Iron-Catalyzed Asymmetric Haloazidation of α,β-Unsaturated Ketones: Construction of Organic Azides with Two Vicinal Stereocenters

Journal of the American Chemical Society

4 years ago

Iron-Catalyzed Asymmetric Haloazidation of α,β-Unsaturated Ketones: Construction of Organic Azides with Two Vicinal Stereocenters

Lili Lin, Pengfei Zhou, Xiaohua Liu, Xia Zhong, Xiaoming Feng, Long Chen

Organic azides play important roles in synthetic chemistry, chemical biology, drug discovery, and material science. Azido-functionalization of alkenes is one of the most efficient procedures for rapid introduction of azide group into organic compounds. But only a few examples have been documented in the catalytic asymmetric version of the azidation of alkenes. Herein, we report an unprecedented highly diastereo- and enantioselective bromoazidation of α,β-unsaturated ketones catalyzed by chiral N,N′-dioxide/Fe(OTf)₂ complexes. An array of aryl, heteroaryl, and alkyl substituted α,β-unsaturated ketones were transformed to the corresponding α-bromo-β-azido ketones in high yields with excellent diastereo- and enantioselectivities. The catalytic system was also applicable for chloroazidation and iodoazidation of chalcone. Kinetic studies and some control experiments suggested that the reaction might proceed via a 1,4-addition/halogenation pathway.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b06029

DOI: 10.1021/jacs.7b06029