Stereoselective alkoxycarbonylation of unactivated C(sp3)-H bonds with alkyl chloroformates via Pd(II)/Pd(IV) catalysis

Gang Liao; Xue-Song Yin; Kai Chen; Qi Zhang; Shuo-Qing Zhang; Bing-Feng Shi

doi:10.1038/ncomms12901

Stereoselective alkoxycarbonylation of unactivated C(sp3)-H bonds with alkyl chloroformates via Pd(II)/Pd(IV) catalysis

Nat Commun. 2016 Sep 28:7:12901. doi: 10.1038/ncomms12901.

Authors

Gang Liao¹, Xue-Song Yin¹, Kai Chen², Qi Zhang¹, Shuo-Qing Zhang¹, Bing-Feng Shi¹

Affiliations

¹ Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
² Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.

Abstract

Several examples on Pd-catalysed carbonylation of methyl C(sp³)-H bonds with gaseous CO via Pd(II)/Pd(0) catalysis have been reported. However, methylene C(sp³)-H carbonylation remains a great challenge, largely due to the lack of reactivity of C-H bonds and the difficulty in CO migratory insertion. Herein, we report the stereoselective alkoxycarbonylation of both methyl and methylene C(sp³)-H bonds with alkyl chloroformates through a Pd(II)/Pd(IV) catalytic cycle. A broad range of aliphatic carboxamides and alkyl chloroformates are compatible with this protocol. In addition, this process is scalable and the directing group could be easily removed under mild conditions with complete retention of configuration.