Iridium-Catalyzed anti-Diastereo- and Enantioselective Garbonyl (α-Trifluoromethyl)alrylation from the Alcohol or Aldehyde Oxidation Level

摘要

It is estimated that 20 of approved pharmaceutical agents and 3CM10 of commercially available agrochemicals contain one or more fluorine atoms. Additionally, in 2006, 80 of the small-molecule drugs entering the market were estimated to contain one or more chiral centers. These facts underscore the importance of developing enantioselective methods for the preparation of organofluorine compounds.Toward this end, highly enantioselective micleophilic trifluoromethy-lations of aldehydes and ketones have been developed. Nucleophilic (α-trifluoromethyl)allylation might also serve to establish absolute stereochemistry at CF3-bearing carbon centers. Yet, despite persistent efforts aimed at the development of asymmetric carbonyl allylation protocols, enantioselective carbonyl (α-trifluoromethyl)allylation remains an unmet challenge. Here, under the conditions of C—C bond forming transfer hydrogenation,A we report the first examples of enantioselective carbonyl α-trifluoromethyl)allylation: a process in which carbonyl addition occurs with equal facility from the alcohol or aldehyde oxidation level.