Diastereoselective [3 + 2] Cycloaddition between Tertiary Amine N-Oxides and Substituted Alkenes to Access 7-Azanorbornanes

Org Lett. 2024 Aug 9;26(31):6546-6550. doi: 10.1021/acs.orglett.4c02013. Epub 2024 Jul 22.

Abstract

We have developed a diastereoselective synthesis of 43 novel 7-azanorbornanes using tertiary amine N-oxides and substituted alkenes. Our method uses an efficient [3 + 2] cycloaddition, starting from either commercially available or easily accessible precursors to generate yields up to 97% and diastereomeric ratios up to >20:1. Density functional theory (DFT) calculations were performed, suggesting that the observed diastereoselectivity is likely due to steric considerations.