Mechanism and Origins of Stereoinduction in Natural Cinchona Alkaloid Catalyzed Asymmetric Electrophilic Trifluoromethylthiolation of β-Keto Esters with N-Trifluoromethylthiophthalimide as Electrophilic SCF3 Source

摘要: The trifluoromethylthio (SCF3) group enjoys a privileged role in the field of drug discovery because its incorporation into molecule often leads to significantly improved pharmacokinetics and efficacy. In spite prime importance discovery, stereospecific introduction SCF3 target molecules has remained an unmet challenge. A major breakthrough was made 2013 when Rueping Shen simultaneously independently disclosed natural Cinchona alkaloid catalyzed asymmetric electrophilic trifluoromethylthiolation β-keto esters. However, two key issues remain obscure. (a) What is preferred mode catalysis? (b) How induction accomplished? Here we report in-depth computational exploration mechanism origin stereoinduction esters with N-trifluoromethylthiophthalimide as source. Three mechanistic possibilities, i.e., transfer-trifluoromethyl...