Asymmetric synthesis of drug-like spiro[chroman-3,3 '-indolin]-2 '-ones through aminal-catalysis

• Published in: Organic & biomolecular chemistry Vol. 12; no. 4; pp. 574 - 580
• Main Authors: Ramachary, Dhevalapally B., Prasad, M. Shiva, Laxmi, S. Vijaya, Madhavachary, R.
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 28.01.2014
• Subjects: Amines - chemistry; Catalysis; Chemistry; Chemistry, Organic; Indoles - chemical synthesis; Indoles - chemistry; Molecular Structure; Physical Sciences; Science & Technology; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry; Stereoisomerism; ALDOL; CYCLOADDITION; DIELS-ALDER; ALPHA-AMINATION; MICHAEL; CONSTRUCTION; X-RAY; ORGANOCATALYSIS; CASCADE; DIENAMINE CATALYSIS
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c3ob42100g

Asymmetric synthesis of drug-like functionalized spiro[chroman-3,3'-indolinl-2'-ones 5 containing three contiguous stereocenters with high diastereo- and enantioselectivities was achieved using the reflexive-Michael (r-M) reaction of unmodified hydroxyenals 1 with various (E)-3-alkylideneindolin-2-ones 2 in the presence of (R)-DPPOTMS/AcOH (R)-3/4b as a catalyst at room temperature. Chiral spiro[chroman-3,3'-indolin]-2'-ones 5 were transformed into the functionalized spiranes 7, 9, and 10 in good yields with high selectivity through Wittig. TCRA, acetal protection and reduction reactions, respectively. Supporting evidence for the reaction pathway through the formation of the important catalytic species of "aminals" was observed through NMR and ESI-HRMS analysis of an ongoing reaction between 1 and (R)-3 in CDCl3 and also shown by the structural requirement in hydroxyenals 1 to generate the "aminals" with (R)-3 through controlled experiments.