Divergent chemical synthesis of prolines bearing fluorinated one-carbon units at the 4-position via nucleophilic 5-endo-trig cyclizations.
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.
Nadano
Ryo
R
Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Tokyo 113-0033, Japan.
Iwai
Yu
Y
Mori
Takashi
T
Ichikawa
Junji
J
D002244:Carbon / Q000737:chemistry*; D003500:Cyclization; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
D006845:Hydrocarbons, Fluorinated; D013449:Sulfonamides; D002244:Carbon; D011392:Proline