Metal Coordination Controlled and Bifunctional H‐Bonded Catalysis in Stereoselective Intramolecular Aldol Cyclizations toward Carbocyclic Tertiary β‐Ketols. Issue 18 (12th May 2017)

• Record Type: Journal Article
• Authors: Chen, Bin; Berger, Gilles; Hanessian, Stephen
• Is Part Of: European journal of organic chemistry. Issue 18(2013)
• Page Start: 2631
• Page End: 2636
• Publication Date: 2017-05-12
• Subjects: Organocatalysis -- Aldol reactions -- Bifunctional catalysis -- Density functional calculations -- β‐Ketol; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201700437
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : 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. Abstract : Oxophilic LiBr/1, 8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) or 1, 5, 7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD) are excellent catalysts for activating carbonyl groups of 1, 5‐diketones to generate energetically favored Li and H‐bonded intermediates. In these, a carbonyl group and an enol(ate) are exquisitely aligned to give conformationally and stereochemically distinct β‐ketols in an intramolecular aldolization.