Open AccessA Difluoromethylene Linchpin/Synthon: Application in Conjunction with Anion Relay Chemistry (ARC) Permits Ready Access to Diverse Difluoromethylene Scaffolds
Author(s) -
Kevin T. O’Brien,
Jonathan W. Nadraws,
Amos B. Smith
Publication year - 2020
Publication title -
organic letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.94
H-Index - 239
eISSN - 1523-7060
pISSN - 1523-7052
DOI - 10.1021/acs.orglett.0c03508
Subject(s) - synthon , chemistry , carbanion , reagent , component (thermodynamics) , adduct , electrophile , combinatorial chemistry , alkoxide , aldehyde , silylation , organic chemistry , catalysis , physics , thermodynamics
Organodifluorine synthons, in conjuction with three-component diastereoselective anion relay chemistry (ARC), permit ready access to diverse difluoromethylene scaffolds. Initiated via [1,2]-addition of an organolithium reagent to a β-difluoromethylene silyl aldehyde, an alkoxide intermediate is formed, which is capable of undergoing a [1,4]-Brook rearrangement to generate a stabilized α-difluoromethylene carbanion, which, upon electrophile capture, affords a three-component adduct. This three component synthetic tactic represents a novel one-pot divergent strategy for the construction of diverse organodifluorine containing compounds.