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Metal Coordination Controlled and Bifunctional H-Bonded Catalysis in Stereoselective Intramolecular Aldol Cyclizations toward Carbocyclic Tertiary beta-Ketols

par Chen, Bin;Berger, Gilles ;Hanessian, Stephen
Référence European Journal of Organic Chemistry, 2017, 18, page (2631-2636)
Publication Publié, 2017-05

Article révisé par les pairs

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Résumé :

The principle of bifunctional catalysis is shown in the highly regio- and stereoselective intramolecular aldolization of 2-methyl-1,3-cyclopentanedione, C2-substituted with a methyl ethyl ketone group, to provide [3.2.1]-bicyclooctanol diones in the presence of catalytic amounts of either LiBr and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), or 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). Mechanistic investigations corroborated by DFT calculations show that LiBr engages in a bifunctional coordination of two carbonyl moieties and leads to the preorganization of the reactive enolate intermediate for a base-mediated intramolecular aldol cyclization. On the other hand, TBD catalysis of the triketone substrate proceeds through a bifunctional H-bonded mechanism to give the same aldol product as the major diastereomer. The LiBr and TBD-catalyzed highly stereocontrolled intramolecular aldol cyclizations can be extended to other di- and triketones to give carbocyclic and carbobicyclic products as single diastereomers.