Synthesis of Chiral <i>gem</i>-Difluoromethylene Compounds by Enantioselective Ethoxycarbonyldifluoromethylation of MBH Fluorides via Silicon-Assisted C–F Bond Activation
Yuji Sumii, T. Nagasaka, Jiandong Wang, Hiroto Uno, Norio Shibata
Abstract
The enantioselective ethoxycarbonyldifluoromethylation of Morita–Baylis–Hillman (MBH) fluorides with Me3SiCF2CO2Et under organocatalysis is described. Moderately functionalized chiral gem-difluoromethylene compounds with a stereogenic “C-CF2-C*” unit were synthesized in high yields with high enantioselectivities. The initial C–F bond activation is assisted by the silicon atom via a dual SN2′-SN2′ stepwise pathway. Dynamic kinetic resolution of the MBH-fluorides explained the high yields and high ee’s of the products. The method was extended to the enantioselective introduction of “Het-CF2” units.
Topics & Concepts
ChemistryEnantioselective synthesisSiliconCombinatorial chemistryOrganic chemistryMedicinal chemistryComputational chemistryStereochemistryCatalysisFluorine in Organic ChemistryInorganic Fluorides and Related Compounds