Open AccessControlling the Cleavage of Carbon–Carbon Bonds To Generate α,α-Difluorobenzyl Carbanions for the Construction of Difluoromethylbenzenes
Author(s) -
Hari Khatri,
Changho Han,
Erica Luong,
Xiaoliang Pan,
Amna T. Adam,
Maali D. Alshammari,
Yihan Shao,
David A. Colby
Publication year - 2019
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.9b01595
Subject(s) - carbanion , chemistry , reactivity (psychology) , reagent , potassium carbonate , cleavage (geology) , carbonate , fragmentation (computing) , carbon fibers , combinatorial chemistry , organic chemistry , medicine , materials science , alternative medicine , geotechnical engineering , pathology , fracture (geology) , composite number , computer science , engineering , composite material , operating system
Controlling the cleavage of carbon-carbon bonds during a chemical reaction is a substantial challenge; however, synthetic methods that accomplish this objective produce valuable and often unexplored reactivity. We have designed a mild process to generate α,α-difluorobenzyl carbanions in the presence of potassium carbonate by exploiting the cleavage of C-C bonds during the release of trifluoroacetate. The initiating reagent is potassium carbonate, which represents an improvement over existing protocols that require a strong base. Fragmentation studies across substituted arenes and heteroarenes were conducted along with computational analyses to elucidate reactivity trends. Furthermore, the mildly generated α,α-difluorobenzyl carbanions from electron-deficient aromatics and heteroaromatic rings can react with aldehydes to create derivatives of difluoromethylbenzenes, which are valuable synthetic targets.