Enantioselective Organocatalytic Intramolecular Diels-Alder Reactions: A Computational Study

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Abstract

The diastereo- and enantioselectivity obtained experimentally by Christmann in the amine-catalyzed intra-molecular Diels-Alder reaction of alpha,beta-unsaturated carbonylic compounds were fully rationalized using density functional theory methods at the PBE1PBE/6-311+G** level. A polarizable continuum model was used to describe solvent effects. The selectivity is induced in the cyclization step, and while the enantioselectivity results from the syn/anti orientation around the C-N enamine bond, the diastereose-orientation around the C-N enamine bond, the diastereoselectivity mainly results from the syn/anti configuration of the substituents in the forming cyclopentane ring. The remarkable reaction rate experimentally observed when an external protic acid is used is attributed to the strong decrease in the activation energy of all steps needed for the enamine formation, while the external acid marginally influences the cyclization step. When hydrogen-bond-donor catalysts are used, the formation of one hydrogen bond in the cyclization step inverts the configuration and reduces the selectivity. The different behavior between dialdehydes and ketoaldehydes is suggested to be resulting from different reaction rates in the catalyst elimination step.
Original languageUnknown
Pages (from-to)3252-3261
JournalJournal of Organic Chemistry
Volume77
Issue numberNA
DOIs
Publication statusPublished - 1 Jan 2012

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