In 2019, an electrochemical alternative was disclosed by Wu and coworkers, wherein exclusive ortho‐selectivity of amination was achieved in the most cases, under metal‐ and oxidant‐free conditions (Scheme 3.27) [40]. During the optimization of the reaction conditions using anisole 151a and pyrazole 152a, the authors found that the addition of trifluoroacetic acid (TFA) could effectively enhance the ortho‐regioselectivity. Similarly, in the subsequent scope evaluation, it was also observed that reactions with TFA provided significantly higher o:p selectivity than the corresponding ones without it (153a, 153d, and 153e). The proposed mechanism is depicted in Scheme 3.27b. Anisole 151a is preferentially oxidized to provide the radical cation 154a at the anode, after which pyrazole 152a as a nucleophile attacks 154a to form the ortho‐aminated intermediate 156a via a putative intermediate 155a with TFA‐assisted hydrogen bond interaction. Final product 153a is formed after deprotonation and rearomatization of 156a.
Scheme 3.25 Photoinduced oxidant‐free C–H amination of arenes with azoles.
Source: Modified from Niu et al. [38].
Scheme 3.26 Selective C–H amination of electron‐rich arenes via photoredox catalysis.
Source: Modified from Pandey et al. [39].
Scheme 3.27 Electrochemical ortho‐amination of aromatic C—H bonds with azoles.
Source: Modified from Wang et al. [40].
Electron‐rich pyrroles and thiophenes can easily be oxidized into their corresponding radical cations to undergo further C—N bond formation processes via N‐atom nucleophilic addition pathway. In 2016, König and coworkers realized a photocatalytic C(sp2)–H sulfonamidation of pyrroles to reach a range of N‐(2‐pyrrole)sulfonamides 159 (Scheme 3.28) [41]. In this transformation, N‐substituted pyrrole 157 is first oxidized by the photoexcited organic dye Mes‐Acr+ into its corresponding radical cation 160, which is attacked by strong anionic nucleophile 161, resulting from deprotonation of sulfonamide 158 to generate radical intermediate 162. The final amination product 159 is afforded via a HAT process with O2·− or alternatively through further oxidation and deprotonation sequence of 162.
Scheme 3.28 Direct C2‐sulfonamidation of pyrroles via visible‐light photoredox catalysis.
Source: Modified from Meyer et al. [41].
Scheme 3.29 DDQ‐mediated C2‐amination of thiophenes via visible‐light photoredox catalysis.
Source: Modified from Song et al. [42].
In the following year, Lei and coworkers disclosed a photocatalytic C(sp2)–H amination of thiophenes with azoles, employing 2,3‐dicyano‐5,6‐dichlorobenzoquinone (DDQ) as an organic photocatalyst, tert‐butyl nitrite (TBN) as an electron transfer mediator, and aerobic oxygen as the oxidant (Scheme 3.29) [42]. The photoexcited catalyst DDQ* upon visible light irradiation possesses a high oxidation potential (Ered = 3.18 V vs. saturated calomel electrode [SCE]) and thus can easily oxidize thiophene 163 into radical cation 166. Nucleophilic addition by azole 164 and the following proton donation to DDQ·− convert radical cation 166 into radical intermediate 167, which undergoes further HAT process with the formed DDQH· to yield the desired products 165 and DDQH2. To complete the photocatalytic cycle, DDQH2 then participates in another cycle involving TBN to regenerate the original photocatalyst DDQ.
Scheme 3.30 Photocatalytic benzene C–H amination and hydroxylation with hydrogen evolution.
Source: Modified from Zheng et al. [43].
Apart from the most widely used N–H nucleophile azoles, ammonia as an abundantly available and cheap reagent has also attracted attention of researchers, and has been exploited in nucleophilic CDC amination. In 2016, Wu and Tung and coworkers developed a dual catalytic cross‐coupling between aromatic C—H bonds and ammonia or water under visible‐light conditions to furnish anilines or phenols with the evolution of hydrogen gas (Scheme 3.30) [43]. N‐Methylquinolinum salts QuCN+ClO4− and QuH+ClO4− are employed as the photocatalysts (QuR+), whose the excited states possess enough oxidizing power (Ered* = 2.72 and 2.46 V vs. SCE, respectively) to accept an electron from benzene (Eox = 2.48 V vs. SCE) to furnish the reduced photocatalyst QuR· along with the crucial radical cation 171. Subsequently, the former is oxidized by CoIII catalyst to regenerate the ground‐state photocatalyst QuR+; meanwhile, the latter is captured by a nucleophile to form radical 172, which further donates an electron to CoII to produce cationic species 173. The final product 170 is formed after further deprotonation of 173. On the basis of CV studies, the redox potential values demonstrate that product 170 is also capable of quenching the excited photocatalyst QuR+*, which may result in its further functionalization. However, mono‐functionalized benzene is obtained as the only product, and no multiaminated or hydroxylated products can be detected even after prolonged reaction time. A hypothesis for this result, advanced by the authors, is that the rapid back‐electron transfer from the reduced QuR· to the formed radical cation of 170 protects product 170 from overoxidation.
3.3.2 Olefinic C(sp2)—H Bond Amination
As