Recent Advances in Synthesis of Enantioenriched 2‐Substituted Piperidine Derivatives

Abstract Enantioenriched 2‐substituted piperidines are very important unit for drug discovery. Ready access to a wide range of such compounds, decorated with functional handles at 2‐position with stereo‐defined centre significantly enhance the quality and diversity of chemical libraries for screening of drug discovery. The ability to control the stereochemistry of piperidine at the 2‐position remains an area of interest in organic synthesis to allow the development of novel, structurally diverse 3D molecules. Among the various ways to obtain enantioenriched 2‐substituted piperidines, asymmetric hydrogenation is widely studied. Asymmetric synthesis, Kinetic resolution, and chiral pool synthesis methodologies are also important ways to obtain the enantioenriched 2‐substituted piperidines. This review article summarized the main four ways to achieve particularly the enantioenriched substituted piperidines only at 2‐position considering the chemical routes, excluding the biocatalytic approach. 1. Introduction 2.1 Asymmetric Hydrogenation of 2‐substituted Pyridines 2.2 Asymmetric Synthesis 2.3. Kinetic resolution of racemic 2‐substituted Piperidine derivatives 2.4. Chiral pool synthesis 3. Conclusions & outlook