Broadly Applicable Copper(I)-Catalyzed Alkyne Semihydrogenation and Hydrogenation of α,β-Unsaturated Amides Enabled by Bifunctional Iminopyridine Ligands

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

A highly active bifunctional catalyst consisting of a copper(I)/N-heterocyclic carbene complex and basic 2-iminopyridine subunit allows for copper hydride chemistry under low H2 pressure, achieving efficient catalysis reaching 1 bar (balloon pressure). The tolerates remarkable variety functional groups in catalytic alkyne semihydrogenations. Furthermore, this design gives rise to high reactivity that the hydrogenation α,β-unsaturated amides (a substrate class hitherto unreactive catalysis) at pressure first time. In manner, late-stage modification isotope labeling amides, common subunits biologically compounds, can be realized through using first-row transition metal based on abundant copper. Preliminary mechanistic experiments indicate operates via an iminopyridine-mediated proximity effect. We hypothesize coordination alcohol as proton source copper(I) facilitates overall reactions rapid proto-decupration step.

Language: Английский

A ligand-assisted proximity effect allows for H2-driven copper hy-dride chemistry under mild conditions

Published: Oct. 16, 2024

A bifunctional copper(I)/N-heterocyclic carbene complex bearing a highly basic 2-iminopyridine subunit effects variety of copper(I) hydride-based reductive transformations at low H2 pressure. The catalyst allows for the first time to employ only catalytic amounts alkoxide additive and is with highest reactivity towards re-ported so far. We can demonstrate that efficient alkyne semihydrogenations, conjugate reductions as well 1,2-reductions carbonyl compounds be carried out very new protocol circumvents need previously required high-pressure equipment. At same time, use iminopyridine-based ligand tolerance an unprecedented functional groups in realm copper(I)-catalyzed hydrogenations. possible working model featuring iminopyridine-mediated proximity effect coordinates key close reactive cop-per(I) center proposed account observed significant rise reactivity. Mechanistic studies directed support-ing this current hypothesis are presented.

Language: Английский

Design and Synthesis of Isatin‐1,2,3‐triazole Hybrids as Anticancer Agents

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(47)

Published: Dec. 1, 2024

Abstract Isatin, a chemically defined indole‐1 H ‐2,3‐dione, is widely considered desirable therapeutic fragment in the field of drug discovery. Similarly, 1,2,3‐triazole ring major pharmacophore system among nitrogen containing heterocycles. Molecular hybrids comprising isatin and acyl azides functions linked by triazole rings were synthesized tested for cytotoxic effects against sixty human cancer cell lines due to resistance with most currently utilized anticancer medicines. The 1,2,3‐triazole‐isatin (8a–8j) produced high yields exceptional purity via Huisgen's 1,3‐dipolar cycloaddition involving azide, 7a–7j , an Isatin‐based N ‐alkyne 3 presence water as principal solvent n ‐Bu‐OH DMF cosolvents. compounds 8c 8g 8h showed highly effective growth inhibition breast, leukemia, melanoma lines, mortality ranging from 6% 99% PGI = >70% majority instances. While 8a 8b weak moderate action all line few 8d 8f 8i, 8j shows low activity. A molecular docking study cyclin‐dependent kinase (CDK2) could provide insights into mechanistic basis antitumor

Language: Английский