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DOI: 10.1055/s-0034-1379561
Enantioselective Synthesis of Pyrrolidinones and Dihydropyridinones
N-Heterocyclic Carbene Catalyzed Cyclocondensation of α,β-Unsaturated Carboxylic Acids: Enantioselective Synthesis of Pyrrolidinone and Dihydropyridinone Derivatives.
Angew. Chem. Int. Ed. 2014;
53: 11611-11615
Publication History
Publication Date:
18 November 2014 (online)
Significance
Reported is an NHC-catalyzed enantioselective [3+2] and [3+3] cyclocondensation of α,β-unsaturated carboxylic acids with α-amino ketones and alkyl(aryl) imines to afford pyrrolidinones and dihydropyridinones. The [3+2] cyclocondensation proceeds to deliver pyrrolidinones with moderate diastereoselectivity and high enantioselectivity. The [3+3] cyclocondensation with sulfamate- and sultam-derived cyclic imines typically proceeds with excellent enantioselectivity to provide polycyclic dihydropyridinones in good yields.
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Comment
α,β-Unsaturated acyl azoliums comprise an important class of reactive Michael acceptors. These intermediates are typically generated from α,β-unsaturated carboxylate derivatives (e.g., α,β-unsaturated esters and α-bromoenals) via NHC catalysis. In this report, the readily available α,β-unsaturated carboxylic acids are employed directly to generate the corresponding azoliums, which are then subjected to cyclocondensation. The proposed mechanistic pathway involves in situ conversion of an activated α,β-unsaturated carboxylic acid to an α,β-unsaturated acyl azolium catalyzed by a chiral NHC. Subsequent Michael addition of an α-amino ketone or imine followed by intramolecular lactamization furnishes the cycloadduct.
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