Asymmetric tandem aldol-cyclyzation with ethyltrifluoropyruvate catalyzed by Cinchona alkaloid/Lewis acid combination

ORGN 647

Shinichi Ogawa, 17515004@stn.nitech.ac.jp1, Norihito Iida1, Yudong Yang1, Shuichi Nakamura2, Norio Shibata, nozshiba@nitech.ac.jp2, 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
Compounds which contain trifluoromethyl group show unique properties due to fluorine atoms, in particular, trifluoromethylated heterocycles have great consequence, because of their contribution of agricultural and medicinal chemistry. Therefore, a simple and flexible method which construct trifluoromethylated heterocyclic system has been necessary. In terms of this demands, we recently have reported efficient synthesis of bicyclic -α-hydroxy-α-trifluoromethyl-γ-lactams through an aldol-type cyclization reaction of variety of enamines with ethyl 3,3,3-trifluoropyruvate either base catalysis or without. Then we tried to examine an asymmetric version of this reaction and found that the reaction was effectively catalyzed by cinchona alkaloids to give aldol-type cyclization products in high yields with good ees. After further investigation, a cinchona alkaloids/Lewis acids combination system was found to be effective for this transformation and gave desirable α-hydroxy-α-trifluoromethyl-γ-lactams with high enantioselectivities. In this presentation, we are going to discuss in details.