Kinetic Resolutions and Desymmetrisations

Abstract

This chapter deals with organocatalytic kinetic resolutions and desymmetrisations. The challenge of developing easily accessible and effective non-enzymatic asymmetric acylation catalysts has attracted many research groups over the last decade. In this context, the asymmetric acylation of alcohols using organocatalysts has emerged as a viable alternative to the well-established enzyme-catalysed acylation. In 2009, a highly enantioselective organocatalytic kinetic resolution of various secondary alcohols by using chirally modified 2-azaadamantane N-oxyls as organocatalysts was accomplished, providing excellent enantioselectivities when α-substituted cyclopentanols and cyclohexanols were employed as the substrates. On the other hand, the catalytic asymmetric desymmetrisation of meso anhydrides via the addition of an alcohol represents a simple and elegant method for the preparation of chiral hemiesters. In this context, the use of chiral amine catalysts has emerged as a powerful strategy for the enantioselective promotion of these reactions. For example, the use of a bifunctional thiourea-based cinchona alkaloid as a chiral organocatalyst in these reactions allowed the desymmetrisations of a wide range of meso anhydrides with excellent enantioselectivities by using an unprecedented catalyst loading of 1 mol %.