A Two-Step Synthesis of 2-Spiropiperidines

Abstract

A general two-step synthesis of 2-spiropiperidines has been developed. δ-Amino-β-ketoesters can be reacted with cyclic ketones to generate 2-spiropiperidines in good to excellent yields. The 2-spiropiperidines formed occupy an under-explored region of 3D-chemical space and are novel scaffolds for use in drug discovery programs. These 2-spiropiperidines can be further functionalised to generate small highly sp³ -rich structures, which exhibit an excellent likeness to lead-molecules in drug discovery.

Keywords: Maitland-Japp; medicinal chemistry; piperidine; scaffolds; spirocyclic.