Asymmetric Synthesis of Efavirenz via Organocatalyzed Enantioselective Trifluoromethylation

作者：Okusu Satoshi; Kawai Hiroyuki; Yasuda Yoshimasa; Sugita Yutaka; Kitayama Takashi; Tokunaga Etsuko; Shibata Norio^*

来源：Asian Journal of Organic Chemistry, 2014, 3(4): 449-452.

DOI：10.1002/ajoc.201402016

• cinchona alkaloids
• efavirenz
• organocatalysis
• tetramethylammonium fluoride
• trifluoromethylation

We demonstrate a metal-free catalytic process for the synthesis of anti-HIV drug efavirenz in 99% ee, which was achieved by an organocatalyzed enantioselective trifluoromethylation with Me3SiCF3 as a key reaction. The combination of cinchona alkaloid-derived phase-transfer catalysts modified with long chain ethers and tetramethylammonium fluoride enables the enantioselective trifluoromethylation of 1-(5-chloro-2-nitrophenyl)-3-cyclopropylprop-2-yn-1-one to be improved, and provides a desired (S)-trifluoromethyl carbinol, which is a two-step key precursor for the synthesis of efavirenz, in up to 80% ee. As our method is a metal-free process, it would provide an alternative industrial manufacturing process for efavirenz.

• 出版日期2014-4