Applications of Electron Transfer Initiated Cyclizations

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The purpose of this proposal is to continue the development of the electron transfer initiated cyclization reaction and to use this methodology for the synthesis of biologically important structures. In this reaction the photoinitiated single electron oxidation of alkylarenes substituted at the homobenzylic position with an electron donating substituent produces radical cations containing substantially weakened and polarized benzylic carbon-carbon bonds. Appended nucleophiles, such as hydroxyl, ether, and amide groups can displace benzylic radicals, resulting in a cyclization reaction. The mild reaction conditions and unique chemoselectivity exhibited by single electron transfer make this reaction a potentially very powerful new method for constructing organic molecules. Specific goals for the project include: A thorough study of the types of cation stabilizing substituents, aromatic leaving groups, and nucleophiles tolerated by this reaction. This study includes the development of new heterogenerative cascade reactions. The development of a chemically initiated variant of the reaction. The development of an electron transfer initiated cyclorelease reaction from a polymer support. Employment of the reaction as the key step in brief total syntheses of potent antitumor and immunosuppressant agents from the pederin and mycalamide family, and the use of these sequences in the synthesis of analogs. The proposed program provides both new methodology for organic synthesis and efficient routes to challenging and medicinally important structures.