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
J. Org. Chem., 2006, 71 (23), pp 8748–8754
DOI: 10.1021/jo061421n
Publication Date (Web): October 18, 2006
Copyright © 2006 American Chemical Society
*

 To whom correspondence should be addressed. Tel/Fax:  +81-3-5841-4345.

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

Abstract

Abstract Image

N-[3-(Trifluoromethyl)homoallyl]sulfonamides, prepared via ring opening of (S)-glycidyl ethers or 2-aryloxiranes with 1-(trifluoromethyl)vinyllithium, underwent intramolecular addition or SN2‘-type reaction in the normally disfavored 5-endo-trig fashion, leading to 2-substituted 4-(trifluoromethyl)- or 4-(difluoromethylene)pyrrolidines. Both α- and β-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.

View: Full Text HTML | Hi-Res PDF

Tools

History

  • Published In Issue November 10, 2006
  • Received July 8, 2006

Recommend & Share

Related Content

Other ACS content by these authors: