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 undergo annulative amination with electrophilic aminating reagents under Cu catalysis. Miura and coworkers have developed conditions for the synthesis of aminated benzofurans and indoles (Scheme 1.17) [24]. The transformation is operationally simple and proceeds at room temperature. The mechanism was probed and the authors concluded that the most plausible pathway is a nonradical electrophilic amination of the heteroarylcuprate species in the C—N bond‐forming step.
Similar intramolecular reactions can also take place with substrates containing unactivated terminal alkenes. In 2015, the Wang group (Duke University) reported the copper‐catalyzed vicinal diamination of unactivated alkenes with hydroxylamines that is both regio‐ and stereoselective. The first iteration of this reaction takes place on unsaturated amides and gives 4‐amino‐2‐pyrrolidones as the products (Scheme 1.18) [25]. This transformation is considered to be the first metal‐catalyzed alkene 1,2‐diamination that enables the direct incorporation of an electron‐rich amino group.
In 2016, Wang and coworkers successfully expanded the substrate scope to include unsaturated carboxylic acids, which undergo amino‐lactonization under the reaction conditions (Scheme 1.19) [26]. The overall transformation allows the practitioner to access quickly and efficiently a wide range of amino‐substituted γ‐ and δ‐lactones as well as 1,2‐amino alcohol derivatives, which are of significant value in the synthesis of natural products and active pharmaceutical ingredients.
Scheme 1.18 Cu‐catalyzed electrophilic diamination.
Source: Modified from Shen and Wang [25].
An unusual case of ring‐opening amination of cyclopropanols has been reported by the Dai group [27]. In this reaction, a base‐initiated ring‐opening of cyclopropanol generates a carbanion nucleophile, which participates in the Cu‐catalyzed electrophilic amination and affords β‐aminoketones as products (Scheme 1.20). The catalytic cycle involves the oxidation of the Cu(I) complex to the corresponding Cu(III) species by the hydroxylamine reagent. Next, the Cu(III) intermediate promotes the ring‐opening of the cyclopropanol substrate and the resulting copper‐homoenolate undergoes reductive elimination to form the new C—N bond and to regenerate the catalytically active Cu(I) species. Overall, the transformation