Asymmetric synthesis of 3-benzyl and allyl isoindolinones by Pd-catalyzed dicarbofunctionalization of 1, 1-disubstituted enamides. Issue 15 (1st June 2021)

• Record Type: Journal Article
• Authors: Huang, Wenyi; Shrestha, Mohini; Wang, Chenchen; Fang, Ke; Teng, Yaxin; Qu, Jingping; Chen, Yifeng
• Is Part Of: Organic chemistry frontiers. Volume 8:Issue 15(2021)
• Page Start: 4106
• Page End: 4111
• Publication Date: 2021-06-01
• Subjects: Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1039/d1qo00589h
• Languages: English
• ISSNs: 2052-4110

Abstract

Abstract : The Pd-catalyzed enantioselective Heck/Suzuki reaction of 1, 1-disubstituted enamides with aryl/vinyl boronic acids has been developed to access 3-benzyl/allyl substituted isoindolinones bearing a tetrasubstituted stereogenic carbon center. Abstract : Enantioenriched isoindolinones represent a valuable heterocycle motif, widely found in pharmaceuticals and biologically active natural products. We herein report a palladium-catalyzed asymmetric synthesis of 3, 3-disubstituted isoindolinones via the tandem Heck/Suzuki coupling of 1, 1-disubstituted enamides with aryl/alkenyl boronic acids under mild reaction conditions. This reaction exhibits both broad functional group tolerance and high enantioselectivity. We report the first dicarbo-functionalization of 1, 1-disubstituted enamides to generate amide derivatives bearing quaternary stereocenters. Finally, the synthetic utility of this protocol is demonstrated by the expedient synthesis of the PI3K-delta inhibitor precursor.