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Scheme 1.21 Cu‐catalyzed C–H amination of heterocycles.

      Source: Matsuda et al. [28].

1.3 Electrophilic Amination Reactions Catalyzed by Other Transition Metals

Although the current focus of TM‐catalyzed electrophilic amination is copper catalysis, other transition metal complexes are also capable of serving as catalysts in these reactions.

Complexes of both Ni and Co can catalyze the electrophilic amination of organozinc reagents. The reaction mechanism is similar to the Cu‐catalyzed reactions; that is, the N—O or N—Cl bond of the aminating reagent undergoes cleavage when the metal enters into it via oxidative addition. The Johnson [31], Jarvo [32], and Knochel [33] groups reported their findings in several publications (Scheme 1.22).

J.‐Q. Yu and coworkers (The Scripps Research Institute) have successfully combined the Pd‐catalyzed C–H activation and electrophilic amination. Both sp² (Scheme 1.23) and sp³ (Scheme 1.24) C—H bonds can be aminated with this process. Mechanistically, these reactions proceed via a Pd(II)/Pd(IV) cycle: after the C–H activation, the resulting Pd(II) complex oxidatively inserts into the N—O bond of the aminating reagent, which is followed by a reductive elimination to form the new C—N bond. In some cases, it is necessary to add a Ag(I) salt as a sacrificial oxidant to help establish the catalytic cycle [34, 35].

The Yu group also demonstrated that rhodium and ruthenium complexes can also catalyze these types of reactions via similar mechanisms (Scheme 1.25) [36].

Apart from using a directing group in the C–H functionalization process, Catellani‐type reactions can also achieve directed C–H activation without the use of amide‐type directing groups. Dong and coworkers applied this strategy in the development of Pd‐catalyzed electrophilic amination reactions (Scheme 1.26) [37]. The main difference between this transformation and the standard Buchwald–Hartwig protocol is that the C–H group adjacent to the aryl halide moiety (i.e. the ortho position) gets aminated, while in the Buchwald–Hartwig reactions, the C—X bond itself gets aminated (i.e. the ipso position).

Scheme 1.22 Electrophilic amination catalyzed by other transition metals.

      Source: Johnson and Berman [31], Barker and Jarvo [32], and Lutter et al. [33].

Scheme 1.23 Pd‐catalyzed aromatic C–H amination via electrophilic amination.

      Source: Modified from Yoo et al. [34].

Scheme 1.24 Pd‐catalyzed aliphatic C–H amination via electrophilic amination.

      Source: Modified from He et al. [35].

Scheme 1.25 Ru‐catalyzed C–H amination.

      Source: Modified from Shang et al. [36].

A unique Fe‐catalyzed reaction was reported by the Yang group in which styrenes undergo formal hydroamination to afford tertiary amines with Markovnikov regioselectivity [38]. In this case, an organoferrates initially formed from a Grignard reagent and the iron(II) catalyst. This organoferrate intermediate engages the styrene substrate to form a hydride complex, which hydrometallates the styrene double bond and subsequently undergoes electrophilic amination (Scheme 1.27).

Scheme 1.26 Pd‐catalyzed Catellani‐type C–H electrophilic amination.

      Source: Modified from Dong and Dong et al. [37].

1.4 Electrophilic Amination with Hydroxylamine‐derived Metallanitrenes

A nitrene is the nitrogen analog of a carbene, which is a six‐electron electron‐deficient species. Although it is formally uncharged and univalent, it can be considered to be an electrophile because of the unsatisfied octet. These highly reactive intermediates are involved in many chemical reactions, including electrophilic aminations [39–41].

      Nitrene intermediates can be generated from various precursors. Pioneering studies by Khan and Kwart in the 1960s showed that elemental copper can catalyze the decomposition of a sulfonyl azide, and the resulting reaction mixture can aminate cyclohexene and give aziridine as one of the products [42]. This result is consistent with the participation of metallanitrene intermediates. However, because of the instability and toxicity of organic azides,

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