Date of Graduation

2017

Document Type

Dissertation

Degree Type

PhD

College

Eberly College of Arts and Sciences

Department

Chemistry

Committee Chair

Bjorn C G Soderberg

Committee Co-Chair

Jessica M Hoover

Committee Member

Mark L McLaughlin

Committee Member

Brian V Popp

Committee Member

Kung K Wang

Abstract

Total syntheses of the three naturally occurring indole alkaloids alocasin A, scalaridine A and hyrtinadine A-B have been accomplished using three palladium catalyzed reactions, an alkyne hydrostannylation, a Kosugi-Migita-Stille coupling and a reductive N-heterocyclization as the key steps. A palladium catalyzed double reductive cyclization of 1,4-, 1,3-, and 2,3-bis(2-nitroaryl)-1,3-butadienes to afford 2,2'-, 2,3'-, and 3,3'-biindoles, respectively, has been developed. In an attempt to synthesize indolo[2,3-b]-and indolo[3,2-b]-indoles from the reductive cyclizations of 1,1'-, and 1,2'-bis(2-nitroaryl)ethenes respectively, nonselective product formation was observed giving rise to carbon monoxide insertion product as the sole or the major reaction product. The reductive cyclization strategy was extended to achieve the expedient synthesis of three naturally occurring polybrominated biindoles; 2,2',5,5'-tetrabromo-3,3'-bi-1 H-indole, 2,2',6,6'-tetrabromo-3,3'-bi-1 H-indole and 2,2',5,5',6,6'-hexabromo-3,3'-bi-1 H-indole. In addition, palladium catalyzed, carbon monoxide mediated, double reductive N-heterocyclization of dialkenyldinitrobenzenes to the highly functionalized and highly elusive novel non-symmetrical pyrroloindoles has been developed for the first time. The methodology presents the first common synthetic routes to all isomeric pyrroloindoles which are of interest in a number of applications in addition to their presence as a core moiety in bioactive natural products. The highly functionalized isomeric cyclization precursors were prepared through the use of Kosugi-Migita-Stille coupling. The generally mild reaction conditions offer significant improvements over the previously reported synthetic routes. A facile base-mediated cyclization of enamines derived from the condensation of 2-nitroanilines with alpha-branched aldehydes, in the presence of a carbon-based electrophile, to give N-alkoxy-substituted benzimidazoles with or without an oxygenate side chain in the 2-position has also been developed. Finally, the chemoselectivity of Kosugi-Migita-Stille couplings of all isomeric permuatations of bromphenyl- and bromonitrophenyl trifluoromethanesulfonates was examined in order to compare and contrast the reactivity of C-Br and C-OTf bonds under three different reaction conditions. To the best of our knowledge, the study presented here represents the first of its kind.

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