Visible‐Light Photoredox‐Catalyzed Tandem Trifluoro‐methylation/Cyclization/Remote Oxidation of 1,6‐Dienes: Access to CF₃‐Containing Five‐Membered Heterocycles

Abstract

A visible‐light photoredox‐catalyzed tandem trifluoromethylation/cyclization/remote oxidation of 1,6‐dienes has been achieved. A broad range of trifluoromethyl group‐containing tetrahydrofurans or tetrahydropyrroles could be generated in good yields and with excellent diastereoselectivity by using dimethyl sulfoxide (DMSO) as the oxidant. The mild and facile protocol affords direct access to trifluoromethyl group‐bearing tetrahydrofurans and tetrahydropyrroles via difunctionalization of olefins.magnified image

Carbotrifluoromethylations of C−C Multiple Bonds (Excluding Aryl‐ and Alkynyltrifluoromethylations)

“…After the application of Pd, a transition metal, in the method of Liu 33 , the copper-catalyzed synthesis for the formation of 3trifluoroethylated 4-aminochromans via intramolecular carbotrifluoromethylation of ene-imines was also published by Deng [35] Three years later, the photoredox-catalyzed tandem trifluoromethylation/cyclization/remote oxidation of 1,6-diene substrates leading to CF 3 -substituted five-membered heterocycles was developed by Zhu [36] and co-workers. Togni's reagent, Ir(ppy) 3 , and Na 2 HPO 4 were applied in the transformation giving the corresponding products with excellent diastereoselectivtiy in good yields (Scheme 27).…”

Recent Advances in Visible Light‐Mediated Radical Fluoro‐alkylation, ‐alkoxylation, ‐alkylthiolation, ‐alkylselenolation, and ‐alkylamination

“…Additional in vitro studies showcase the potential therapeutic benefits of the products for the treatment of diabetes. Also employing 38 , Zhu and coworkers provided the trifluoromethylation‐cyclization of 1,6‐dienes to form CF 3 ‐containing tetrahydrofurans and tetrahydropyrroles [162] . This cyclization involves a remote oxidation mediated by DMSO.…”

Theoretical study for evaluating and discovering organic hydride compounds as novel trifluoromethylation reagents

“…[1][2][3][4][5][6][7][8][9] All trifluoromethylation reagents 1,2 could be reasonably divided into nucleophilic trifluoromethylation reagents, 10,11 electrophilic trifluoromethylation reagents [12][13][14][15][16] and free radical trifluoromethylation reagents [17][18][19][20][21] according to their reaction mechanisms. Generally, nucleophilic trifluoromethyl reagents and electrophilic trifluoromethyl reagents need to be activated by light, catalysts or single electron donors/acceptors to generate key active free radical intermediates to provide • CF 3 (Scheme 1); [9][10][11][12][13][14][15][16] in fact, only a few examples are available as + CF 3 or − CF 3 transfer mechanisms. [22][23][24] 4-Substituted Hantzsch esters (XRH) have typical 1,4-dihydropyridine core structures, which also are classical NADH models and important organic hydride compounds (Scheme 2).…”

“…6–8 At present, important progress has been made in the discovery and application of trifluoromethylation reagents. 1–9 All trifluoromethylation reagents 1,2 could be reasonably divided into nucleophilic trifluoromethylation reagents, 10,11 electrophilic trifluoromethylation reagents 12–16 and free radical trifluoromethylation reagents 17–21 according to their reaction mechanisms. Generally, nucleophilic trifluoromethyl reagents and electrophilic trifluoromethyl reagents need to be activated by light, catalysts or single electron donors/acceptors to generate key active free radical intermediates to provide ˙CF 3 (Scheme 1); 9–16 in fact, only a few examples are available as + CF 3 or − CF 3 transfer mechanisms.…”