Highly Active Organocatalysts for Asymmetric anti‐Mannich Reactions

Abstract

Lighten the load! A family of enantiopure 4-oxy-substituted 3-aminopyrrolidines arising from the enantioselective ring-opening of meso-3-pyrroline oxide have been developed as catalysts for the asymmetric, anti-selective Mannich reaction (see scheme; PMP=p-methoxyphenyl; PG=protecting group). Very high catalytic activity (down to 0.01 mol % loading) and stereoselectivity have been recorded.

Efficient Synthesis of 3,3‐diaryloxindoles Catalyzed by L‐prolinate Anion Immobilized onto Amberlite as a Novel Heterogeneous Organocatalyst

“…The interest in this field has thus increased spectacularly in the last few years. 10 It is noticeable that the immobilization methods for the heterogenization of L-proline require the use of synthetic materials that are more expensive than proline or need tedious experimental methods. L-proline is commercially available at low cost but often employed at high catalyst loading.…”

Density functional study of organocatalytic mannich-type reactions: Insight into reverse diastereoselectivities arising from catalysts with different scaffolds

“…The asymmetric Mannich reaction is a powerful CC bond‐forming reactions that are used for the construction of enantiomerically enriched amino acids, amino alcohols, amino carbonyls, and their derivatives . Considerable efforts in particular in organocatalysis have been made for the development of catalytic asymmetric Mannich reactions over the last decade and various metal‐free chiral catalysts have been designed for this reaction . For these organocatalyzed asymmetric Mannich and Mannich‐type reactions, both syn ‐ and anti ‐selective routes that generate products with good enantioselectivity for various substrates of aldehydes and ketones have been reported.…”

“…Hence, in these proline (or derivatives) and acyclic α‐amino acid‐catalyzed asymmetric Mannich‐type reactions with unmodified carbonyl compounds, two new stereocenters created in a single step have been limited with high syn ‐diastereoselectivity. While, the problem of the syn ‐selective Mannich reactions is well solved, for achieving different isomers in the asymmetric synthesis process, the corresponding anti ‐selective organocatalytic asymmetric Mannich‐type reactions has received increased attention . Córdova and Barbas reported the first ( S )‐2‐methoxymethyl‐ pyrrolidine (catalyst V )–promoted highly anti ‐selective Mannich‐type reactions of unmodified aldehydes with performed imine of ethyl glyoxylate.…”

Solvent-controlled diastereoselectivity in tryptophan-catalyzed Mannich reactions

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still yet to be developed [23][24][25][26][27][28][29][30][31][32]. In particular, none of the presently known catalysts, with the possible exception of O-(tert-butyl)-L-threonine, [28] are suitable for the stereocontrolled preparation of anti-Mannich adducts derived from hydroxyacetone (1).

In the course of a research program devoted to spontaneous mirror-symmetry breaking and asymmetric organoautocatalysis, [33][34][35][36][37][38][39][40] we needed to prepare both the syn (3a) and the anti (3b) stereoisomers of the Mannich adduct from hydroxyacetone (1) and the glyoxylate-derived imine 2.

…”

“…still yet to be developed [23][24][25][26][27][28][29][30][31][32]. In particular, none of the presently known catalysts, with the possible exception of O-(tert-butyl)-L-threonine, [28] are suitable for the stereocontrolled preparation of anti-Mannich adducts derived from hydroxyacetone (1).…”