Divergent Chemical Synthesis of Prolines Bearing Fluorinated One-Carbon Units at the 4-Position via Nucleophilic 5-Endo-Trig Cyclizations

J. Org. Chem., 71 (23), 8748 -8754, 2006. 10.1021/jo061421n S0022-3263(06)01421-6
Web Release Date: October 18, 2006

Divergent Chemical Synthesis of Prolines Bearing Fluorinated One-Carbon Units at the 4-Position via Nucleophilic 5-Endo-Trig Cyclizations

Ryo Nadano, Yu Iwai, Takashi Mori, and Junji Ichikawa*

Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

junji@chem.s.u-tokyo.ac.jp

Received July 8, 2006

Abstract:

N-[3-(Trifluoromethyl)homoallyl]sulfonamides, prepared via ring opening of (S)-glycidyl ethers or 2-aryloxiranes with 1-(trifluoromethyl)vinyllithium, underwent intramolecular addition or S_N2'-type reaction in the normally disfavored 5-endo-trig fashion, leading to 2-substituted 4-(trifluoromethyl)- or 4-(difluoromethylene)pyrrolidines. Both

- and

-face-selective hydrogenation of the 4-difluoromethylene group afforded syn- and anti-4-(difluoromethyl)pyrrolidines, respectively. These sequences, followed by the oxidation of a 2-hydroxymethyl or 2-aryl group, successfully provided prolines with a trifluoromethyl, difluoromethylene, or difluoromethyl group at the 4-position, including optically active prolines.

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