The Oxidative Trifluoromethylthiolation Of Unsaturated Carboxylic Acids With AgSCF₃

The incorporation of a SCF₃ moiety into organic molecules can improve the physical,chemical,and biological properties of parent compounds.The unsaturated carboxylic acids includingα,β-unsaturated carboxylic acids,2,3-allenoic acids and propiolic acid derivatives are fundamentally important compounds.This dissertation is focused on the development of metal-mediated/catalyzed oxidative cross-coupling reactions between the trifluoromethylthiolating reagent（AgSCF₃）and various unsaturated carboxylic acids（α,β-unsaturated carboxylic acids,2,3-allenoic acids and propiolic acids）.The major research work includes the following contents.1.An efficient copper-mediated decarboxylative trifluoromethylthiolation ofα,β-unsaturated carboxylic acids with AgSCF₃ has been developed.A variety of aryl substitutedα,β-unsaturated carboxylic acids were effective,and cinnamic acid with an alkyl substitution at ortho-,meta-or para-position were transferred into corresponding products in good to excellent yields and E/Z selectivities.A variety of functional groups such as halogen,naphthyl and heteroaryl were tolerated under the reaction conditions.This reaction provides a general,straightforward and practically useful method for preparing vinyl trifluoromethyl thioethers.2.A tunable decarboxylative trifluoromethylthiolation ofα,β-unsaturated carboxylic acids with AgSCF₃ was developed to affordα-SCF₃-substituted ketones by using iron-mediated condition.This novel method has demonstrated mild reaction condition,broad substrate scope and excellent functional-group tolerance.This oxidative trifluoromethylthiolation provides a novel synthetic strategy ofα-SCF₃-substituted ketones.3.The oxidative trifluoromethylthiolation of 2,3-allenoic acids with AgSCF₃ in the presence of（NH₄）₂S₂O₈ and copper salt was investigated.A series of 4-aryl-2,3-allenoic acids underwent radical trifluoromethylthiolation/intramolecular cyclization to affordβ-trifluoromethythiolated butenolides,which can be conveniently transfered into trifluoromethythiolated furan derivatives.In contrast,2-unsubstituted 2,3-allenoic acids were converted into corresponding 3,4-bis（trifluoromethylthio）but-2-enoic-acids under the similar reaction conditions.4.A copper-catalyzed chemo-and stereoselective oxidative bis-trifluoromethylthiolation of propiolic acid derivatives was achieved by using carboxylic group as the activating group and formic acid as a co-solvent.The reaction of propiolic acid derivatives and AgSCF₃ in the presence of catalytic Cu（OAc）₂ in MeCN/HCO₂H afforded bis-trifluoromethylthiolated acrylic acids in moderate to excellent yields with E selectivity.Further derivatization of the resultant products gave a series of polysubstituted SCF₃-containing alkenes.