Efficient synthesis of novel 2-spiropiperidines including an unprecedented non-symmetrical 2,6-bis-spiropiperidine

Tertiary-alkyl substituted delta-amino-beta-ketoesters can be readily prepared from beta-amino acids, which can then undergo condensation with aldehydes to furnish novel, highly substituted 2-spiropiperidines. The method allows access to conformationally distinct structural- and regio-isomers of previously reported 2-spiropiperidines, and further expands the potential to explore three-dimensional chemical space. Using 3-oxetanone as the electrophile yielded the first example of a synthetically challenging non-symmetrical 2,6-bis-spiropiperidine. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

A series of highly substituted 2-spiropiperidines were synthesized using a new method, enriching the conformationally distinct structural- and regio-isomers of previously reported compounds and expanding the potential for exploring three-dimensional chemical space.