Remote and Proximal Hydroaminoalkylation of Alkenes Enabled by Photoredox/Nickel Dual Catalysis

Abstract

A mild and site-selective hydroaminoalkylation of activated and unactivated alkenes via dual photoredox/Ni catalysis is developed. This dual catalytic strategy enables exclusive access to α-selective products, which is complementary to previously reported photocatalytic hydroaminoalkylation of activated alkenes that provides the β-selective products. The chain-walking of a Ni− H intermediate toward a carbonyl allows for the hydroaminoalkylation of unactivated alkenes at remote sp 3 C−H sites. This method tolerates a broad substrate scope of both amines and alkenes as well as providing a streamlined synthesis of value-added β-amino acid derivatives from readily available starting materials.

Nickel-Catalyzed Remote C(sp3)–N/O Bond Formation of Alkenes with Unactivated Amines and Alcohols

“…By analyzing the 1 H NMR spectra, the remote etherification product was obtained bearing a different ratio of deuterium on the aliphatic chain (Scheme c). Indeed, these results support that t BuI acts as the hydride donor in the remote functionalization process, , and the different ratio of deuterium also indicates that it is a reversible process of chain-walking on the aliphatic chain. In addition, another deuterium labeling experiment using (β,β- d 2 )- 1a and benzyl alcohol was carried out, which also provided the desired product 55 with a different ratio of deuterium on the aliphatic chain; this result further supported the reversible process of isomerization (Scheme d).…”

Nickel/Photoredox Dual-Catalyzed Regioselective Alkyl-Aminoalkylation of Alkenes

“…Based on the experimental results and our previous reports [41,42] , two plausible pathways were proposed (Figure 7). Reductive quenching of *IrIII (E 1/2 * III/II = +0.66 V vs SCE) [43] by α-silylamine (E 1/2 ox = +0.4~+0.8…”

“…A series of acyclic (33,34) and cyclic secondary alkyl bromides including carbocycles (35)(36)(37) heterocycles (38, 39) and bridged system (40) were reacted with good yields. Regarding tertiary alkyl bromides, both acyclic and cyclic tertiary alkyl bromides containing ester, ether, NTs group were successfully converted to the desired regioisomerically pure products (41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51). The reaction can scale up to 3 mmol without an obviously diminished yield (57% vs 64% for compound 41).…”

Three-component reductive conjugate addition/aldol tandem reaction enabled by nickel/photoredox dual catalysis

“…Based on the above mechanistic studies and our previous reports, 11 a plausible mechanism was proposed for this reductive conjugate addition/aldol tandem sequence ( Scheme 3 ). First, successive SET process between the photoexcited *Ir III ( E IV/*III 1/2 = −1.73 V vs. SCE) 15 and Ni II [ E 1/2 (Ni II /Ni 0 ) = −1.2 V vs. SCE] 16 generates Ni 0 and Ir IV .…”

“…However, most reported photo-redox-assisted reductive cross-couplings are limited to the two-component version 9 with few exceptions have been extended to the intermolecular three-component reaction of aryl and alkyl halides across alkenes. 10 Giving our longstanding interest in metallaphotoredox catalysis, 9 e ,11 we reported here a Ni/photoredox-catalysed three-component conjunctive cross-electrophile coupling of aryl halides with aldehydes and alkenes (Scheme 1b). We envisioned that the key to success of this tandem transformation is to identify a suitable organic reductant as any organic reductants release protons might be problematic because they can protonate each tentative C–Ni bond species, thus producing unwanted outcomes such as a dehalogenation product and reductive Heck product.…”