On Jul 6, 2020, the research group led by Prof. Yuan Weiming published a paper entitled "Selective 1,2-Aryl-aminoalkylation of Alkenes Enabled by Metallaphotoredox Catalysis" on Angewandte Chemie International Edition (ACIE, IF: 12.959). A highly chemo- and regioselective intermolecular 1,2-aryl-aminoalkylation of alkenes by photoredox/nickel dual catalysis is described in this paper. which provides an efficient and concise method for the synthesis of structurally valuable α-aryl substituted γ-amino acid derivatives motifs. The first author of this paper is the PhD student Zheng Songlin, and the co-authors include two undergraduates Liao Zixuan and Li Weirong from the School of Chemistry and Chemical Engineering. Huazhong University of Science and Technology is the only corresponding unit and Prof. Yuan Weiming is only corresponding author of this paper.
α-Aryl substituted γ-amino acid derivatives are unique structural motifs with biologically important actives in antagonists and pharmaceutical compounds. The traditional synthetic procedures1c-2 for α-aryl substituted γ-amino acid derivatives relied on multiple synthetic steps and the usage of either strong oxidants or reductants or highly reactive organometallic reagents, which suffered from relatively narrow functional group compatibility and low atom and step economy. Thus, developing more efficient and concise protocols towards to them are of high interest.
Representative biologically active compounds containing α-aryl substituted β-amino acid derivative motifs.
The merger of nickel and visible light photoredox catalysis could enable common sp3-hybridized C-nucleophiles instead of highly reactive organometallic reagents to participate the unprecedented C-C bond formations. The excited state of visible light photocatalysts are potent single-electron oxidants, which can readily undergo reductive quenching via single-electron-transfer (SET) oxidation of various Csp-nucleophilies to the corresponding alkyl radicals. This novel synergistic catalytic strategy provides a powerful potential to explore three-component conjunctive cross-coupling of π-bond systems with sp3-hybridized C-nucleophiles. In this aspect, Chu, Nevado, Molander and Aggarwal group have recently reported elegant examples of three-component conjunctive cross-coupling of alkenes with aryl halides and alkyl radical precursors. However, the regioselectivity is completely reversed due to the initial step arising from radical addition of C-nucleophile site, which is complementary to single metal catalyzed processes.
Recently, the research group led by Prof. Yuan Weiming developed a dual photoredox/nickel-catalyzed conjunctive cross-coupling of electron-deficient alkenes with α-silyl amines and aryl halides. This three-component reaction displayed very broad substrate scope and good functional group compatibility. Acrylates, acrylonitrile as well as α, β-unsaturated ketone and acrylamide were readily incorporated in this three-component conjunctive cross-coupling. Additionally, aryl halides including both iodides and bromides were compatible. This protocol benefits from its good selectivity, mild, base-free and redox-neutral conditions, and it is further characterized by the unprecedented tolerance of primary alkyl radicals, which were reluctant to cooperate in previous reports. The developed dicarbofunctionalization (DCF) process allows a rapid buildup of molecular complexity, especially provides an efficient and concise synthetic way for α-aryl substituted γ-amino acid derivatives.
Primary alkyl radical triggered olefin1,2-dicarbofunctionalization
The research group developed a dual photoredox/nickel‐catalyzed conjunctive cross‐coupling of electron‐deficient alkenes with α‐silyl amines and aryl halides, which provides an efficient and concise synthetic way for α-aryl substituted γ‐amino acid derivatives. This method is expected to play an important role in the synthesis of some antagonists and drug molecules.
Link of the paper: https://doi.org/10.1002/anie.202006439
