Anti-Diastereoselective Synthesis of CF₃-Containing Spirooxazolines and Spirooxazines via Regiospecific Trifluoromethylative Spirocyclization by Photoredox Catalysis

Abstract

A novel synthesis of CF3-containing spirooxazolines and spirooxazines has been developed. Regiospecific trifluoromethylative spirocyclization (CF3-spirocyclization) of cyclic alkenes bearing an amide pendant mediated by photoredox catalysis is a useful strategy for construction of a C(sp(3))-CF3 bond and an spirooxazoline or spirooxazine ring onto C═C bonds via a single step. The key intermediate is α-CF3-substituted carbocationic species smoothly generated from single-electron-transfer (SET) photoredox processes, which results in diastereoselective spirocyclization. This is the first example of synthesis of CF3-containing spirooxazolines and spirooxazines in anti-fashion with respect to the CF3 group and the oxygen atom of the spirocycles.

Recent advances in photoinduced trifluoromethylation and difluoroalkylation

“…Synthesis of oxazolines by using Umemoto's reagent 1c There were two similar examples by using N--allylamides as the oxygen nucleophiles, as reported by the groups of Xiao 23 and Akita. 24 In these two reports, the exo--type of products were generated. Xiao and co--workers 23 described the synthesis of oxazolines/benzoxazines under mild conditions (Scheme 15).…”

The dual role of thiourea in the thiotrifluoromethylation of alkenes

“…> 20 : 1). 17 The 1,2-dihydro-naphthalene scaffold was selected to investigate the tolerance of the reaction to variation of the thiourea N- substituent. The resulting products anti- 2ga–2gl were isolated in yields ranging from 53% to 83%.…”

Light on Unsaturated Hydrocarbons – “Gotta Heterofunctionalize Them All”

“…The Akita and Koike group then expanded the scope of the intramolecular version of this oxytrifluoromethylation to amide substituents (Scheme 64). [77] Owing to the very good diastereoselectivity of this method, they achieved the first predominant formation of the anti diastereoisomers of CF 3 -containing spirocyclic compounds. Various amido substrates were reacted with either aliphatic (351) or aromatic substituents (352 to 354).…”