Palladium-Catalyzed Decarbonylative Dehydration for the Synthesis of α-Vinyl Carbonyl Compounds and Total Synthesis of (−)-Aspewentins A, B, and C

Authors

  • Yiyang Liu,

    1. The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA)
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  • Dr. Scott C. Virgil,

    1. The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA)
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  • Prof. Robert H. Grubbs,

    Corresponding author
    1. The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA)
    • The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA)

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  • Prof. Brian M. Stoltz

    Corresponding author
    1. The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA)
    • The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA)

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  • We wish to thank the Resnick Sustainability Institute at Caltech (graduate fellowship to Y.L.), NIH (R01M080269 to B.M.S., 5R01M031332-27 to R.H.G.), the Gordon and Betty Moore Foundation, the Caltech Center for Catalysis and Chemical Synthesis, and Caltech for financial support. Dr. David VanderVelde is acknowledged for assistance with NMR spectroscopy. Dr. Mona Shahgholi and Naseem Torian are acknowledged for assistance with high-resolution mass spectrometry. We would like to thank Prof. Richmond Sarpong of UC Berkeley for helpful discussions.

Abstract

The direct α-vinylation of carbonyl compounds to form a quaternary stereocenter is a challenging transformation. It was discovered that δ-oxocarboxylic acids can serve as masked vinyl compounds and be unveiled by palladium-catalyzed decarbonylative dehydration. The carboxylic acids are readily available through enantioselective acrylate addition or asymmetric allylic alkylation. A variety of α-vinyl quaternary carbonyl compounds are obtained in good yields, and an application in the first enantioselective total synthesis of (−)-aspewentins A, B, and C is demonstrated.

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