(177) are employed as the N–H nucleophiles to approach a variety of phenethylamine derivatives 178. In line with their previous work on nucleophilic alkene functionalization, the authors suggest that the key step is the SET process between alkene 176 and the photoexcited acridinium (Mes‐Acr+*), which results in the generation of key radical cation intermediate 179. Subsequently, nucleophiles TfNH2 or 177 undergo reversible addition to the least‐substituted side of 179 to form the stabilized C‐radical 180, which may further undergo a HAT process with a hydrogen atom donor, presumably thiophenol, to deliver the desired product 178. On the other hand, the putative HAT reagent thiophenol is supposed to come from phenyl disulfide after a homolysis/single‐electron reduction/protonation sequence.
In 2017, Lei and coworkers developed an external oxidant‐free photocatalytic CDC amination and etherification of alkenes with azoles and alcohols using a dual catalytic system combining photocatalyst Mes‐Acr+ClO4− and a Co‐based cocatalyst (Scheme 3.32) [46]. The single‐electron oxidation of alkene 181 by the photoexcited Mes‐Acr+* is considered as the key initial step, providing Mes‐Acr· and radical cation species 186. Subsequently, the employed nucleophile 182 (or 183) reacts with 186 to form the more stable radical intermediate 187, which is further oxidized into the corresponding cationic species 188 by either Mes‐Acr+* or CoIII. Then, the final anti‐Markovnikov product 184 (or 185) is delivered after deprotonation of 188. As for the Co catalytic cycle, the reduced CoII undergoes further reduction by Mes‐Acr· to yield CoI species, which is protonated twice and then releases one molecule H2 to regenerate the CoIII species.
Scheme 3.31 Anti‐Markovnikov hydroaminations of alkenes by two component organic photoredox systems.
Source: Modified from Nguyen and Nicewicz [44].
Scheme 3.32 Photocatalytic dehydrogenative cross‐coupling of alkenes with azoles and alcohols via a dual catalytic system.
Source: Modiifed from Yi et al. [46].
In 2018, again in Lei's laboratory, a photoinduced oxidative [4+2] annulation of imines and alkenes was developed by utilizing a dual photoredox/cobaloxime catalytic system in a mixed solvent of 1,2‐DCE and hexafluoroisopropanol (HFIP) (Scheme 3.33) [47]. This method not only obviates the application of stoichiometric oxidants but also exhibits excellent atom economy by generating hydrogen gas as the only by‐product, achieving high regioselectivity and trans‐diastereoselectivity even if alkenes are employed in Z/E mixtures. On the basis of Stern–Volmer studies and CV experiments, a plausible mechanism is proposed. Firstly, single‐electron oxidation of 190 by the excited‐state photosensitizer leads to the generation of the alkene radical cation intermediate 192 and to the reduced Mes‐Acr·. Subsequently, the nucleophilic attack of 189 furnishes the radical 193 after deprotonation, in which the C=C single bond prefers a more stable trans‐configuration upon rotation as proposed by the authors. Next, the radical cyclization of 193 gives the intermediate 194, which is further oxidized to furnish 195. After elimination of a proton, the desired 3,4‐dihydroisoquinoline product 191 is afforded. On the other hand, the reduced photosensitizer is oxidized by the CoIII species to complete the photoredox catalytic cycle. As for the cobalt side, the CoII species is reduced to form a CoI intermediate, which can be protonated to produce CoIII‐hydride. The CoIII‐hydride species would then release H2 upon the interaction with protons.
Scheme 3.33 Photoinduced oxidative [4+2] imine/alkene annulation with H2 liberation.
Source: Modified from Hu et al. [47].
3.3.3 Activated C(sp3)—H Bond Amination
In the early years, C(sp3)–H amination reactions were mainly achieved via transition metal catalysis or with hypervalent iodine reagents. Recently, quite a few methods for CDC amination of activated C(sp3)—H bonds, such as benzylic C(sp3)–H and C(sp3)–H in α-position to a nitrogen atom, have been realized via the formation of the corresponding cationic species and subsequent addition of nitrogen nucleophiles by means of photo/electrochemistry.
3.3.3.1 Benzylic C(sp3)—H Bond Amination
As an example for the direct amination of benzylic C(sp3)—H bonds, Pandey's group disclosed a photocatalytic CDC amination of alkylbenzenes 196 with N‐methoxyamides 197 under metal‐free and external oxidant‐free conditions (Scheme 3.34) [48]. The 410 nm wavelength visible light source is obtained by using a combination of Pyrex and a CuSO4:NH3 solution filter from a 450 W Hanovia medium pressure lamp. Compound 9,10‐dicyanoanthracene (DCA) is employed as a photosensitizer, which facilitates an array of C(sp3)–H amination reactions between 196 and 197 with good functional group tolerance (198a–198f). Notably, this protocol is also applicable to intramolecular C—N bond construction to provide five‐membered rings (198g). The mechanistic proposal is depicted in Scheme 3.34b. First, the single‐electron oxidation of 197 by the photoexcited DCA* yields the N‐methoxyamide radical cation 199, which then converts into radical intermediate 200 after deprotonation. The following HAT process from the benzylic position of alkylbenzene 196 to radical 200 regenerates 197 and meanwhile gives benzylic radical 201. The subsequent oxidation of 201 generates benzylic cation 202, which further reacts with 197 to deliver the desired amination product 198. The results of control experiments and some experimental observations add credit to this putative mechanism. For example, the existence of N‐centered radical intermediate 200 is suggested by the formation of its dimeric product, while benzylic radical 201 is captured by TEMPO in a radical trapping experiment. To demonstrate the intermediacy of benzylic cation 202, the authors performed the model reaction using a mixture of MeCN/AcOH (9 : 1) as the solvent, which provides the desired 198 in diminished yield, along with the by‐product benzyl acetate in 10% yield.
