Organic Photoredox-Catalyzed Synthesis of δ-Fluoromethylated Alcohols and Amines via 1,5-Hydrogen-Transfer Radical Relay

Abstract

The hydrotrifluoromethylation of benzyl-protected homoallylic alcohol and amine derivatives catalyzed by 2,4,5,6-tetra­(9H-carbazol-9-yl)­isophthalonitrile (4CzIPN) was developed. This reaction delivered δ-fluoromethylated free alcohols and amines with in situ deprotection of benzyl protecting group under mild irradiation conditions. 4CzIPN was found to be a competent metal-free photoredox catalyst for activating several types of fluoromethylation reagents including CF3SO2Cl, Togni’s reagent, and 2-bromo-2,2-difluoroacetate via oxidative quenching and also CF3SO2Na through reductive quenching to allow direct hydrotrifluoromethylation of simple alkenes and Michael acceptors.

Recent Synthetic Applications of the Hypervalent Iodine(III) Reagents in Visible-Light-Induced Photoredox Catalysis

“…Xu and coworkers developed a method of hydrotrifluoromethylation of benzyl-protected homoallylic alcohol and amine derivatives employing Togni's reagent as the CF 3 radical source under organic photoredox catalysis (Wang et al, 2019 ) ( Figure 3C ). Togni's reagent was found to be a more effective trifluoromethylation reagent than CF 3 SO 2 Cl in the reaction.…”

Frontiers in Radical Fluoromethylation by Visible‐Light Organic Photocatalysis

“…Koike and Akita group reported the keto‐trifluoromethylation of aromatic alkene 40 using 4 t Bu−BDA ((9,10‐bis( p ‐ t Bu−diphenylamino)anthracene)) (Scheme b) . In 2019, Zhang and Xu showed that 4CzIPN induces hydro‐trifluoromethylation of benzyl‐protected homoallylic alcohols and amines 42 concomitant with deprotection through HAT of the radical intermediate A (Scheme c) …”

“…[26] In 2019, the Zhang and Xu group reported the 4CzIPN-catalyzed hydrodifluoromethylation of homoallylic amine 19 (Scheme 7b). [27] Scheme 8 shows the MesÀ Acr + -catalyzed monofluoromethylation of isocyanides 21 with 3 a in the synthesis of CH 2 Fcontaining phenanthridines 22 developed by the Ao and Liu group. In addition, the reaction system was applied to the reactions with 1 a and 2 a.…”

“…[49] In 2019, Zhang and Xu showed that 4CzIPN induces hydro-trifluoromethylation of benzyl-protected homoallylic alcohols and amines 42 concomitant with deprotection through HAT of the radical intermediate A (Scheme 14c). [27] Scheme 11. Radical trifluoromethylation with 1 c by Eosin Y and AcrH 2 .…”

“…reported the Eosin Y‐catalyzed direct difluoromethylation of coumarins 17 (Scheme a) . In 2019, the Zhang and Xu group reported the 4CzIPN‐catalyzed hydro‐difluoromethylation of homoallylic amine 19 (Scheme b) . Scheme shows the Mes−Acr + ‐catalyzed monofluoromethylation of isocyanides 21 with 3 a in the synthesis of CH 2 F‐containing phenanthridines 22 developed by the Ao and Liu group.…”