Kinetic and Theoretical Studies of a Facile, One-Pot Preparation of a Spirocyclohexylindolinone Derivative

• Published in: European Journal of Organic Chemistry Vol. 2006; no. 7; pp. 1769 - 1778
• Main Authors: Sánta-Csutor, Andrea, Mucsi, Zoltán, Finta, Zoltán, Gönczi, Csaba, Halász, Judit, Csikós, Éva, Hermecz, István
• Format: Book Review Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.04.2006; WILEY‐VCH Verlag; Wiley
• Subjects: Chemistry; Chemistry, Organic; Density functional calculations; Kinetics; Michael addition; Physical Sciences; Reaction mechanisms; Science & Technology; Spiro compounds; Michael addition; density functional calculations; INDOL-2(3H)-ONE; reaction mechanisms; OXINDOLES; VASOPRESSIN V-2; HIGHLY POTENT; kinetics; spiro compounds; V-2 RECEPTOR ANTAGONIST
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200500798

Spirocyclohexylindolinone is used as a moiety in drug substances. A number of synthetic methods have been suggested to introduce the cyclohexyl ring into the C(3) position of N‐protected indolinones, which complicates their preparation. A previously developed, consecutive, one‐pot, multicomponent method is studied from a mechanistic aspect. We set out to clarify the details of this mechanism and the role of the acryl ester as a reagent and a protecting group in the same flask, by using theoretical and analytical methods, in order to optimise the preparative conditions. A mechanistic energy profile of the reaction is computed at the DFT level of theory. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)