syn-Selective Construction of Fused Heterocycles by Catalytic Reductive Tandem Functionalization of N-Heteroarenes

Authors：Yang, Jian; Zhao, He; Tan, Zhenda; Cao, Liang; Jiang, Huanfeng; Ci, Chenggang^*; Dixneuf, Pierre H.; Zhang, Min^*

Source：ACS Catalysis, 2021, 11(15): 9271-9278.

DOI：10.1021/acscatal.1c01328

• diastereoselectivity
• ruthenium catalysis
• reductive dearomatization
• tandem functionalization
• N-heteroarenes

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 C-3-benzylation and hydroxymethylation followed by C-2-aryloxylation of N-heteroarenium salts, proceeding with broad substrate scope, good functional group tolerance, high atom efficiency, and applicability for postfunctionalization of some biomedical molecules.