Controlling the Cleavage of Carbon–Carbon Bonds To Generate α,α-Difluorobenzyl Carbanions for the Construction of Difluoromethylbenzenes
- Hari R. KhatriHari R. KhatriDepartment of BioMolecular Sciences, University of Mississippi, University, Mississippi 38677, United StatesMore by Hari R. Khatri
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- Changho HanChangho HanDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, United StatesMore by Changho Han
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- Erica LuongErica LuongDepartment of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United StatesMore by Erica Luong
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- Xiaoliang PanXiaoliang PanDepartment of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United StatesMore by Xiaoliang Pan
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- Amna T. AdamAmna T. AdamDepartment of BioMolecular Sciences, University of Mississippi, University, Mississippi 38677, United StatesMore by Amna T. Adam
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- Maali D. AlshammariMaali D. AlshammariDepartment of BioMolecular Sciences, University of Mississippi, University, Mississippi 38677, United StatesMore by Maali D. Alshammari
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- Yihan ShaoYihan ShaoDepartment of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019, United StatesMore by Yihan Shao
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- David A. Colby*David A. Colby*E-mail: [email protected]Department of BioMolecular Sciences, University of Mississippi, University, Mississippi 38677, United StatesMore by David A. Colby
Abstract
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.
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