Asymmetric synthesis of drug-like spiro[chroman-3,3′-indolin]-2′-ones through aminal-catalysisElectronic supplementary information (ESI) available: Experimental procedures and analytical data (1H NMR, 13C NMR, HRMS and HPLC) for all new compounds. CCDC 937954. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3ob42100g

• Main Authors: Ramachary, Dhevalapally B, Shiva Prasad, M, Vijaya Laxmi, S, Madhavachary, R
• Format: Journal Article
• Language: English
• Published: 18.12.2013
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c3ob42100g

Asymmetric synthesis of drug-like functionalized spiro[chroman-3,3′-indolin]-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 CDCl 3 and also shown by the structural requirement in hydroxyenals 1 to generate the " aminals " with ( R )- 3 through controlled experiments. An interesting reflexive -Michael ( r -M) reaction has been developed to access drug-like spiro[chroman-3,3′-indolin]-2′-ones in good yields with excellent ee's and de's using aminal -catalysis.