A One-Pot Domino Reaction Providing Fluorinated 5,6-Dihydro-1,2-thiazine 1-Oxides from Sulfoximines and 1-Trifluoromethylstyrenes

Abstract

N-Trifluoroacetylated (N-TFA) sulfoximines react with 1-trifluoromethylstyrenes in a one-pot domino reaction to give fluorinated 5,6-dihydro-1,2-thiazine 1-oxides in good to high yields. The process involves three sequential reaction steps that can be characterized as (1) nucleophilic allylic substitution (S N 2′), (2) hydrolysis, and (3) intramolecular nucleophilic vinylic substitution (S N V). The products can further be modified by defluorination. The molecular structure of the resulting product was confirmed by X-ray crystallographic analysis.

“On-water” defluorinative cyclization of trifluoromethyl enones with phosphine oxides: synthesis of polysubstituted furans

“…Based on these findings and previous reports, 12,15–22,24 we propose a reaction mechanism (Scheme 3). Under basic conditions, the reaction of phosphoryl anion A with electrophilic trifluoromethyl enone 1 initially affords intermediate B , which undergoes rapid anionic F-elimination to form phosphorylated gem -difluoroalkene C .…”

“…2A, above). 15 In this mode, terminal CF 3 -substituted alkenes serve as versatile three-carbon fluorine-containing synthons, facilitating the accessibility of mono-fluorinated heterocycles. Furthermore, the presence of the carbonyl group attached to CF 3 -alkenes provides promising potential for adjusting reactivity and chemoselectivity.…”

Picking Two out of Three: Defluorinative Annulation of Trifluoromethyl Alkenes for the Synthesis of Monofluorinated Carbo‐ and Heterocycles

“…[34] Recently, the same group found that N-trifluoroacetylated (N-TFA) sulfoximines react with 1trifluoromethyl styrenes in a one-pot domino reaction, providing fluorinated 5,6-dihydro-1,2-thiazine 1-oxides in good yields (Scheme 8c). [35] With trifluoroacetyl as the protecting group, the hydrolysis of the C-gem-difluoroalkenylated products released the deprotected sulfoximines, which enables the intramolecular S N V reaction of N-nucleophile with gem-difluoroalkenes. The reaction provided a facile method to incorporate sulfoximidoyl groups into heterocyclic scaffolds.…”

“…When the N ‐atom of sulfoximines was protected by Bz (benzoyl), Ts (tosyl) or Ac (acetyl) group, C‐ gem ‐difluoroalkenylated products were obtained (Scheme 8b) [34] . Recently, the same group found that N ‐trifluoroacetylated ( N ‐TFA) sulfoximines react with 1‐trifluoromethyl styrenes in a one‐pot domino reaction, providing fluorinated 5,6‐dihydro‐1,2‐thiazine 1‐oxides in good yields (Scheme 8c) [35] . With trifluoroacetyl as the protecting group, the hydrolysis of the C‐ gem ‐difluoroalkenylated products released the deprotected sulfoximines, which enables the intramolecular S N V reaction of N ‐nucleophile with gem ‐difluoroalkenes.…”