Divergent chemical synthesis of prolines bearing fluorinated one-carbon units at the 4-position via nucleophilic 5-endo-trig cyclizations

作者：Nadano Ryo; Iwai Yu; Mori Takashi; Ichikawa Junji^*

来源：Journal of Organic Chemistry, 2006, 71(23): 8748-8754.

DOI：10.1021/jo061421n

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(N)2'-type reaction in the normally disfavored 5-endo-trig fashion, leading to 2-substituted 4-(trifluoromethyl)- or 4-(difluoromethylene)pyrrolidines. Both alpha- and beta-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.

• 出版日期2006-11-10