4-Difluoromethylene-1-Pyrrolines by Intramolecular Heck Cyclization

Abstract

A mechanistically interesting construction of fluoropyrrolines is reported. In the suggested mechanism, the oxidative addition product of Pd(0) insertion into the N-O bond of 2-(trifluoromethyl)allyl ketone O-pentafluorobenzoyloximes undergoes 5-endo-trig Heck cyclization (unfavorable by Baldwin’s rules) to give an α-trifluoromethyl Pd species that undergoes β-fluo­ride elimination to yield 4-difluoromethylene-1-pyrrolidines in poor to good yields. The unfavorable cyclization is overcome by the known β-arylation selectivity of trifluoromethyl groups in Heck reactions as rationalized by DFT calculations (R. J. Deeth, A. Smith, J. M. Brown J. Am. Chem. Soc. 2004, 126, 7144-7151). A stoichiometric amount of PPh3 was found to be required as the resultant F-Pd(PPh3)3 complex undergoes reductive elimination of F-PPh3, regenerating Pd(0) (V. V. Grustin Chem. Eur. J. 2002, 8, 1006-1014).