Enantioselective Aza-Henry Reaction Catalyzed by a Bifunctional Organocatalyst

Abstract

[reaction: see text] The aza-Henry reaction of imines with nitroalkanes was promoted by chiral thiourea with an N,N-dimethylamino group to give beta-nitroamines with good enantioselectivity. Various N-protected imines were examined as substrates. N-Phosphinoylimine gave the best result in terms of chemical yield and enantioselectivity (up to 91% yield, up to 76% ee).

Development of Chiral Thiourea Catalysts and Its Application to Asymmetric Catalytic Reactions

“…Although the catalyst efficiently accelerated a variety of asymmetric reactions such as Michael addition, aza-Henry reaction, Mannich reaction, and hydrazination as a result of dual activation of electrophile and nucleophile, [81][82][83][84][85][86][87][88][89][90] the scope of suitable nucleophiles for catalysts 2a was mainly limited to active methylene compounds. We therefore turned our attention toward the development of new catalysts having coordinating or chelating functionality, which might activate metallic nucleophiles.…”

“…In this review, we provide a comprehensive overview of our recent studies on bifunctional thiourea-mediated asymmetric nucleophilic reactions. [81][82][83][84][85][86][87][88][89][90] …”

Synthesis and Crystal Structure of 1-(3-fluorophenyl)-3-(3,4,5-trimethoxybenzoyl)thiourea

“…Thioureas have widely been used in enantioselective synthesis, such as in nitro-Mannich reactions, aza-Henry reaction, and the Michael Addition [8]. Symmetrical and asymmetrical phenethyl thioureas, 5-halo-substituted thiophene pyridyl thioureas and heterocyclic thioureas are non-nucleoside inhibitors of HIV-1 reverse transcriptase [9]. Condensation of thiourea derivatives with carbonyl compounds have been used in the synthesis of 1-aroyl-3-aryl-4-substituted imidazole-2-thiones [10], 2-(aroylimino)-3-aryl-4-methyl/phenyl-1,3-thiazolines [11].…”

Crystal Structure of N-[(1-Hydroxy-3-phenylpropan-(R,S)-2-yl)carbamothioyl]-3-nitrobenzamide

“…5 In addition, thioureas have been shown to possess antibacterial, antifungal, antitubercular, antithyroid and insecticidal properties. 6 Also, these compounds have been widely used in enantioselective synthesis, [7][8][9] such as in nitroMannich reactions, the aza-Henry reaction, and Michael addition. In this paper, we show the crystal structure of N-[(1-hydroxy-3-phenylpropan-(R,S)-2-yl)carbamothioyl]-3-nitrobenzamide.…”