Enantioselective Palladium‐Catalyzed [3+2] Cycloaddition of Trimethylenemethane and Fluorinated Ketones |
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| Authors: | Prof. Dr. Barry M. Trost Dr. Guillaume Mata |
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| Affiliation: | Department of Chemistry, Stanford University, Stanford, CA, USA |
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| Abstract: | A nitrile‐substituted trimethylenemethane (TMM) donor undergoes palladium‐catalyzed [3+2] cycloadditions with fluorinated ketones to generate tetrasubstituted trifluoromethylated centers in high enantioselectivity under mild conditions. The generation of the palladium–TMM complex was achieved by a self‐deprotonation strategy, which shows remarkable improvements in regiocontrol, efficiency, and atom economy of asymmetric [3+2] cycloadditions. Moreover, the versatility of the nitrile group provides direct access to a variety of synthetically useful intermediates, including amides, aldehydes, and esters. The developed reaction conditions allow for the synthesis of a wide variety of aromatic, heteroaromatic, and aliphatic fluorinated dihydrofurans in excellent regio‐ and enantioselectivities. |
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| Keywords: | asymmetric catalysis cycloaddition dihydrofurans fluorine palladium |
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