Lewis Acid Activated Synthesis of Highly Substituted Cyclopentanes by the N-Heterocyclic Carbene Catalyzed Addition of Homoenolate Equivalents to Unsaturated Ketoesters

Authors

  • Daniel T. Cohen,

    1. Department of Chemistry, Center for Molecular Innovation and Drug Discovery, Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208 (USA)
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  • Dr. Benoit Cardinal-David,

    1. Department of Chemistry, Center for Molecular Innovation and Drug Discovery, Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208 (USA)
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  • Prof. Karl A. Scheidt

    Corresponding author
    1. Department of Chemistry, Center for Molecular Innovation and Drug Discovery, Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208 (USA)
    • Department of Chemistry, Center for Molecular Innovation and Drug Discovery, Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208 (USA)
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  • Financial support was generously provided by the NIH (NIGMS RO1 GM73072), Amgen, AstraZeneca, GlaxoSmithKline, and a GAANN (Graduate Assistance in Areas of Nation Need) fellowship to D.T.C. FQRNT (Fonds Québécois de la Recherche sur la Nature et les Technologies) is also gratefully acknowledged for a postdoctoral fellowship to B.C.-D. We thank John M. Roberts (NU) for assistance with X-ray crystallography.

Abstract

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A great team: Cyclopentanes with four contiguous stereogenic centers were assembled with excellent diastereo- and enantioselectivity from simple β,γ-unsaturated α-ketoesters and enals in a reaction catalyzed by an N-heterocyclic carbene (NHC) and mediated by a titanium(IV) Lewis acid (see scheme). The presence of a Lewis acid was essential for the desired transformation to occur.

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