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

• Published in: Nature communications Vol. 7; no. 1; pp. 12901 - 9
• Main Authors: Liao, Gang, Yin, Xue-Song, Chen, Kai, Zhang, Qi, Zhang, Shuo-Qing, Shi, Bing-Feng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.09.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/933; 639/638/549/933; 639/638/77/888; Carbon monoxide; Catalysis; Humanities and Social Sciences; Ligands; multidisciplinary; Science; Science (multidisciplinary); United States > US; California
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms12901

Several examples on Pd-catalysed carbonylation of methyl C( sp 3 )–H bonds with gaseous CO via Pd(II)/Pd(0) catalysis have been reported. However, methylene C( sp 3 )–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( sp 3 )–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. Carbonylation of unactivated C-H bonds is typically carried out on primary C-H sites using gaseous carbon monoxide. Here the authors report a palladium cataylsed alkoxycarbonylation process using alkyl chloroformates that functionalises more challenging unactivated secondary C-H sites.