The Nucleophilic 5-endo-trig Cyclization of 1,1-Difluoro-1-alkenes: Ring-Fluorinated Hetero- and Carbocycle Synthesis and Remarkable Effect of the Vinylic Fluorines on the Disfavored Process

Abstract

The disfavored 5-endo-trig cyclizations have been accomplished for 1,1-difluoro-1-alkenes with nitrogen, oxygen, sulfur, and carbon nucleophiles by taking advantage of the properties of fluorine. β,β-Difluorostyrenes bearing tosylamido, hydroxy, or methylsulfinyl group at the o-position undergo intramolecular nucleophilic substitution with a loss of the vinylic fluorine, leading to 2-fluorinated indole, benzo[b]furan, and benzo[b]thiophene in high yields. 1,1-Difluoro-1-butenes bearing homoallylic tosyl­amido, hydroxy, mercapto, or iodomethyl group also successfully cyclize via a 5-endo-trig process with the in situ generated intramolecular nucleophiles to afford 2-fluoro-2-pyrroline, 5-fluoro-2,3-dihydrofuran, 5-fluoro-2,3-dihydrothiophene, and 1-fluorocyclo-pentene. The two vinylic fluorines proved to be essential and play a critical role in these ‘anti-Baldwin’ cyclizations.