Synthesis of benzo-fused nitrogen heterocycles and substituted benzenes

• Author / Creator

  Ziffle, Vincent

• The first chapter of this thesis represents the continued development of a general method for the formation of benzo-fused N-heterocycles by formal radical cyclization onto benzene rings. Important stages in this process involve 1) the copper-mediated coupling of various amino alcohols to protected p-iodophenols, 2) carbamate-protection of the resulting aryl secondary amine to allow the following oxidation step, 3) the oxidative formation of quinone ketals as radical acceptors, 4) the radical cyclization of pendant iodo-radical triggers onto the cross-conjugated ketone, and 5) the subsequent aromatization of the resulting products into benzo-fused N-heterocycles. Various protected 2,3-dihydroindoles—some of which with 2-substitutions—have been synthesized using this methodology. For some examples, it was necessary to repeat the experiments of a previous group member to obtain publication-quality data.
  
  The second chapter describes a new methodology for the formation of regioselectively-substituted benzene rings. Various arene species have been synthesized in p-disubstituted, 1,2,4-trisubstituted and 1,2,3,4-tetrasubstituted arrays. Key steps in the methodology include 1) the synthesis of 1,4-diketones by alkylation of various aldehydes and their subsequent reduction and oxidation, 2) addition of organometallic alkenes to 1,4-diketones to form ring closing metathesis (RCM) precursors, and 3) RCM and subsequent aromatization of these cyclized products by double-dehydration to form the desired substituted benzenes. The macrocycle [12]-paracyclophane has also been synthesized using a modified version of the above methodology.

• Subjects / Keywords

  • Aromatization
  • Dihydroindole
  • Benzene
  • Radical
  • Cyclization

• Graduation date

  Spring 2010

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R38Q43

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.