Degree Type

Dissertation

Date of Award

2003

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Richard C. Larock

Abstract

A variety of substituted beta- and gamma-carbolines containing aryl, alkyl, hydroxymethyl, ester and silyl functionality at the 3- and 4-positions have been prepared by the palladium-catalyzed iminoannulation of internal and terminal alkynes. This methodology has been successfully employed to the synthesis of two biologically active beta-carboline alkaloids, ZK93423 and abecarnil.;A variety of 3-substituted beta- and gamma-carbolines have been synthesized from N-substituted 3-iodo-1H-indole-2-carboxaldehydes and 2-bromo-1H-indole-3-carboxaldehydes, respectively. The coupling of these aldehydes with various terminal acetylenes using cat. PdCl 2(PPh3)2/CuI readily affords the corresponding alkynylindole carboxaldehydes, which have subsequently been converted to the corresponding tert-butylimines and cyclized to beta- and gamma-carbolines by either copper-catalyzed or thermal processes.;A variety of N-substituted 2-bromo-1H-indole-3-carboxaldehydes incorporating an alkyne-containing tether on the indole nitrogen have been converted to the corresponding tert-butylimines, which have been subjected to palladium-catalyzed intramolecular iminoannulation, affording various gamma-carboline derivatives with an additional ring fused across the 4- and 5-positions in good to excellent yields. This "intramolecular" concept has been extended to other palladium-catalyzed annulations to synthesize various complex heteropolycycles.;A novel 1,4-palladium migration has been observed by trapping the palladium intermediate generated from o-iodobiaryls by way of a Suzuki coupling reaction. The choice of reaction conditions is important in turning "on" and "off" the migration. There are important electronic effects controlling the distribution of the palladium intermediates, which is reflected in the isomer distribution of the Suzuki products.

DOI

https://doi.org/10.31274/rtd-180813-9908

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu

Copyright Owner

Haiming Zhang

Language

en

Proquest ID

AAI3085963

File Format

application/pdf

File Size

394 pages

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