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

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

      3.2.1.3 Aminium Radical Cation Addition

Electrophilic addition of aminium radical cations to unsaturated C=C bonds represents another attractive approach for the C—N bond construction. Generally, in visible‐light‐induced reactions, direct SET oxidation of the N—H bonds by the excited photocatalysts affords the crucial aminium radical cation intermediates, which are further converted into α‐amino radicals after addition to unsaturated C=C bonds to allow the C—N bond formation. In this field, representative work has been demonstrated independently by the research groups of Zheng and Knowles.

In 2012, Zheng's group disclosed a visible‐light‐induced intramolecular C—N bond formation/cyclization reaction of styryl diarylamines 60 and 62 to prepare N‐arylindoles 61 and 63 under the irradiation of a white light‐emitting diode (LED) and ambient conditions (Scheme 3.10) [23]. Interestingly, a 1,2‐carbon shift process is observed in the reaction of substrates 62 with their C2 position fully occupied, affording R¹‐shifted indole products 63 in moderate yields, wherein aryl groups are preferentially transferred over alkyl groups (63a). A reasonable reaction scope is presented, covering various substrates with electron‐donating or electron‐withdrawing substituents on Ar₁, as well as a wide range of substituents on C2 and C3 (61a–61e). Moreover, the R¹‐migration process represents an elegant strategy for ring expansion (63b). Nevertheless, functional groups on Ar₂ are limited to para‐alkoxy ones to facilitate their effective oxidation.

Scheme 3.10 Photocatalytic C—N bond formation for the preparation of N‐arylindoles.

      Source: Modified from Maity and Zheng [23].

A plausible mechanism for the above photocatalytic transformation is proposed in Scheme 3.11. The reaction occurs with the oxidation of substrate 60 by the excited state photocatalyst Ru^II* to generate the key aminium radical cation 64. The subsequent intramolecular electrophilic addition of 64 to its tethered C=C bonds affords intermediate 65, which then turns into benzylic radical 66 after a proton abstraction. The oxidation into the corresponding benzylic cation 67 and the further aromatization of 67 upon deprotonation finally result in the desired N‐arylindole 61. As for substrate 62, the reaction proceeds through the same pathway before reaching benzylic cation 68. Then, a 1,2‐carbon shift event follows, in which one of the substituents on C2 migrates onto C3, providing cationic intermediate 69, which is further deprotonated to deliver the final product 63.

Thereafter, the authors applied this intramolecular C—N bond formation strategy and the same privileged structure to another photoredox cyclization protocol, in which two aliphatic rings are formed in one step to furnish fused indolines 71 (Scheme 3.12) [24]. Herein, remote nucleophilic functional groups such as –OH and –NHBoc are installed at the C2 position of the 2‐styryl anilines 70 to attack the in situ generated benzylic carbocations, and the desired cyclization products 71 are successfully obtained under photocatalytic conditions similar to their previous work.

Scheme 3.11 Mechanistic proposal for the photocatalytic synthesis of N‐arylindoles.

Scheme 3.12 Visible‐light‐initiated tandem reaction for the synthesis of fused N‐arylindolines.

      Source: Modified from Morris et al. [24].

In 2014, an intramolecular anti‐Markovnikov hydroamination protocol of aryl olefins was disclosed by Knowles' group, for the construction of structurally diverse N‐aryl heterocycles 73 in a simple reaction system under mild photocatalytic conditions (Scheme 3.13) [25]. The reaction is proposed to begin with the direct oxidation of aniline 72 by the photoexcited catalyst Ir^III* to generate the crucial aminium radical cation 74, as supported by both CV data and luminescence quenching experiments. The following sequence of the intramolecular addition to the tethered alkene of intermediate 74, the one‐electron reduction of benzylic radical 75 by Ir^II, and the proton transfer from alcoholic solvent to 76 delivers the final product 73. A wide range of substrates bearing various substituents on both aromatic groups (Ar¹ and Ar²) are proven compatible with this method, providing cyclization products in good to excellent yields, including five‐ or six‐membered, heterocylic, and bicyclic ones (73a–73h). However, application of this protocol to intermolecular couplings turned out to be unsuccessful, which is likely due to the fact that the bimolecular C—N bond formation fails to outcompete the favorable electron back‐transfer from the Ir^II complex to the aminium intermediate, as speculated by the authors.

Scheme 3.13 Photocatalytic intramolecular hydroamination of olefins with aminium radical cations.

      Source: Modified from Musacchio et al. [25].

With their further exploration into photocatalytic amination of alkenes, Knowles and coworkers next developed an intermolecular anti‐Markovnikov hydroamination of unactivated alkenes 78 with secondary aliphatic amines 77, which is not accessible using their previous protocol ( Скачать книгу