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Scheme 3.14 Photocatalytic intermolecular hydroamination of unactivated olefins with secondary alkyl amines.

      Source: Modified from Musacchio et al. [26].

The mechanism proposed by the authors is depicted in Scheme 3.14b. As supported by Stern–Volmer experiments, piperidine 77a can effectively quench the photoexcited Ir^III* to produce the N‐centered radical cation species 80a, which then adds onto an alkene acceptor, e.g. 78a, to form a new C—N bond along with an adjacent C‐radical (81a). Differently from their previous amination protocol (Scheme 3.13), intermediate 81a then abstracts a hydrogen atom from the TRIP thiol cocatalyst to deliver a closed‐shell ammonium ion 82a and a transient thiyl radical (ArS^·). Subsequently, a SET process takes place between ArS^· and the reduced Ir^II species to provide ArS⁻ and the regenerated ground‐state photocatalyst Ir^III. The final hydroamination product 79a is furnished after the deprotonation of 82a by anion ArS⁻. According to the obtained redox potentials, the final products 79 could possibly be further oxidized by the excited Ir^III*, but high yields of 79 have still been obtained in these transformations without meaningful amounts of decomposition. The authors speculate that this outcome may result from the protective action of the thiol cocatalyst by reducing any α‐amino radical that could be engaged in further deleterious side reactions.

Again in 2019, an intermolecular anti‐Markovnikov hydroamination of unactivated olefins 84 was achieved by Knowles' group, using simple primary alkyl amines 83 under mild photoredox conditions (Scheme 3.15) [27]. An identical mechanism to the former one via an aminium radical cation intermediate 86 is proposed for this transformation employing a different iridium photocatalyst with divergent reactivity. Despite the presence of excess olefin, high selectivities, generally over 20 : 1, are observed for secondary over tertiary amine products.

In the typical visible‐light‐induced reactions described above, the photoredox catalysts harvest visible light to reach their excited states, which then undergo further single‐electron redox events with reactants. Recently, a new photoactivation paradigm has emerged, wherein the transition‐metal‐based photocatalysts also directly engage in the bond formation/cleavage processes. In this area, a growing number of photoinduced C—N bonds forming methodologies using Cu‐based unconventional photocatalysts have lately been developed by Fu, Hwang, Kobayashi, etc., and their progresses have been summarized by Gevorgyan in 2017 [28]. As an example, Hwang and coworkers reported a visible‐light‐induced, Cu‐catalyzed reaction for the preparation of α‐ketoamides from anilines 87 and alkynes 88 under ambient conditions (Scheme 3.16) [29]. Using oxygen as a green oxidant, this ligand‐ and base‐free method features high atom economy and is compatible with a wide range of aniline and alkyne substrates. Notably, bioactive epoxide hydrolase inhibitors 89i and 89j are smoothly prepared within a single step from commercial starting materials by means of this strategy.

A plausible pathway is proposed on the basis of a series of detailed mechanistic studies (Scheme 3.17). Via a weak Cu^I–aniline complex formed by catalyst CuCl and aniline 87, Cu^I–phenylacetylide 90 is generated upon the addition of alkyne 88, which then reaches its excited state 91 under blue light irradiation. The following SET oxidation of 91 by O₂ provides an electron‐deficient Cu^II–phenylacetylide 92 as well as a superoxide. The following nucleophilic addition of aniline 87 to complex 92 results in the Cu^III species 93, which next undergoes reductive elimination to furnish the highly reactive Cu^I‐coordinated ynamine 94. The intermediate 94 readily reacts with O₂ to generate the Cu^II peroxo‐complex 95, which then tautomerizes into the Cu^I species 96. Finally, complex 96 is attacked by Cl⁻ to regenerate the catalyst CuCl, and the subsequent ring cleavage of the resulting intermediate 97 furnishes the final α‐ketoamide product 89.

Scheme 3.15 Photocatalytic intermolecular anti‐Markovnikov hydroamination of unactivated olefins with primary alkyl amines.

      Source: Miller et al. [27].

Scheme 3.16 Photoinduced, CuCl‐catalyzed oxidative C–N coupling of anilines with terminal alkynes.

      Source: Modified from Sagadevan et al. [29].

Scheme 3.17 Proposed mechanism for the photoinduced, CuCl‐catalyzed C–N coupling of anilines with terminal alkynes.

      3.2.2 Radical Species Addition to Aromatic Rings

      In the early years, the direct oxidative aminations of unfunctionalized arenes were achieved using iodine‐based reagents by the research groups of DeBoef, Chang, and Antonchick, wherein the employed amine partners were mainly sulfonamides and phthalimides. With the development of photoredox and electrochemical methodologies, more and more sustainable synthetic alternatives have emerged for the direct C(sp²)—N bond formation of simple arenes via N‐radical species addition pathways.

In 2016, Yu and Zhang and coworkers reported a visible‐light‐induced CDC amination of heteroarenes 98 with sulfonamides 99 using bleach (aqueous NaClO solution) as the oxidant (Scheme 3.18) [30]. Multiple heteroarenes such as indoles, pyrroles, and benzofurans can undergo this transformation with N‐methyl‐para‐toluene sulfonamide to afford their corresponding

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