Michael addition metal prolinate

Org. Lett. 1999, 1, 157 d) Baylis-Hillman reaction Y. Iwabuchi, M. Nakatani, N. Yokoyama, S. Hatakeyama, J. Am. Chem. Soc. 1999, 121, 10219 e) Michael-Addition using alkali metal salts of proline M. Yamaguchi, T. Shiraishi, M. Hirama,... 

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... 

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. 

A typical procedure for the Michael addition catalyzed by metal prolinate According to the literature, under an argon atmosphere, to a mixture of di(tert-butyl) malonate (0.88 mL, 4.5 mmol), 2-cyclohexen-l-one (0.25 mL, 2.5 mmol) in CHCI3 (2mL), L-proline rubidium salt (100 mg, 0.50 mmol), and CsF (70 mg, 0.50 mmol) were added, and the mixture was stirred vigorously at room temperature for 48 hours. The reaction was then treated with 2-M HCl and was extracted twice with ethyl acetate. The combined extracts were washed with brine, dried (Na2S04), filtered, concentrated, and fiash chromatographed over silica gel, giving the (i )-(+)-adduct (658 mg, 84%) with 65% ee. 

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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