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

[Image: see text] An iridium-catalyzed, reductive alkylation of abundant tertiary lactams and amides using 1–2 mol % of Vaska’s complex (IrCl(CO)(PPh(3))(2)), tetramethyldisiloxane (TMDS), and difluoro-Reformatsky reagents (BrZnCF(2)R) for the general synthesis of medicinally relevant α-difluoroalky...

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Detalles Bibliográficos
Autores principales: Biallas, Phillip, Yamazaki, Ken, Dixon, Darren J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082613/
https://www.ncbi.nlm.nih.gov/pubmed/35258311
http://dx.doi.org/10.1021/acs.orglett.2c00438
Descripción
Sumario:[Image: see text] An iridium-catalyzed, reductive alkylation of abundant tertiary lactams and amides using 1–2 mol % of Vaska’s complex (IrCl(CO)(PPh(3))(2)), tetramethyldisiloxane (TMDS), and difluoro-Reformatsky reagents (BrZnCF(2)R) for the general synthesis of medicinally relevant α-difluoroalkylated tertiary amines is described. A broad scope (46 examples), including N-aryl- and N-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.