Proline bulky substituents consecutively act as steric hindrances and directing groups in a Michael/Conia-ene cascade reaction under synergistic catalysis

• DOI: 10.1039/c8sc05258a
• Publication Date: 2019-03-04T12:34:21Z
• Authors: Salil Putatunda; Juan V. Alegre-Re...; Marta Meazza; Michael Franc; Dominika Rohal'ová; Pooja Vemuri; Ivana Císařová; Raquel P. Herrera; Ramon Rios; Jan Veselý
• Keywords: Ene reaction; Michael reaction

In this study, we report a highly stereoselective and versatile synthesis of spiro pyrazolones, promising motifs that are being employed as pharmacophores. The new synthetic strategy merges organocatalysis metal catalysis to create synergistic using proline derivatives Pd catalysts. This protocol is suitable for late-stage functionalization, which very important in drug discovery. Additionally, thorough computational study proved be useful elucidate the function different catalysts along reaction, showing peculiar feature: -CPh2OSiMe3 group catalyst switches its role during reaction. initial Michael plays commonly-assumed bulky blocking group, but same generates π-Pd interactions acts directing subsequent Pd-catalyzed Conia-ene finding might relevant especially processes with many steps, such cascade reactions, functional groups assumed play all reaction steps.