Diastereoselective Synthesis of N-Heterocycle Substituted Cyclobutanes via Michael Addition onto Cyclobutenes

Chemistry. 2024 Nov 25:e202403986. doi: 10.1002/chem.202403986. Online ahead of print.

Abstract

Herein, we present a method for the diastereoselective synthesis of N-heterocycle-substituted cyclobutanes from commercially available bromocyclobutanes. This method enables the efficient formation of various heterocyclic aminocyclobutane esters and amides using simple reagents. Notably, N-nucleophiles such as imidazoles, azoles, and nucleobase derivatives were successfully incorporated, enhancing the chemical diversity of small ring building blocks for medicinal chemistry applications.

Keywords: Cyclobutanes; Cyclobutenes; Diastereoselectivity; Michael addition; Small ring systems.