Enantioselective 1,3-Dipolar Cycloaddition Reactions of C -Carboxy Ketonitrones and Enals with MacMillan Catalysts: Evidence of a Nonconcerted Mechanism

Autor: Souhir Abid, Arnaud Martel, Mathieu Y. Laurent, Gilles Dujardin, Khalid B. Selim, Kawther Ben Ayed
Rok vydání: 2017
Předmět:
Zdroj: European Journal of Organic Chemistry. 2017:6763-6774
ISSN: 1434-193X
DOI: 10.1002/ejoc.201701307
Popis: Highly diastereo- and enantioselective 1,3-dipolar cycloadditions between functional ketonitrones and β-substituted enals are promoted by organocatalysis with the imidazolidinium catalyst of MacMillan. Study of the scope of the reaction shows that high selectivities are conserved by varying the N-protecting group or the ester function. However it is sensitive to sterical interaction with the C-substituent of the nitrone. Reaction proceeds in all cases with a high exo selectivity. In most cases, a third diastereomer, not compatible with a concerted mechanism, was observed, although in minute amount. DFT calculations evidence that the cycloaddition proceeds in a non-concerted fashion by a first oxa Michael-type addition of the nitrone to the double bond followed by a cyclization. This mechanism explains the formation of the observed minor diastereomers. In addition, the diastereo- and enantioselectivities of the reaction were shown to be intermediately thermodynamically controlled and the diastereomeric ratio is modulated by the kinetics of iminium hydrolysis.
Databáze: OpenAIRE
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