Synthesis of N-Heterocycles from Donor Acceptor Cyclopropanes and Progress towards Flinderole A, B, and C

The first chapter of this thesis describes two projects, one explores the novel reactivity of quaternary donor acceptor cyclopropanes and the second one involves progress toward the total synthesis of the flinderoles A, B, and C. The first project involves the Lewis acid catalyzed nucleophilic ring opening of quaternary donor acceptor cyclopropanes with indoline. It was found that the ring opening reaction worked well with either Sc(OTf)3 or Yb(OTf)3 as the Lewis acids. The ring opened products were also able to be converted into pyrroloindoles via a manganese (III) oxidative radical cyclization reaction. Cyclopropanes bearing alkynyl, vinyl, and aryl substituents were well tolerated as well as indolines bearing substitution at the 3-position. The second project involves the application of the ring opening/cyclization reaction to synthesize the pyrroloindole scaffold of the flinderoles. The chapter also describes our efforts to complete the synthesis of the natural products, and despite many alternative routes, we were not able to access the flinderoles. The second chapter describes the Lewis acid catalyzed annulation reactions of donor acceptor cyclopropanes with vinyl azide and 2H-azirine. Surprisingly, the reaction with either the vinyl azide or 2H-azirine gave the same azabicyclic product. The reaction was also limited to cyclopropanes bearing trifluoroethyl esters instead of the common methyl esters. The reaction scope with respect to the cyclopropanes tolerated aryl, heteroaryl, vinyl, alkynyl and quaternary substituents on the cyclopropane. In both reactions, the azabicycle was obtained as a single diastereomer, which was confirmed by x-ray crystallography

Radical Cyclizations for the Synthesis of Pyrroloindoles: Progress toward the Flinderoles

Under the influence of Lewis acid catalysis, donor/acceptor cyclopropanes underwent nucleophilic ring opening by indolines. The resulting <i>N</i>-alkyl indolines bearing a pendant malonyl moiety oxidatively cyclized to 1,2-pyrroloindoles. This method was showcased by the preparation of the skeletal structure of the flinderoles

Annulation Reactions of Donor–Acceptor Cyclopropanes with (1-Azidovinyl)benzene and 3‑Phenyl‑2<i>H</i>‑azirine

Under the influence of heat and Lewis acid, donor/acceptor cyclopropanes underwent annulation reactions with (1-azidovinyl)­benzene and 3-phenyl-2<i>H</i>-azirine to form an unusual azabicyclic scaffold with an imbedded aziridine. The mechanism of reaction is believed to proceed via a vinyl nitrene intermediate