Continuous-Flow Synthesis of Biaryls by Negishi Cross-Coupling of Fluoro- and Trifluoromethyl-Substituted (Hetero)arenes
Dr. Stefan Roesner
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139 USA
Search for more papers by this authorCorresponding Author
Prof. Dr. Stephen L. Buchwald
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139 USA
Search for more papers by this authorDr. Stefan Roesner
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139 USA
Search for more papers by this authorCorresponding Author
Prof. Dr. Stephen L. Buchwald
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139 USA
Search for more papers by this authorAbstract
A continuous-flow method for the regioselective arylation of fluoroarenes and fluoropyridines has been developed. The telescoped procedure reported here consists of a three-step metalation, zincation, and Negishi cross-coupling sequence, providing efficient access to a variety of functionalized 2-fluorobiaryl products. Precise temperature control of the metalation step, made possible by continuous-flow technology, allowed for the efficient preparation of the arylated products in high yields and short residence times. Additionally, several examples of the regioselective arylation of benzotrifluoride derivatives are also provided.
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