Nucleophilic Additions to CN Double Bonds

Abstract

This chapter deals with enantioselective nucleophilic additions to C=O double bonds, such as Mannich reactions, aza-Henry reactions, aza-Morita-Baylis-Hillman reactions, and Strecker reactions. Among a wide variety of chiral organocatalysts that have been used in the asymmetric Mannich reaction, one of the most widely used remains proline itself, which generally provided excellent enantioselectivities for the Mannich products arisen from either three-component one-pot reactions or reactions of preformed imines with aldol donors. Various chiral amine-thioureas have also been successfully applied to efficiently promote various other Mannich reactions. There are still only few organocatalytic asymmetric aza-Henry reactions reported which can afford both an excellent enantioselectivity and a high anti-selectivity for a broad scope of the reaction partners. In the last year, several chiral bifunctional thiourea catalysts were studied as potential organocatalysts. Among them, a bifunctional thiourea-secondary amine derived from trans-cyclohexane diamine was shown to efficiently promote the aza-Henry reaction of N-Boc imines with nitroalkanes, providing excellent enantioselectivities and high anti-selectivities. Several interesting results dealing with the enantioselective organocatalytic aza- Morita−Baylis−Hillman reaction have been reported, such as those concerning the reactions of aromatic imines with β-naphthyl acrylate, providing uniformly excellent enantioselectivities. In the area of the enantioselective Strecker reaction, a novel N,N'-dioxide catalyst derived from BINOL and prolinamide was successfully applied as organocatalyst to the Strecker reaction of ketoimines, providing excellent enantioselectivities. A chiral thiourea catalyst was used to develop the first organocatalytic asymmetric three-component Strecker reaction with excellent enantioselectivities.