Selective Deuterium Incorporation into Azetidines and Cyclobutanes by Harnessing an Iodomethylthianthrenium Reagent

Deuterium incorporation at metabolically labile C-H bonds is an appealing strategy for improving metabolic stability and pharmacokinetic attributes in drug design campaigns. However, conventional H/D exchange methods often suffer from significant reactivity and selectivity challenges, limiting access to diverse deuterated structures. Here, we introduce a deuterium-labeled iodomethylthianthrenium reagent, readily prepared via H/D exchange with D2O, that directly converts alkenes into deuterated azetidines or cyclobutanes via a common 1,3-dielectrophilic intermediate. This method is compatible with a wide range of functional groups and is operationally simple, providing a reliable way to install deuterium at targeted positions in strained-ring scaffolds with high molecular complexity.