Synthesis of Cycloalkanoindoles by an Unusual DAST-Triggered Rearrangement Reaction

• Published in: European journal of organic chemistry Vol. 2004; no. 11; pp. 2411 - 2420
• Main Authors: Giannini, Giuseppe, Marzi, Mauro, Moretti, Gian Piero, Penco, Sergio, Tinti, Maria Ornella, Pesci, Silvia, Lazzaro, Francesco, De Angelis, Francesco
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.06.2004; WILEY‐VCH Verlag; Wiley
• Subjects: Angiogenesis inhibitors; Chemistry; Chemistry, Organic; Cycloalkanoindole; Electrophilic annulation; Electrophilic substitution; Geminal bis(indolyl) compounds; Physical Sciences; Rearrangement; Science & Technology; cycloalkanoindole; geminal bis(indolyl) compounds; SERIES; INDOLE; ANALOG; TETRAHYDROCARBAZOLES; RECEPTOR; angiogenesis inhibitors; electrophilic annulation; electrophilic substitution; rearrangement
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200300738

A series of 1,1‐bis(indol‐3‐yl) and 1‐(indol‐2‐yl)‐1‐(indol‐3‐yl)‐ψ‐hydroxyalkanes, prepared from the corresponding indole derivatives and suitable hydroxyaldehydes via routine coupling reactions, were treated with DAST (diethylaminosulfur trifluoride) under mild conditions, to generate a small library of cycloalkanoindoles. Irrespective of the substitution pattern, i.e. whether they are symmetrical or unsymmetrical derivatives, the same mixture of products is produced, in which the tetrahydro‐1H‐carbazole and hexahydrocyclohepta[b]indole scaffolds are substituted by a indol‐3‐yl nucleus on one of the two α‐carbon atoms of the cycloalkane moieties. Thus, speculations on the reaction mechanism with the prediction of a common reaction intermediate are presented. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)