Modern Catalytic Enantioselective Approaches to Piperidines

Abstract

Saturated heterocycles are very common motifs in numerous natural products and biologically active molecules. This chapter outlines various asymmetric approaches to piperidines. It focuses on catalytic, enantioselective methods that assemble piperidines from achiral or racemic building blocks. The chapter provides an overview of desymmetrization reactions, which proceed via the enantioselective addition of an electrophile or nucleophile to an achiral piperidine derivative, and dearomatization reactions, in which substituted pyridine derivatives serve as starting points for the synthesis of piperidines. It discusses multicomponent reactions, which merge two or more fragments in an enantioselective fashion to assemble a new ring, and annulation strategies, which rely on the asymmetric generation of a new stereocenter in a cyclization reaction. The cyclization of linear precursors via intramolecular N-alkylation, ring-closing metathesis, or lactam formation has become one of the most prominent methods for the synthesis of chiral piperidines.