Regiocontrol via Electronics: Insights into a Ru‐Catalyzed, Cu‐Mediated Site‐Selective Alkylation of Isoquinolones via a C−C Bond Activation of Cyclopropanols
烷基化
化学
催化作用
组合化学
有机化学
作者
Neha Jha,Wentao Guo,Wang‐Yeuk Kong,Dean J. Tantillo,Manmohan Kapur
A site-selective C(3)/C(4)-alkylation of N-pyridylisoquinolones is achieved by employing C-C bond activation of cyclopropanols under Ru(II)-catalyzed/Cu(II)-mediated conditions. The regioisomeric ratios of the products follow directly from the electronic nature of the cyclopropanols and isoquinolones used, with electron-withdrawing groups yielding predominantly the C(3)-alkylated products, whereas the electron-donating groups primarily generate the C(4)-alkylated isomers. Density functional theory calculations and detailed mechanistic investigations suggest the simultaneous existence of the singlet and triplet pathways for the C(3)- and C(4)-product formation. Further transformations of the products evolve the utility of the methodology thereby yielding scaffolds of synthetic relevance.