Copper-catalysed radical amino-oxygenation of alkenes for the exclusive synthesis of 5-substituted 2-oxazolidinones

Abstract

Owing to the significance and difficulty in the precise construction of privileged drug-containing 5-substituted 2-oxazolidinones, we herein developed a copper-catalysed radical amino-oxygenation of alkenes with amine-derived tert-butyl chloro-carbamates. This newly developed method enables the one-step formation of C–N and C–O bonds and achieves a catalytic turnover under exogenous ligand- and base-free conditions. It offers a powerful alternative to existing methods for the exclusive synthesis of 5-substituted 2-oxazolidinones in 21–78% yields directly from abundant alkene feedstocks via an atom-economic procedure, featuring a broad substrate scope and functional group compatibility. The synthetic utility was further highlighted through the successful conversion of products to valuable β-amino alcohols, especially via the one-pot synthesis of a regioisomer of the cytokine modulator (±)-cytoxazone and a methylene derivative of epinephrine used in the pharmaceutical (±)-EpiPen®. Notably, the sustainability assessment by green metrics, such as the E-factor (2.9) and safety hazard scores (ES: 0.23/23.08 and SHS: 2.23/7.62), quantifies the obvious achievements of this protocol compared to precedents.