use of chiral amines as catalysts for enantioselective conjugate addition reactions (Equation 22) [114, 115]. The rubidium salt of proline (120) proved particularly ef ficient by comparison to proline or to its other metal salts. In the course of studies aimed at optimizing the process, beneficial effects were observed in the presence of CsF as an additive. This procedure led to the production of Michael adduct 121 from enone 118 in 88% ee [115]. 

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