Deuteriodifluoromethylation and <i>gem</i>‐Difluoroalkenylation of Aldehydes Using ClCF<sub>2</sub>H in Continuous Flow
Wai Chung Fu, Timothy F. Jamison
Abstract
Abstract The deuteriodifluoromethyl group (CF 2 D) represents a challenging functional group due to difficult deuterium incorporation and unavailability of precursor reagents. Herein, we report the use of chlorodifluoromethane (ClCF 2 H) gas in the continuous flow deuteriodifluoromethylation and gem ‐difluoroalkenylation of aldehydes. Mechanistic studies revealed that the difluorinated oxaphosphetane (OPA) intermediate can proceed via alkaline hydrolysis in the presence of D 2 O to provide α‐deuteriodifluoromethylated benzyl alcohols or undergo a retro [2+2] cycloaddition under thermal conditions to provide the gem ‐difluoroalkenylated product.
Topics & Concepts
UnavailabilityCycloadditionReagentChemistryHydrolysisContinuous flowDeuteriumFunctional groupOrganic chemistryMedicinal chemistryCombinatorial chemistryCatalysisMathematicsPhysicsPolymerMechanicsQuantum mechanicsStatisticsFluorine in Organic ChemistryChemical Reactions and IsotopesInorganic Fluorides and Related Compounds