Diastereo- and Enantioselective Construction of a Bispirooxindole Scaffold Containing a Tetrahydro-β-carboline Moiety through an Organocatalytic Asymmetric Cascade Reaction

• Published in: Chemistry : a European journal Vol. 20; no. 36; pp. 11382 - 11389
• Main Authors: Dai, Wei, Lu, Han, Li, Xin, Shi, Feng, Tu, Shu-Jiang
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.09.2014; WILEY‐VCH Verlag; Wiley
• Subjects: asymmetric synthesis; Asymmetry; bispirooxindoles; Carbolines - chemistry; Cascade chemical reactions; Cascades; Catalysis; Catalysts; Chemistry; Chemistry, Multidisciplinary; Construction; enantioselectivity; Indoles - chemical synthesis; Indoles - chemistry; Models, Molecular; multicomponent reactions; organocatalysis; Phosphoric Acids - chemistry; Physical Sciences; Scaffolds; Science & Technology; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry; Stereoisomerism; Stereoselectivity; enantioselectivity; multicomponent reactions; 1,3-DIPOLAR CYCLOADDITIONS; DIELS-ALDER REACTIONS; OXINDOLES; PICTET-SPENGLER REACTIONS; CONTIGUOUS STEREOCENTERS; HIGHLY EFFICIENT; organocatalysis; asymmetric synthesis; PHOSPHORIC-ACID; bispirooxindoles; CHIRAL BRONSTED ACID; SPIROCYCLOPENTANE BIOXINDOLES; DERIVATIVES
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.201402485

The first catalytic asymmetric construction of a new class of bispirooxindole scaffold‐containing tetrahydro‐β‐carboline moiety has been established through chiral phosphoric acid‐catalyzed three‐component cascade Michael/Pictet–Spengler reactions of isatin‐derived 3‐indolylmethanols, isatins, and amino‐ester, which afforded structurally complex and diverse bispirooxindoles with one quaternary and one tetrasubstituted stereogenic centers in excellent stereoselectivities (all >95:5 diastereomeric ratio (d.r.), up to 98:2 enantiomeric ratio (e.r.)). This intriguing class of chiral bispirooxindoles integrated the two important structures of tetrahydro‐β‐carboline and bispirooxindole, both of them possessing significant bioactivities. This approach also combined the merits of asymmetric organocatalysis and multicomponent tandem reaction, which provided a unique strategy for the preparation of structurally rigid bispiro‐architectures with concomitant creation of multiple quaternary stereogenic centers. First class construction: The first catalytic asymmetric construction of a new class of bispirooxindole scaffold containing a tetrahydro‐β‐carboline moiety has been established through chiral phosphoric acid catalyzed three‐component cascade Michael/Pictet–Spengler reactions of isatin‐derived 3‐indolylmethanols, isatins, and an amino ester, which afforded structurally complex and diverse bispirooxindoles with two stereogenic centers in excellent stereoselectivities (see scheme; BH*=chiral Brønsted acid, 1,1,2,2‐TCE=1,1,2,2‐tetrachloroethane; all >95:5 d.r., up to 98:2 e.r.).