A Catalytic Enantioselective Michael Addition of a Simple Malonate to Prochiral α,β‐Unsaturated Ketoses and Aldehydes

Abstract

Distinct progress has been made in the catalytic asymmetric Michael addition of prochiral enolates to acceptors for example, enantioselective addition of indane-I-one-2-carboxylate to methyl vinyl ketone."I These reactions rely on the differentiation of donor enantiofaces by chiral catalysts. In contrast, very little success has been achieved in the enantioselective Michael addition of an enolate to prochiral acceptors, despite the high potential of this reaction to produce various chiral carbon centers."' The conventional methods appear to be highly substrate specific, and enantiomeric excesses attained have generally not been high. We disclose herein the first catalytic asymmetric Michael addition of a simple malonate ion to prochiral enones and enals, which employs the readily available rubidium salt of L-proline @).I3' The optical yields are substantial for this type of reaction, and the method can be applied to a range of acceptors to give adducts of predictable absolute configurations.The Michael addition of dimethyl malonate in methanol catalyzed by the lithium salt of L-proline gave race mate^.[^^ However, appreciable asymmetric inductions were observed when the reactions were carried out in chloroform. Furthermore, the rubidium salt 215] was found to possess remarkably high catalytic activity compared with the lithium salt, and higher optical yields were attained with diisopropyl ester lr6] (Scheme 1). Enantioselectivities up to 77% ee were

Michael Additions of Methylene Active Compounds to Chalcone in Ionic Liquids without any Catalyst: The Peculiar Properties of Ionic Liquids

“…[1][2][3][4][5] The catalysts used include different bases, such as the rubidium salt of l-proline. [6][7][8] Organocatalysts have also been used for Michael additions of aldehydes and ketones to unsaturated carbonyl derivatives or nitrostyrenes. [9][10][11][12][13][14][15][16] Reactions are usually carried out either in DMSO or by using an excess of one reagent as the solvent.…”

Facile and Efficient Enantioselective Strecker Reaction of Ketimines by Chiral Sodium Phosphate

“…[3] Meanwhile, there are comparatively few reports about chiral sodium salts and other alkali-metal salts in asymmetric synthesis. [4] In our earlier work in developing chiral alkali-metal salts, bifunctional sodium phenylglycinate was developed for the enantioselective cyanosilylation of ketones (Scheme 1; 1).…”

“…However, to the best of our knowledge, a direct catalytic asymmetric Strecker reaction catalyzed by a chiral alkali-metal salt has not yet been described. Recently, a chiral alkali-metal salt, [3,4] a sort of anionic Lewis base, [5,6] has been uncovered as a potential means for catalytic asymmetric reactions. Remarkable progress has been made in the asymmetric additions of trimethylsilyl nucleophiles with such anionic Lewis bases.…”

Asymmetric Organocatalytic Reactions of α,β-Unsaturated Cyclic Ketones

“…Yamaguchi group's pioneering work in the 1990s introduced L-proline rubidium salt as a catalyst for the addition of diisopropyl and di-tert-butyl malonates to cyclic enones with low to good enantioselectivities (35-88% ee) [17,18]. Then List and co-workers treated a mixture of acetone and L-proline (35 mol %) in DMSO with cyclohex-2-en-1-one [19].…”