Nickel-Catalyzed Asymmetric Synthesis of β- or β,γ-Substituted GABA Derivatives Enabled by Photoactive Ternary Electron Donor–Acceptor Complex

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(24), P. 18734 - 18743

Published: Dec. 10, 2024

Enantiopure γ-amino butyric acids (GABA) and derivatives have important applications in medicinal chemistry, especially for the treatment of central nervous system diseases. Many marketed drugs feature this moiety. In context, we developed a highly enantioselective catalytic strategy rapidly forging β- or β,γ-substituted GABA by exploiting an unexplored ternary electron donor–acceptor (EDA) complex simultaneously driven visible light chiral Ni catalyst. With cooperative system, range structurally diverse been achieved high yields with good enantio- diastereoselectivities (up to 88% yield, >99% ee, >19:1 dr). Mechanistic studies indicate that key success is dual role catalyst, which not only promotes formation EDA complexes generated from redox-active esters, Hantzsch catalyst but can also precisely provide asymmetric induction. The synthetic benefits method were proved enabling easy access pharmaceuticals related bioactive molecules such as pregabalin, baclofen, rolipram, phenibut.

Language: Английский

Mechanistic Insights into Enantioselective C(sp³)−H Acylation to Construct α‐Amino Ketones via Photoredox and Ni(II) Dual Catalysis: A DFT Study

Chemistry - An Asian Journal, Journal Year: 2023, Volume and Issue: 18(8)

Published: March 5, 2023

The development of the merger a Ni(II) catalyst with an appropriate photocatalyst under visible-light irradiation provides new strategy for realizing direct functionalization C(sp3 )-H bonds. Mechanistically, whether reduction Ni to form Ni(0) species is necessary in dual catalysis still remains debate. Herein, DFT calculations were carried out gain mechanistic insight into enantioselective acylation α-amino bonds furnish ketones via photoredox and catalysis. A feasible pathway Ni(I)-Ni(III)-Ni(II)-Ni(III)-Ni(I) cycle suggested sequential elementary steps oxidative addition, single electron reduction, radical reductive elimination leading final product, whereas nickel catalytic cycle, Ni(I)-Ni(0)-Ni(II)-Ni(III)-Ni(I), might not be dual-catalyzed origin stereoselectivity this reaction also discussed, which could attributed minimization steric hindrance between alkyl moiety part phenyl group chiral ligand.

Language: Английский