Difluoroalkylation of Tertiary Amides and Lactams by an Iridium-Catalyzed Reductive Reformatsky Reaction

Overview

Journal Org Lett

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2022 Mar 8

PMID 35258311

Authors

Phillip Biallas

Ken Yamazaki

Darren J Dixon

Affiliations

Soon will be listed here.

Abstract

An iridium-catalyzed, reductive alkylation of abundant tertiary lactams and amides using 1-2 mol % of Vaska's complex (IrCl(CO)(PPh)), tetramethyldisiloxane (TMDS), and difluoro-Reformatsky reagents (BrZnCFR) for the general synthesis of medicinally relevant α-difluoroalkylated tertiary amines is described. A broad scope (46 examples), including -aryl- and -heteroaryl-substituted lactams, demonstrated an excellent functional group tolerance. Furthermore, late-stage drug functionalizations, a gram-scale synthesis, and common downstream transformations proved the potential synthetic relevance of this new methodology.

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