Tailoring the Reactivity of the Langlois Reagent and Styrenes with Cyanoarenes Organophotocatalysts under Visible‐Light

Abstract

The selective one-step access to fluoroalkylated hexestrol derivatives, nonsteroidal estrogens, is achieved in good to excellent isolated yields under organophotoredox conditions by using the stable and easy to handle Langlois reagent.Furthermore, the challenging selective hydrotrifluoromethylation of styrenes proceeds under mild reaction conditions without the requirement for any additive. We assume that the solvent drives the reaction pathway towards either the reduction or the dimerization of the radical intermediate generated after initial addition of the fluoroalkyl radical to the styrene. The versatility of the developed system is also extended to encompass radical-radical cross-coupling as exemplified here using cyanopyridine. Mechanistic investigations including luminescence and EPR spectroscopy allow to shed the light on the different mechanisms.

Evolution and Future of Hetero‐ and Hydro‐Trifluoromethylations of Unsaturated C−C Bonds

“… [172] The conditions could be applied to the intramolecular hydro‐trifluoromethylation of benzyl‐protected homoallyl alcohol and amine derivatives ( vide infra , Scheme 187). Very recently, a similar reaction using DMSO instead of 1,4‐dioxane−MeOH as the solvent has been demonstrated by Tlili and coworkers [173] . Under these conditions, the formation of a carbanion intermediate during reductive quenching was proposed.…”

Langlois Reagent: An Efficient Trifluoromethylation Reagent

“…This method afforded the products with 30-80% yields. 12 This article is protected by copyright. All rights reserved.…”

“…This method afforded the products with 30-80% yields. 12 Liu et al developed a transition-metal-free, graphene oxide (GO) catalyzed direct C-H trifluoromethylation of alkynes and quinoxalinones with Langlois reagent that afforded the trifluoromethylated quinoxalin-2(1H)-one product under ambient atmosphere. 13 Tang et al have demonstrated the first Fe-catalyzed regioselective perfluoromethylalken-and alkynylation of 1,4-naphthoquinones using NaSO₂CF₃ and K 2 S 2 O 8 as an oxidant.…”

Photocatalyzed 2∶2 Coupling of Styrene and BrCF2CO2Me: A Facile Synthesis of Bis-difluoroacetylated Hexestrol Derivatives

“…Homo-coupling reaction of styrene derivatives mediated by the addition of CF 3 radical could also afford fluorine-substituted hexestrol, but it could only be observed by GC-MS or separated as one by-product. [9] Recently, Tlili and co-workers [10] reported a photocatalyzed strategy using R F SO 2 Na (R F ＝CF 3 , CF 2 H, CF 2 H) and styrenes as substrates, which successfully afforded 1,4-(CF 3 ) 2 hexestrols, as well as 1,4-(CF 2 H) 2 and 1,4-(CFH 2 ) 2 products (Scheme 1c). Method to efficiently introduce bis-difluoroacetate into the hexestrol skeletal is rarely reported, only one example obtaining diethyl 2,2, 7,7-tetrafluoro-4,5-dimethyl-4,5-diphenyloctanedienoate in 60% yield with stoichiometric copper reagent and high temperature has been reported.…”