A nickel-catalyzed
carbonylative difluoroalkylation reaction with
arylboronic acids under 1 atm of CO has been developed. The reaction
proceeds under mild reaction conditions with high efficiency and high
functional group tolerance. Preliminary mechanistic studies reveal
that the arylacyl nickel complex is the key intermediate to circumvent
the formation of labile fluoroacyl nickel, and bimetallic oxidative
addition is likely the key step to facilitate the catalytic cycle.
Cite this: CCS Chem. 2020, 2, 293-304Difluoromethylated alkynes are a versatile synthon for the diversity-oriented synthesis of difluoromethyl compounds that are of great interest in life and materials sciences. However, the catalytic cross-coupling for the synthesis of difluoromethylated alkynes remains challenging, despite impressive achievements made in the cross-coupling reactions for alkynes, including the Sonogashira reaction. Here, we report a palladium difluorocarbene involvement in catalytic coupling with terminal alkynes, representing a new mode of conjugation reaction, which circumvents the radical pathway usually encountered during the coupling of alkynes with fluoroalkyl electrophiles. The reaction uses inexpensive and abundant industrial raw material chlorodifluoromethane (ClCF 2 H) as the difluorocarbene precursor, and features cost-effectiveness, excellent functional group tolerance, and broad substrate scope, including synthesis of drug-like complex molecules. Our mechanistic studies showed a unique catalytic pathway of this process, in which additive hydroquinone plays a pivotal role in promoting the reaction. + [Pd] (2.5 mol %) Xantphos (2.5 or 7.5 mol %) Hydroquinone, K 2 CO 3 dioxane/DMA (w/wo), 80 o C CF 2 H R Het R Het [Pd 0 ]=CF 2 via cat. [Pd] nucleophilic 32 examples, yield up to 95% alkyne hydroquinone hydroquinone F F Cl H RESEARCH ARTICLE
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.