syn-Selective Construction of Fused Heterocycles by Catalytic Reductive Tandem Functionalization of N-Heteroarenes
Jian Yang, He Zhao, Zhenda Tan, Liang Cao, Huanfeng Jiang, Chenggang Ci,* Pierre. H. Dixneuf, Min Zhang*
ABSTRACT: To date, numerous methods have been successfully developed to functionalize N-heteroaryl C-H bonds. In contrast, dearomative tandem functionalization of N-heteroarenes is still a subject to be explored. Reported herein is an example on reductive dearomatization-induced tandem functionalization of N-heteroarenes by ruthenium catalysis, which offers a general method for diastereoselective construction of fused heterocycles featuring a cyclic syn-N, O-acetal motif from N-heteroarenes, phenols, and paraformaldehyde. Mechanistic study reveals that the products are formed via a tandem sequence of pyridyl C3-benzylation and hydroxymethylation followed by C2-aryloxylation of N-heteroarenium salts, proceeding with broad substrate scope, good functional group tolerance, high atom-efficiency, and applicability for post-functionalization of some biomedical molecules.
ACS Catal. 2021, 11, 9271-9278.