Trichlorosilane‐Mediated Stereoselective Reduction of C=N Bonds

Abstract

The reduction of C=N bonds represents a powerful and widely used transformation allowing new nitrogen‐containing stereocenters to be generated. Chiral amino groups are ubiquitous in a variety of bioactive molecules such as alkaloids, natural products, drugs, and medical agents, so the development of a catalytic stereoselective process for the preparation of enantiomerically enriched amines through ketoimine reduction is attracting increasing interest, especially in view of future industrial applications. Great efforts to develop efficient organocatalytic methods to perform enantioselective imine reductions and reductive amination processes have recently been made. In the last few years, trichlorosilane‐mediated reductions have received constantly increasing attention because the potential to generate chiral catalysts for imine reduction simply by coordination of HSiCl3 with a chiral Lewis base has allowed the development of several efficient organocatalytic systems. Here we offer a complete overview of different chiral promoters of stereoselective reductions with trichlorosilane, classified as N‐formyl derivatives, which may be considered historically the first class of compounds developed as chiral activators of trichlorosilane, picolinamide derivatives, and miscellaneous compounds presented in that order.

Cinchona‐Derived Picolinamides: Effective Organocatalysts for Stereoselective Imine Hydrosilylation

“…[3] On the other hand, Lewis base based organocatalysts have been exploited with success in the stereoselective trichlorosilane-mediated reduction of N-substituted ketoimines [4] and in the asymmetric Biginelli reaction. [5] The hydrosilylation reaction is a widely employed method for accessing enantiomerically enriched amines, [6] and it is extremely useful from an industrial perspective, as it affords chiral products by using typically very cheap reducing agents.…”

Stereoselective metal-free catalytic synthesis of chiral trifluoromethyl aryl and alkyl amines

“…10 The reaction with trichlorosilane in the presence of catalytic amounts of a chiral Lewis base is a well-established. 11 In the last decade different classes of enantiomerically pure Lewis bases have been developed. 12 We started our investigation by screening different typologies of chiral activators, developed by us and other groups.…”

Mechanistic investigations of the asymmetric hydrosilylation of ketimines with trichlorosilane reveals a dual activation model and an organocatalyst with enhanced efficiency

“…Since the first chiral Lewis-base derived catalyst was reported in 2001, 1 there have been many variants of catalyst prepared and evaluated; 2,3 selected examples include formamides, [4][5][6][7] sulfinimides, 8,9 pyridines, [10][11][12] and organophosphorus compounds. [13][14][15] The main focus of research from this group has been using an imidazole derived catalyst that has been shown to function as efficiently as the reported analogous picolinoyl series, 16 in addition to being amenable to reductive amination protocols.…”