Iron-Catalyzed Enantioselective Radical Carboazidation and Diazidation of α,β-Unsaturated Carbonyl Compounds

Azidation of alkenes is an efficient protocol to synthesize organic azides which are important structural motifs in organic synthesis. Enantioselective radical azidation, as a useful strategy to install a C-N-3 bond, remains challenging due to the inherently instability and unique structure of radicals. Here, we disclose an efficient enantioselective radical carboazidation and diazidation of alpha,beta-unsaturated ketones and amides catalyzed by chiral N,N'-dioxide/Fe(OTf)(2) complexes. An array of substituted alkenes was transformed to the corresponding alpha-azido carbonyl derivatives in good to excellent enantioselectivities, benefiting the preparation of chiral alpha-amino ketones, vicinal amino alcohols, and vicinal diamines. Control experiments and mechanistic studies proved the radical pathway in the reaction process. The DFT calculations showed that the azido transferred to the radical intermediate via an intramolecular five-membered transition state with the internal nitrogen of the Fe-N-3 species.

Automated summary

This study presents an efficient enantioselective radical carboazidation and diazidation reaction of α,β-unsaturated ketones and amides catalyzed by chiral N,N'-dioxide/Fe(OTf)(2) complexes, enabling the preparation of chiral compounds from substituted alkenes. Control experiments and mechanistic studies confirmed the radical pathway in the reaction process.