Novel chiral crown ethers catalyze nucleophilic enantioselective trifluoromethylation of carbonyls

ORGN 736

Hiroyuki Kawai,, Akihiro Kusuda2, Shuichi Nakamura2, Norio Shibata,, and Takeshi Toru2. (1) Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, 19-628, Gokiso, Showa, Nagoya, 466-8555, Japan, (2) Department of Frontier Materials, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya, 466-8555, Japan
Trifluoromethyl-containing organic compounds have attracted much attention because of their application in the field of medicinal and agrochemical chemistry. Among a variety of approaches available for the synthesis of the α-trifluoromethyl alcohols, enantioselective nucleophilic trifluoromethylation of carbonyl compounds using the Ruppert-Prakash reagent, (trifluoromethyl)trimethylsilane, Me3SiCF3, is surely the most straightforward operation for construction of the corresponding chiral molecules. Recently, we disclosed the highly enantioselective trifluoromethylation of aryl ketones with Me3SiCF3 catalyzed by a combination of ammonium bromides derived from cinchona alkaloids and tetramethylammonium fluoride (TMAF). However this method was not effective for the enantioselective trifluoromethylation of aldehydes, and all of the previous reports for enantioselective trifluoromethylation including our results, phase-transfer catalysts have been used. We attempt herein the enantioselective trifluoromethylation of carbonyl compounds by the use of chiral crown ethers.