SYNTHESIS OF BENZOFURANONES VIA MALONATES DESYMMETRIZATION. S. Placidi,a A. Puglisi,a C. Giustini,a A. Ricucci,a E. Perrotti,a L. Massaro,a D. Morra,a F. Ciucci,a A. Zucchet,a A. Antenucci,a M. Moliterno,a R. Salvio,a,b M. Bellaa aDepartment of Chemistry, “Sapienza” University of Roma, P.le Aldo Moro 5, 00185 Roma; bIMC-CNR, Sezione Meccanismi di Reazione, P.le Aldo Moro 5, 00185 Roma; e-mail: simone.placidi@uniroma1.it Benzofuranones are interesting molecules due to their biological activity.1 Up today few studies have been conducted with respect to their synthesis compared to the corresponding oxindoles. The enantioselective synthesis of these compounds is currently carried out starting from pre-assembled benzofuranone moiety.2 In this work we present the synthesis of chiral, non-racemic benzofuranones, based on an asymetric intramolecular desymmetrization, catalyzed by Cinchona alkaloids and derivates, like quinine and catalyst I.3 Benzofuranones 4 are achieved by the addiction of malonates 1 to quinones 2 to give arylated achiral malonates 3 that subsequently undergo a cyclization reaction (Scheme1). Desymmetrization is an efficient metod for the synthesis of enantioenriched compounds starting from prochiral molecules.4 This approach allows to obtain products with high yields, up to 95%, and enantiomeric ratios as high as 97.5:2.5, in the best cases. Scheme 1. Synthesis of benzofuranones organocatalyzed by Cinchona alkaloids and proposed transition state leading to the major enantiomer (R). References 1. For examples see: a) K. M. Dawood, Expert Opin. Ther. Patents 2013, 23, 1133; b) C. Charrier, J. Clarhaut, J.-P. Gesson, G. Estiu, O. Wiest, J. Roche, P. Bertrand, J. Med. Chem. 2009, 52, 3112. 2. Y. Li, X. Li, J.-P. Cheng, Adv. Synth. Catal. 2014, 356, 1172. 3. A. Puglisi, C. Giustini, A. Ricucci, E. Perrotti, L. Massaro, D. Morra, F. Ciucci, A. Zucchet, A. Antenucci, M. Moliterno, S. Placidi, F. Sciubba, L. Galantini, R. Salvio, M. Bella, Chem. Eur. J. 2018, 24, 6945. 4. X. P. Zeng, Z. Y. Cao, Y. H. Wang, F. Zhou, J. Zhou, Chem. Rev. 2016, 116, 7330.
SYNTHESIS OF BENZOFURANONES VIA MALONATES DESYMMETRIZATION / Placidi, S.; Puglisi, a A.; Giustini, a C.; Ricucci, a A.; Perrotti, a E.; Massaro, a L.; Morra, a D.; Ciucci, a F.; Zucchet, a A.; Antenucci, a A.; Moliterno, a M.; Salvio, a R.; A, ; Bella, b M.. - (2018). (Intervento presentato al convegno International Summer School on Organic Synthesis "A.Corbella" - ISOS 2018 tenutosi a Gargnano sul Garda).
SYNTHESIS OF BENZOFURANONES VIA MALONATES DESYMMETRIZATION
S. Placidi;
2018
Abstract
SYNTHESIS OF BENZOFURANONES VIA MALONATES DESYMMETRIZATION. S. Placidi,a A. Puglisi,a C. Giustini,a A. Ricucci,a E. Perrotti,a L. Massaro,a D. Morra,a F. Ciucci,a A. Zucchet,a A. Antenucci,a M. Moliterno,a R. Salvio,a,b M. Bellaa aDepartment of Chemistry, “Sapienza” University of Roma, P.le Aldo Moro 5, 00185 Roma; bIMC-CNR, Sezione Meccanismi di Reazione, P.le Aldo Moro 5, 00185 Roma; e-mail: simone.placidi@uniroma1.it Benzofuranones are interesting molecules due to their biological activity.1 Up today few studies have been conducted with respect to their synthesis compared to the corresponding oxindoles. The enantioselective synthesis of these compounds is currently carried out starting from pre-assembled benzofuranone moiety.2 In this work we present the synthesis of chiral, non-racemic benzofuranones, based on an asymetric intramolecular desymmetrization, catalyzed by Cinchona alkaloids and derivates, like quinine and catalyst I.3 Benzofuranones 4 are achieved by the addiction of malonates 1 to quinones 2 to give arylated achiral malonates 3 that subsequently undergo a cyclization reaction (Scheme1). Desymmetrization is an efficient metod for the synthesis of enantioenriched compounds starting from prochiral molecules.4 This approach allows to obtain products with high yields, up to 95%, and enantiomeric ratios as high as 97.5:2.5, in the best cases. Scheme 1. Synthesis of benzofuranones organocatalyzed by Cinchona alkaloids and proposed transition state leading to the major enantiomer (R). References 1. For examples see: a) K. M. Dawood, Expert Opin. Ther. Patents 2013, 23, 1133; b) C. Charrier, J. Clarhaut, J.-P. Gesson, G. Estiu, O. Wiest, J. Roche, P. Bertrand, J. Med. Chem. 2009, 52, 3112. 2. Y. Li, X. Li, J.-P. Cheng, Adv. Synth. Catal. 2014, 356, 1172. 3. A. Puglisi, C. Giustini, A. Ricucci, E. Perrotti, L. Massaro, D. Morra, F. Ciucci, A. Zucchet, A. Antenucci, M. Moliterno, S. Placidi, F. Sciubba, L. Galantini, R. Salvio, M. Bella, Chem. Eur. J. 2018, 24, 6945. 4. X. P. Zeng, Z. Y. Cao, Y. H. Wang, F. Zhou, J. Zhou, Chem. Rev. 2016, 116, 7330.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
