摘要：Juntao Sun†, Thomas H. Tugwell‡, Mithun C. Madhusudhanan‡, Letian Xu†, Shenghua Yang†,Peng Liu‡*, andKeary M. Engle†*
转自：康龙化成
A General Platform for Cu(II)-Catalyzed Hydrofunctionalization of Unactivated Alkynes via π-Lewis Acid Activation
Juntao Sun†, Thomas H. Tugwell‡, Mithun C. Madhusudhanan‡, Letian Xu†, Shenghua Yang†, Peng Liu‡*, and Keary M. Engle†*
† Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, United States; ‡ Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania, 15260, United States
—Chem Rxiv, 2025, 10.26434/chemrxiv-2025-pmqhx
Recommended by Rui Jin _ MC5
KEY WORDS:Cu catalysis, stereoselective; hydrofunctionalization(反应类型), C(sp2)-H, C(sp2)-O, C(sp2)-N (成键类型),alkynes, carboxylic acids, acidic OH-nucleophiles, sulfonamides (原料), trisubstituted alkenes, enol ether, enamine, alkylidene β-lactam (产物),π-Lewis acid activation (其他)
ABSTRACT:A copper(II)-catalyzed stereodivergent hydrooxygenation of electronically unactivated alkynes with carboxylic acids is reported. Regioselectivity and kinetic reactivity are facilitated by a bidentate auxiliary, and syn- or anti-stereoselectivity is controlled through judicial tuning of reaction conditions. The method affords trisubstituted E- or Z-alkenes with enol ester functionality in a highly selective manner. Beyond carboxylic acids, a variety of other OH- and NH-nucleophiles react smoothly to furnish enol ether, enamine and alkylidene β-lactam building blocks. Mechanistic experiments and density functional theory (DFT) calculations shed light on the nature of π-Lewis acid activation with Cu(II) and support a catalytic cycle that features inner-sphere nucleocupration mechanism via 6-membered transition state for syn-addition and base-assisted outer-sphere nucleocupration mechanism for anti-addition.
Background and this work
Condition screening
Substrate scope of carboxylic acids
Substrate scope of alkynes
Substrate scope: OH- and NH-nucleophiles
Applications: Gram-scale experiments and product transformations
In conclusion, Prof. Keary M. Engle and Prof. Peng Liu et al developa versatile platform employing Cu(II) as π-Lewis acid to achieve of electronically unactivated alkynes with diverse OH- and NH-nucleophiles. Regioselectivity and kinetic reactivity are facilitated by a bidentate auxiliary, and syn- or anti-stereoselectivity of benzoic acid coupling partners is controlled through judicious tuning of reaction conditions. An alkyne substrate bearing amono-dentateamidealsoexhibitsreactivityundera more forcing condition. Mechanistic experiments and DFT calculationssupportaninner-spherenucleometallation mechanism via a 6-membered transition state in syn-addition and highlightthe essential roles of DIPEA and DMA in the anti-addition pathway. We anticipate that this Cu(II)-catalyzed π-activation strategy can generalized to other π-bond containing substrates, providing a sustainable alternative to precious metal catalysts.
Scripps研究所Engle课题组和匹兹堡大学刘鹏课题组共同开发了一个以Cu(II)作为π-路易斯酸的多功能催化平台，成功实现了非活化炔烃与各类OH/NH亲核试剂的区域选择性和立体选择性偶联。通过双齿导向基团的辅助作用实现区域选择性和动力学控制，并借助反应条件的精准调控分别获得苯甲酸偶联的顺式或反式立体选择性产物。研究还发现，含单齿酰胺基团的炔烃底物在更剧烈条件下同样表现出反应活性。机理实验与DFT计算共同证实：顺式加成通过六元环过渡态的内球型金属亲核机制进行，而反式加成路径中DIPEA和DMA溶剂起着关键作用。预期这种Cu(II)催化的π-键活化策略可拓展至其他含π-键底物，为贵金属催化剂提供可持续的替代方案。
来源：新浪财经
