Vinylselenoxide and vinylsulfoxide directed lactonization: Syntheses of pyrroloindolenine alkaloids and optically active aflatoxin B1 precursor.

Abstract

The reaction between a vinylsulfoxide and a ketene produces a $\gamma$-butyrolactone, and it is believed that this process includes a (3,3) sigmatropic rearrangement. In this thesis research, the generality and the wide applicability of the vinylsulfoxide directed lactonization reaction is shown. When chlorocyanoketene reacted with various vinylsulfoxides, the corresponding $\gamma$-butyrolactones were generated in modest to excellent yields. Chlorocyanoketene is the first ketene which does not require any base or metal in its generation and which can be successfully used in the lactonization process. Chlorocyanoketene was also reacted with vinylselenoxides to provide the $\gamma$-phenylselenenyl-$\gamma$-butyrolactones in modest yields. Stable ketenes such as $t$-butylcyanoketene, diphenylketene, and the trimethylsilylketene, were determined to be unreactive in the lactonization process due to steric and/or electronic effects. Reactivities of heteroaromatic sulfoxides were examined under the lactonization reaction conditions. While the furan, benzofuran, and benzothiophene rings were determined too aromatic to undergo the desired transformation, 2- and 3-alkylsulfinylindoles were converted to the corresponding indolenine-fused furanones via the lactonization reaction. The furanone prepared from $N$-benzenesulfonyl-2-methanesulfinylindole was transformed to the corresponding 8-benzenesulfonyl-2,3a-dimethyl-2-oxo-3,3a,8,8a-tetrahydropyrrolo(2,3-b) indole, an obvious precursor of medicinally important physostigmine alkaloids. Finally, the aflatoxin B1 precursor 4-hydroxy-6-methoxy-3,3a,8,8a-tetrahydrofuro(2,3-b) benzofuran-2-one was prepared in an optically active form in a modest e.e. (60%) via the sulfoxide directed lactonization methodology followed by an intramolecular displacement of the incipient $\gamma$-arylthio moiety. This new methodology for the preparation of the furo(2,3-b) benzofuran-2-ones provides a general route for the preparation of mycotoxins which bear furobenzofuran unit. A new method for the preparation of $\beta$-arylvinylsulfoxides which utilizes the coupling of an aryl iodide and $\beta$-tributylstannyl vinyl sulfoxide was developed.