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Synlett 2010(1): 134-136  
DOI: 10.1055/s-0029-1218541
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Convenient, Highly Stereoselective, Metal-Free Synthesis of Chiral Amines

Stefania Guizzetti*a, Maurizio Benaglia*a, Cinzia Biaggia, Giuseppe Celentanob
a Dipartimento di Chimica Organica e Industriale, Universita’ degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy
Fax: +39(0250)314159; e-Mail: maurizio.benaglia@unimi.it;
b Dipartimento di Dipartimento di Scienze Molecolari Applicate ai Biosistemi, Università degli Studi di Milano, Via Golgi 19, 20133, Milano, Italy
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Publication History

Received 6 October 2009
Publication Date:
09 December 2009 (online)

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Abstract

A low cost, efficient, metal-free highly stereoselective reduction of ketimines to chiral amines was developed. Different imines bearing a very cheap and removable chiral auxiliary were reduced simply by trichlorosilane in the presence of N,N-dimethyl­formamide, often in quantitative yield and complete control of the absolute stereochemistry, to afford highly enantiomerically enriched amines.

Key words

imine reduction - Lewis base - trichlorosilane - chiral auxiliary - chiral amine

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15

Typical Experimental Procedure for the Reduction of Ketimines
To a stirred solution of the imine (1 mmol/equiv, for the imine synthesis see Supporting Information) in CH2Cl2 (2 mL), DMF (6 mmol/equiv) was added. The mixture was then cooled to -50 ˚C and HSiCl3 (3 mmol/equiv) was added dropwise by means of a syringe. The reaction was quenched by the addition of NaHCO3 sat. soln (2 mL). The mixture was allowed to warm up to r.t. and H2O (2 mL) and CH2Cl2 (5 mL) were added. The organic phase was separated and the combined organic phases were dried over Na2SO4, filtered, and concentrated under vacuum to afford the crude product.