Enantioselective Organocatalytic Reduction of β‐Trifluoromethyl Nitroalkenes: An Efficient Strategy for the Synthesis of Chiral β‐Trifluoromethyl Amines |
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| Authors: | Elisabetta Massolo Prof Maurizio Benaglia Manuel Orlandi Dr Sergio Rossi Giuseppe Celentano |
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| Affiliation: | 1. Dipartimento di Chimica, Universita' degli Studi di Milano via Golgi 19, 20133 Milano (Italy), Fax: (+39)?0250314159;2. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli, 25, Milano (Italy) |
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| Abstract: | An efficient organocatalytic stereoselective reduction of β‐trifluoromethyl‐substituted nitroalkenes, mediated by 3,5‐dicarboxylic ester‐dihydropyridines (Hantzsch ester type), has been successfully developed. A multifunctional thiourea‐based (S)‐valine derivative was found to be the catalyst of choice, promoting the reaction in up to 97 % ee. The methodology has been applied to a wide variety of substrates, leading to the formation of differently substituted precursors of enantiomerically enriched β‐trifluoromethyl amines. The mechanism of the reaction and the mode of action of the metal‐free catalytic species were computationally investigated; on the basis of DFT transition‐state (TS) analysis, a model of stereoselection was also proposed. |
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| Keywords: | bifunctional catalyst chiral fluorinated amines nitroalkenes reduction trifluoromethyl derivatives |
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