Improved synthesis and application of planar-chiral nucleophilic catalysts in asymmetric reactions and copper-catalyzed enantioselective N-H insertion reactions

Abstract

The development of an improved synthesis of nucleophilic planar-chiral catalysts is described in Chapter 1. This route is amenable to scale-up and preparative chiral HPLC is unnecessary to resolve the racemic catalysts. Using planar-chiral catalysts, two synthetic methodology projects have been developed: Chapter 2 describes the first asymmetric synthesis of trans P-lactams, and Chapter 3 describes the asymmetric synthesis of tertiary a-chloroesters. In the chapter describing the asymmetric synthesis of trans [beta]-lactams, we present mechanistic data supporting a novel mechanism, in which the N-triflylimine, rather than the ketene, reacts with the catalyst first. In the chapter describing the asymmetric synthesis of tertiary a-chloroesters, we introduced an under-utilized commercially available chlorinating reagent (2,2,6,6-tetrachlorocyclohexanone). Finally, in chapter 4, the Cu-catalyzed asymmetric synthesis of [alpha]-aminoesters via an N-H insertion is described. We have demonstrated that carbamates such as BocNH2 and CbzNH2 are efficient coupling partners in reactions with a-diazoesters to generate highly useful Boc- or Cbz-protected a-aminoesters.