The Type 2 Intramolecular Diels-Alder Reaction

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The Type 2 Intramolecular Diels-Alder Reaction. Tether is attached to the 1 position of the diene Leads to fused bicycles. Tether is attached to the 2 position of the diene Leads to bridged bicycles with bridgehead double bonds Tether can control regioselectivity, stereoselectivity, and - PowerPoint PPT Presentation

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  • The Type 2 Intramolecular Diels-Alder Reaction

    Tether is attached to the 1 position of the diene Leads to fused bicycles Tether is attached to the 2 position of the diene Leads to bridged bicycles with bridgehead double bonds Tether can control regioselectivity, stereoselectivity, and

    p-facial selectivity

  • Hetero Type 2 Diels-Alder Reactions

    Previous work in the area of hetero type 2 Diels-Alder reactions has shown N-acyl

    imines to participate in the Diels-Alder reaction to provide bridgehead amides.1

    Current studies are looking to expand the scope of the type 2 hetero intramolecular

    Diels-Alder reactions.

    The use of a more reactive hetero dienophile is being investigated.
  • Type 2 Intramolecular Nitroso Diels-Alder Reactions

    The type two intramolecular Diels-Alder cycloaddition of N-acylnitroso dienophiles

    is currently being studied for the synthesis of bridged [n,3,1] oxazinolactams.

    In situ oxidation of hydroxamic acids provide N-acyl nitroso dienophiles which

    undergo cycloaddition to provide 3,6 dihydro-1,2 oxazines.

    These cycloadducts can subsequently be transformed into medium ring amides

    and amines.

  • Synthesis of Precursor Hydroxamic Acids

  • Synthesis of Bridged [n,3,1] Oxazinolactams

  • 9, 10-Dimethylanthracene Adducts

  • Regiochemistry of T2IMNDA

  • Measuring Bridgehead Olefin Distortion

    Two parameters, and , are used to quantify the degree of distortion in a strained olefin.2 , which represents the angle between the p-orbitals of a bond, is measured by

    = (1 + 2)/2 shown in composite structure V.

    , the pyramidalization angle of the constituent atoms of the system, is defined as the

    acute angle formed by the projection of one substituent (Z) across the atom onto the

    geminal substituent (Y). For an sp2.00 atom, = 0.0, while for an sp3.00 atom, =60.0.

  • X-Ray Crystal Structures

    4 5

    Parameter 4 5

    tC4-C56.83(9)3.53(9)

    cC520.313.5

    tN1-C93.53(9)

    tN1-C1010.35(8)

    cC90.4

    cC101.5

    cN154.852.6

    531.psd
  • Functionalization of Bridged Oxazinolactams

  • Work in Progress

  • References and Acknowledgements

    1. The Type 2 Intramolecular Imino Diels-Alder Reaction. Synthesis and Structural Characterization

    Of Bicyclo [n,3,1] Bridgehead Olefin/Bridgehead Lactams. Shea, K.J., Lease, T.G.: J. Am. Chem.

    Soc. 1993, 115, 2248

    2. Winkler, F. K.: Dunitz, J. D. J. Mol. Biol. 1971, 59, 169-182.

    Financial Support of this work from the Undergraduate Research Opportunities Program is

    gratefully acknowledged.

    Financial Support of this work from Allergan is gratefully acknowledged. Travel Funding from the UCI CAMP program is gratefully acknowledged.