Premium
Metal Coordination Controlled and Bifunctional H‐Bonded Catalysis in Stereoselective Intramolecular Aldol Cyclizations toward Carbocyclic Tertiary β‐Ketols
Author(s) -
Chen Bin,
Berger Gilles,
Hanessian Stephen
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201700437
Subject(s) - chemistry , bifunctional , aldol reaction , intramolecular force , diastereomer , stereoselectivity , stereochemistry , ketone , aldol condensation , catalysis , medicinal chemistry , organic chemistry
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.