Rubidium catalysts Michael addition

In order to broaden the scope of the amine-catalyzed Michael addition, Yamaguchi examined the system of amine and alkali metal salt [2]. Although amine did not promote the addition of malonate to enones, the LiCl04-Et3N catalyst turned out to be effective. Optically active amines, however, gave racemic adducts. As an extension, the (S)-proline rubidium salt, (S)-21, was developed, which possessed a cation and an amine moiety in the same molecule [2, 22]. The catalyst (S)-21 in chloroform promoted the asymmetric addition of malonate to a wide range of enones and enals as exemplified by the reaction of... 

Yamaguchi s pioneering report on asymmetric Michael addition of nitromethane to cyclic ketones catalyzed by proline rubidium salt [58], Hanessian and Pham [59] developed the first organocatalytic system for such a reaction where proline and trans-2,5 -dimethy Ipiperazine 64 additive were used as the catalyst. Later on, with the same additive, improved selectivities were obtained when using pyrrolidine-tetrazole 61 [60] and tra i-4,5-methano-L-proline 62 [61] as the organocatalyst. In 2008, multifunctional primary amine 63 [62] was also proved to be effective catalyst for such a reaction (Scheme 5.31). 

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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