The reactions at the C-3 carbonyl group of isatins, by nucleophilic addition or spiroannulation, transform them into 2-oxindole derivatives, featuring in a large number of natural and unnatural compounds with important biological activities.1 Going on with our interest in the asymmetric synthesis of 3,3-disubstituted oxindoles,2 we are developing a project aimed to explore the applicability of organocatalysis, particularly chiral Brønsted acid catalysis,3 to the enantioselective synthesis of quaternary 3-aminooxindole butenolides, through the vinylogous Mannich-type reaction of trimethylsilyloxyfuran and isatin-derived ketimines. The application of such reaction to ketimines remains to date largely unexplored,4 due to the steric challenge inherent in the stereocontrolled formation of a quaternary stereogenic center consecutive with a bulky tertiary one. Reaction of trimethylsilyloxyfurans with various preformed imines, derived from N-protected isatins and benzhydrylamine, allowed us to access a small family of highly functionalized diastereoisomeric compounds, in high yields and enantiomeric eccesses. To demonstrate the synthetic utility of the Mannich-type adducts, transformation reactions are presently in progress, in order to increase the number of potentially useful compounds. The assignment of the absolute and syn/anti relative configuration through X-ray diffraction is currently underway on selected compounds, as well as computational studies aimed to explain the stereochemical outcome of this organocatalyzed process. 1) 1. Singh, G.S.; Desta, Z.Y. Chem. Rev. 2012, 112, 6104. 2) Lesma, G.; Meneghetti, F. Belstein J. Org. Chem. 2014, 10, 1383. 3) Mahalau, M.; List, B. Angew. Chem. Int. Ed. 2013, 52, 518. 4) Bhaskara Rao V.U., Jadhav P.A., Org. Lett., 2014, 16, 648; Hermange P., Dodd R.H., Org. Lett., 2009, 11, 4044; Wieland L.C., Hoveyda A.H., J. Am. Chem. Soc., 2009, 131, 570; Hayashi M., Nakamura S., Angew. Chem. Int. Ed., 2013, 52, 5557; Shy Y.H., Wang Z., Tetrahedron, 2012, 68, 3649.

Enantioselective Organocatalyzed Vinylogous Mannich-Type Reaction Involving Isatin / G. Rainoldi, G. Lesma, A. Silvani, M. Stucchi. ((Intervento presentato al 36. convegno National Congress of Organic Chemistry Division (CDCO 2015) tenutosi a Bologna nel 2015.

Enantioselective Organocatalyzed Vinylogous Mannich-Type Reaction Involving Isatin

G. Rainoldi;G. Lesma;A. Silvani;M. Stucchi
2015-09-17

Abstract

The reactions at the C-3 carbonyl group of isatins, by nucleophilic addition or spiroannulation, transform them into 2-oxindole derivatives, featuring in a large number of natural and unnatural compounds with important biological activities.1 Going on with our interest in the asymmetric synthesis of 3,3-disubstituted oxindoles,2 we are developing a project aimed to explore the applicability of organocatalysis, particularly chiral Brønsted acid catalysis,3 to the enantioselective synthesis of quaternary 3-aminooxindole butenolides, through the vinylogous Mannich-type reaction of trimethylsilyloxyfuran and isatin-derived ketimines. The application of such reaction to ketimines remains to date largely unexplored,4 due to the steric challenge inherent in the stereocontrolled formation of a quaternary stereogenic center consecutive with a bulky tertiary one. Reaction of trimethylsilyloxyfurans with various preformed imines, derived from N-protected isatins and benzhydrylamine, allowed us to access a small family of highly functionalized diastereoisomeric compounds, in high yields and enantiomeric eccesses. To demonstrate the synthetic utility of the Mannich-type adducts, transformation reactions are presently in progress, in order to increase the number of potentially useful compounds. The assignment of the absolute and syn/anti relative configuration through X-ray diffraction is currently underway on selected compounds, as well as computational studies aimed to explain the stereochemical outcome of this organocatalyzed process. 1) 1. Singh, G.S.; Desta, Z.Y. Chem. Rev. 2012, 112, 6104. 2) Lesma, G.; Meneghetti, F. Belstein J. Org. Chem. 2014, 10, 1383. 3) Mahalau, M.; List, B. Angew. Chem. Int. Ed. 2013, 52, 518. 4) Bhaskara Rao V.U., Jadhav P.A., Org. Lett., 2014, 16, 648; Hermange P., Dodd R.H., Org. Lett., 2009, 11, 4044; Wieland L.C., Hoveyda A.H., J. Am. Chem. Soc., 2009, 131, 570; Hayashi M., Nakamura S., Angew. Chem. Int. Ed., 2013, 52, 5557; Shy Y.H., Wang Z., Tetrahedron, 2012, 68, 3649.
Settore CHIM/06 - Chimica Organica
Enantioselective Organocatalyzed Vinylogous Mannich-Type Reaction Involving Isatin / G. Rainoldi, G. Lesma, A. Silvani, M. Stucchi. ((Intervento presentato al 36. convegno National Congress of Organic Chemistry Division (CDCO 2015) tenutosi a Bologna nel 2015.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/470555
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