Terminal Heck Vinylations of Chelating Vinyl Ethers

Authors

  • Alexander Stadler,

    1. Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden, Fax: (+46)-18-471-4474
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  • Henrik von Schenck,

    1. Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden, Fax: (+46)-18-471-4474
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  • Karl S. A. Vallin,

    1. Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden, Fax: (+46)-18-471-4474
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  • Mats Larhed,

    1. Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden, Fax: (+46)-18-471-4474
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  • Anders Hallberg

    1. Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala Biomedical Centre, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden, Fax: (+46)-18-471-4474
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Abstract

Terminal chelation-controlled Heck vinylations of electron-rich amino-functionalized vinyl ethers were performed with high regioselectivity furnishing moderate to good isolated yields of the corresponding 1-alkoxy-1,3-butadienes. DFT calculations support an amine-palladium(II) coordination strength reactivity/selectivity rationale, where the dimethylamino group was the preferred metal presenting functionality. Controlled microwave heating effectively accelerated these palladium-catalyzed reactions and full conversion could be achieved within 30 minutes. Subsequent Diels–Alder reactions with dimethyl acetylenedicarboxylate under microwave irradiation resulted exclusively in partly aromatized bi- and tricyclic compounds by elimination of the aminoalkoxy group. Thus, the selected dimethylamino auxiliary both controlled the regiochemistry in the palladium-catalyzed vinylation and was easily displaced in the aromatization process.

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