Visible‐Light Photoredox‐Catalyzed C−H Difluoroalkylation of Hydrazones through an Aminyl Radical/Polar Mechanism

Abstract

An unprecedented visible-light-induced direct C-H bond difluoroalkylation of aldehyde-derived hydrazones was developed. This reaction represents a new way to synthesize substituted hydrazones. The salient features of this reaction include difluorinated hydrazone synthesis rather than classical amine synthesis, extremely mild reaction conditions, high efficiency, wide substrate scope, ease in further transformations of the products, and one-pot syntheses. Mechanistic analyses and theoretical calculations indicate that this reaction is enabled by a novel aminyl radical/polar crossover mechanism, with the aminyl radical being oxidized into the corresponding aminyl cation through a single electron transfer (SET) process.

Room-Temperature Direct Arylation of Anilides under External Oxidant-Free Conditions Using CO2-Derived Dimethyl Carbonate (DMC) as a ′Green′ Solvent

“…Based on preliminary results and known literature precedent, a plausible catalytic cycle may involve the following key steps, (i) photoexcitation of Ru(bpy) 3 2+ catalyst to generate a triplet state Ru(bpy) 3 2+* (E R ° =‐0.81 V/SCE), (ii) the standard reduction potential of different ArN 2 BF 4 are very close to SCE varying from a small positive to negative values, and can be easily reduced by the triplet Ru(bpy) 3 2+* to aryl radical (Ar ⋅ ) with the concomitant oxidation of Ru center to Ru(bpy) 3 3+ , (iii) reaction of aryl radical (Ar ⋅ ) with palladacycle, (iv) one‐electron oxidation of palladacycle by Ru(bpy) 3 3+ (E R ° =+1.29 V/SCE) to regenerate the photocatalyst, and finally, (v) C−C bond formation via reductive elimination to release 3 and regeneration of Pd catalyst. Notably, an alternative mechanism involving binuclear palladium species that may result in completely different catalytic cycle can't be rolled out…”

Recent advances in photoinduced trifluoromethylation and difluoroalkylation

“…Difluoroalkylation of hydrazones involving C--H bond cleavage via an aminyl radical/polar mechanism was reported by Zhu and co--workers (Scheme 48). 60 A range of functional groups attached to hydrazones was tolerated under the reaction conditions. Two hypothesis were proposed, which would probably undergo through aminyl radical/polar mechanism and carbon radical/polar mechanism.…”

Photocascade Catalysis: A New Strategy for Cascade Reactions

“…It has been well established that activated bromides can be transformed into various reactive carbon radicals through photoredox‐catalyzed SET reduction . On the basis of their previous work on the visible light photocatalytic C(sp 2 )−H difluoroalkylation of aldehyde hydrazones, Zhu and co‐workers next developed a cascade alkylation of C(sp 2 )−H and C(sp 3 )−H bonds of aldehyde hydrazones 33 using readily available and simple 2,2‐dibromo‐1,3‐dicarbonyls 34 by visible‐light photocascade catalysis (Scheme ) . This procedure provides a mild and efficient approach to highly functionalized and complex fused dihydropyrazole derivatives 35 .…”