C-N and C-O Bond Formation in Copper-Catalyzed/Mediated sp3 C-H Activation: Mechanistic Studies from Experimental and Computational Aspects

Yuhang Yang; Fei Cao; Linbin Yao; Tao Shi; Bencan Tang; Yoichiro Kuninobu; Zhen Wang

doi:10.1021/acs.joc.0c01038

C-N and C-O Bond Formation in Copper-Catalyzed/Mediated sp³ C-H Activation: Mechanistic Studies from Experimental and Computational Aspects

J Org Chem. 2020 Aug 7;85(15):9713-9726. doi: 10.1021/acs.joc.0c01038. Epub 2020 Jul 29.

Authors

Yuhang Yang¹, Fei Cao², Linbin Yao³, Tao Shi¹, Bencan Tang³, Yoichiro Kuninobu⁴, Zhen Wang^{1

2}

Affiliations

¹ School of Pharmacy, Lanzhou University, West Donggang Road No. 199, Lanzhou 730000, Gansu, China.
² State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, Gansu, China.
³ Department of Chemical and Environmental Engineering, Faculty of Science and Engineering, The University of Nottingham Ningbo China, 199 Taikang East Road, Ningbo 315100, China.
⁴ Institute for Materials Chemistry and Engineering, Kyushu University, 6-1 Kasugakoen, Kasuga-shi, Fukuoka 816-8580, Japan.

PMID: 32678601
DOI: 10.1021/acs.joc.0c01038

Abstract

Mechanistic studies on Cu-catalyzed/mediated sp³ C-H amidation and acetoxylation are investigated from experimental and computational aspects. The concerted metalation-deprotonation (CMD) mechanism rather than a radical-involved pathway is proved to occur in amidation and acetoxylation reactions, and this is the rare example of the CMD mechanism involved in the more challenging sp³ C-H activations. Theoretical calculations demonstrated that CMD is the rate-determining step either for methylic or benzylic positions in amidation and acetoxylation reactions, and intermolecular nucleophilic addition of acetate anions is more favorable than the ring opening of β-lactams and intramolecular acetoxylation. These mechanistic studies on the divergent and condition-dependent product formation are critical for developing Cu-promoted C-H functionalization via the CMD mechanism.