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Hydrazones are also competent N‐radical precursors under basic conditions. Since 2014, β,γ‐unsaturated hydrazone 43 has been chosen by Xiao's group as a substrate to study a series of visible‐light‐induced intramolecular cyclization reactions, for the synthesis of various dihydropyrazole or dihydropyridazine derivatives (Scheme 3.8a). Mechanistically, the acidic N—H bond of 43 can be readily deprotonated by a base such as NaOH or K₂CO₃, and the resulting anionic species 44 is prone to SET oxidation to generate the crucial radical intermediates 45. Next, there are two R⁴‐dependent scenarios, 5‐exo‐trig or 6‐endo‐trig cyclization, for the further transformation of N‐radical 45 to access the corresponding radical intermediate 46 or 47, which can finally transform into diversified five‐ or six‐membered products after variable processes such as HAT, radical addition, etc.

The first work in this series is an intramolecular hydroamination of 43 bearing terminal alkenes, which was developed in 2014 (Scheme 3.8b) [17]. The desired product 48 is produced from the five‐membered intermediate 46 via a HAT process with the reaction solvent CHCl₃, which is demonstrated by a deuterium‐labeling experiment using CDCl₃ as the solvent. Moreover, radical 46 can also be intercepted by scavengers such as 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) and diphenyltelluride (PhTeTePh) to form the corresponding adducts. In the second work published in 2016, the substituent R⁴ of 43 is an aromatic group, instead of a hydrogen atom, giving access to 1,6‐dihydropyridazines 49 under photoredox conditions, which is facilitated by a TEMPO‐mediated HAT process [18]. As calculated by DFT, the additional Ar‐group significantly lowers the activation free energy of a 6‐endo‐trig cyclization pathway and simultaneously stabilizes the formed intermediate 47. On the basis of these previous findings, Xiao and coworkers next set out to expand this N‐radical formation strategy of diversely substituted β,γ‐unsaturated hydrazones to other cascade transformations, including the synthesis of dihydropyrazole‐fused benzosultams 50 through the addition of radical 46 to the aromatic ring of the pendant –Ts group [19], the synthesis of –OH‐functionalized pyrazoline 51a or pyridazine 51b through trapping of oxygen by the radical intermediate 46 or 47 [20], and the synthesis of 52a or 52b via the addition of radical 46 or 47 to allyl sulfones [21].

In 2016, another hydrazonyl radical‐based photoredox amination followed by a Smiles rearrangement was reported by Belmont's research group, wherein the N—H bond activation strategy is similar to that in Xiao's work (Scheme 3.9) [22]. Phthalazine derivatives 54 with varied substituents are obtained from alkynyl‐substituted sulfonyl hydrazones 53 under basic conditions with the extrusion of SO₂ (Scheme 3.9a). In light of the mechanistic studies including CV and fluorescence quenching experiments, it is proposed that the photoexcited catalyst Ru^II* undergoes one‐electron reduction with anion 55, generated by deprotonation of substrate 53 by the base NaOH. Subsequently, the produced N‐radical 56 cyclizes onto its tethered alkyne to form vinylic radical 57, which is further engaged in a radical Smiles rearrangement to yield a delocalized radical species 58 after the loss of one molecule of SO₂. After acquiring an electron from Ru^I species to complete the photoredox catalytic cycle, radical 58 is reduced to anionic species 59, which is then protonated by the protic solvent EtOH to deliver the final product 54 (Scheme 3.9b). Furthermore, the quantum yield of this reaction is measured as Φ = 0.33, which excludes a radical chain propagation process during the transformation. Additionally, attempts to realize one‐pot amination/Smiles rearrangement sequences by preparing 53 in situ from the corresponding aldehydes and sulfonyl hydrazides also succeeded, with the same efficiency compared with the original two‐step protocol (Scheme 3.9c).

Scheme 3.8 Applying hydrazonyl radical for C—N bond formation in photochemistry.

Source: Modified from Hu et al. [17].

Scheme 3.9 Visible‐light‐enabled access to phthalazine derivatives via an amination/Smiles rearrangement cascade.

Source: Modified from Brachet et al. [22].