Chiral Bicyclic Imidazole-Catalyzed Direct Enantioselective C -Acetylation of Indolones

Design, Synthesis, and Application of Chiral Bicyclic Imidazole Catalysts

“…ZhouM.ZouY.ZhangL.ZhangZ.ZhangW. Zhou, M. Zou, Y. Zhang, L. Zhang, Z. Zhang, W. 10.31635/ccschem.022.20220178220221 . Based on the “Bond Angle Control” strategy, direct enantioselective C -acetylation of indolones was developed by TIP catalysts bearing a relatively smaller bond angle.…”

“…Therefore, we designed a new chiral tertiary amine nucleophilic catalyst bearing a stereocontrol group at the ortho- position of the catalytic active site (Figure ). This catalyst possesses a planar bicyclic imidazole skeleton with a larger bond angle of 127° for TIP and even larger bond angle of 137° for DPI …”

“…Using the novel chiral nucleophilic organocatalyst TIP bearing a 5,6,7,8-tetrahydroimidazo­[1,2- a ]­pyridine skeleton developed by our group, the asymmetric synthesis of 3,3-disubstituted benzofuranones by the direct C -acylation of 3-substituted benzofuranones has been realized . Very recently, another application of TIP catalysts was reported by our group in the highly efficient direct enantioselective C -acylation of indolones . As mentioned before in the design of chiral bicyclic imidazole catalysts, a smaller bond angle affords better stereocontrol, therefore we conceived that TIP catalysts bearing a 6-membered piperidine ring can further improve the enantioselectivity in the C -acylation reaction compared with DPI catalysts bearing a 5-membered pyrroridine ring.…”

Enzyme-Catalyzed Dynamic Kinetic Resolution of 2-Formylbenzoic Acids for the Asymmetric Synthesis of Phthalidyl Esters and Related Prodrugs

“…Therefore, enantioenriched prodrugs can be, in theory, hydrolyzed either faster or slower by enzymes, leading to a higher degree of metabolism manipulation. In the past decade, a number of asymmetric phthalide syntheses using an organometallic complex, organocatalyst, , and enzyme catalysis − have been reported, with some of the phthalide products exhibiting remarkable biological properties. However, the synthesis of chiral prodrugs, phthalidyl esters included, has not drawn enough attention from both academia and industry, mainly due to the lack of mature methodology and high R&D costs. − …”

COAP/Pd-Catalyzed Linear Asymmetric Allylic Alkylation for Optically Active 3,3-Disubstituted Oxindole Derivatives with a Four-Carbon Amino Side Chain

“…In the past decades, a large number of elegant methods for the synthesis of 3,3-disubstituted oxindoles with a chiral quaternary center have been developed. − Specifically, 3,3-disubstituted indolin-2-one derivatives with an amino basic group are one type of important molecular structures with a spectrum of biological and pharmaceutical activity. − As exemplified by the structures in Figure , 3,3-disubstituted indolin-2-one structures I with the tryptamine side chains exhibit significant anti-inflammatory activity . The basic indolin-2-one derivative II with a three carbon linear side chain shows Ca 2+ channel blocking potency in IMR-32 cells .…”