Enantioselective organocatalytic intramolecular Diels-Alder reactions: a computational study

The Journal of Organic Chemistry
Filipe J S Duarte, A Gil Santos

Abstract

The diastereo- and enantioselectivity obtained experimentally by Christmann in the amine-catalyzed intramolecular Diels-Alder reaction of α,β-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 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.

References

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Citations

Jun 2, 2012·The Journal of Organic Chemistry·Miglena K GeorgievaA Gil Santos
Dec 11, 2014·Organic & Biomolecular Chemistry·Indresh KumarAnoop Singh
Nov 3, 2016·Chemical Society Reviews·Vanesa Marcos, José Alemán
Apr 20, 2013·Chemical Communications : Chem Comm·Igor D JurbergPaolo Melchiorre
Aug 16, 2013·Beilstein Journal of Organic Chemistry·Carsten S Kramer, Stefan Bräse
Aug 5, 2014·The Journal of Organic Chemistry·Snezhana M Bakalova, A Gil Santos

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