1.8) [15]. The hygroscopic nature of O‐benzyl hydroxylamine necessitates its use as a stock solution in an organic solvent.
The instability of organometallic reagents used in the aforementioned reactions imposes limits on their widespread utilization, especially in an industrial setting. Efforts have been made to replace the air‐ and moisture‐sensitive organometallic reagents with more stable alternatives that can be conveniently stored and used. Miura and coworkers (Osaka University, Japan) have shown that both arylboronates (Scheme 1.9) [16] and arylsilanes (Scheme 1.10) [17] can serve as starting materials in Cu‐catalyzed electrophilic amination reactions. These reactions can proceed under ambient temperature and furnish the corresponding anilines in good to excellent isolated yields. The enhanced stability of arylboronates and arylsilanes reduces the complexity of the operation and, at the same time, the wide commercial availability of arylboronates also adds convenience to these types of reactions.
Scheme 1.8 Electrophilic amination via directed C–H cupration.
Scheme 1.9 Cu‐catalyzed electrophilic amination of arylboronates.
Hirano and Miura discovered that ambident nucleophiles such as silyl ketene acetals are also suitable nucleophiles for the Cu‐catalyzed electrophilic amination reactions. These reactions result in the formation of alpha‐amino esters as products. The first generation of this reaction uses chloramines as aminating reagents [18], while the second generation can proceed with the more stable and much safer O‐benzoyl hydroxylamines (Scheme 1.11) [19]. This method provides a potential route for the syntheses of unnatural as well as modified natural amino acids.
Scheme 1.10 Cu‐catalyzed electrophilic amination of aryl silanes.
Source: Modified from Miki et al. [17].
Weak nucleophiles such as styrenes and some electron‐deficient heterocycles can also participate in Cu‐catalyzed electrophilic amination reactions.
In the case of styrenes, the substrates can undergo hydroamination or aminoboration depending on the specific reaction conditions. Hirano, Miura, and coworkers have demonstrated that styrenes can be stereoselectively functionalized with benzoyl hydroxylamine and bis(pinacolato)diboron under Cu catalysis (Scheme 1.12) [20]. The resulting products can further participate in transition‐metal‐catalyzed cross‐coupling reactions.
When polymethylhydrosiloxane (PMHS) is used instead of bis(pinacolato)diboron, hydroamination products can be obtained under similar reaction conditions (Scheme 1.13). In these cases, it is proposed that the reaction proceeds with an initial CuH addition across the C—C bond of the olefins, followed by the electrophilic amination of the resulting cuprates [21].
With chiral ligands, the hydroamination reactions can give enantiomerically enriched products. Both the Miura (Scheme 1.14) and Buchwald (Scheme 1.15) groups have developed conditions using chiral phosphine ligands [21, 22].
Buchwald and coworkers have also reported the hydroamination of aryl acetylenes. The reaction is highly stereoselective, giving E‐enamines as the major products. The enamine products can be further reduced to give alkyl amines, which are important building blocks in organic synthesis (Scheme 1.16) [23].
Scheme 1.11 Cu‐catalyzed electrophilic amination of silyl enol ethers.
Source: Modified from Matsuda et al. [19].
Scheme 1.12 Cu‐catalyzed electrophilic catalyzed aminoboration of styrenes.
Source: Modified from Matsuda et al. [20].
Scheme 1.13 Cu‐catalyzed electrophilic hydroamination of styrenes.
Source: Modified from Miki et al. [21].
Scheme 1.14 Enantioselective Cu‐catalyzed electrophilic hydroamination of styrenes.
Source: Miki et al. [21].
Scheme 1.15 Enantioselective Cu‐catalyzed electrophilic hydroamination of styrenes.
Source: Modified from Zhu et al. [22].
Scheme 1.16 Cu‐catalyzed electrophilic amination of alkynes.
Source: Shi and Buchwald [23].
Scheme 1.17 Cu‐catalyzed annulative electrophilic amination.
Source: Modified from Matsuda et al. [24].
ortho‐Alkynyl phenols and anilines can also
