Date of Award

May 2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

M Mahmun Hossain

Committee Members

James M Cook, Arsenio A Pacheco, Xiahoua Peng, Mark L Dietz

Keywords

3,3-disubstituted Oxindole, All carbon quaternary center, Asymmetric Synthesis, C2-alkylation, Coixspirolactam A, Pd-AAA

Abstract

CHAPTER 1: PART A: A UNIQUE APPROACH OF PREPARING 3,3-DISUBSTITUTED OXINDOLES FROM ACYCLIC TETRASUBSTITUTED ALDEHYDES: TOTAL SYNTHESIS OF (-)-COERULESCINE AND (-)-COIXSPIROLACTAM A(-)-Coerulescine and (-)-coixspirolactam A, two naturally occurring compounds characterized with an all-carbon quaternary center containing a spirooxindole, have been synthesized asymmetrically. The key feature of their total synthesis involves a novel rational construction of the chiral 3,3-disubstituted oxindole core from the acyclic chiral tetrasubstituted aldehyde. The later scaffold was prepared in high enantioselectivity (up to 86%) from the ethyl 3-hydroxy-2-(2-nitrophenyl)acrylate 1 by exploring both intermolecular and intramolecular Pd-mediated asymmetric allylic allylations (Pd-AAA). A through optimization of these approaches is described in this thesis.

CHAPTER 1: PART B: SYNTHETIC SCOPE OF BRØNSTED ACID CATALYZED REACTIONS OF CARBONYL COMPOUNDS AND ETHYL DIAZOACETATE

The comprehensive study of the reactions of carbonyl compounds and ethyl diazoacetate in the presence of a Brønsted acid catalyst is described. In this, a broad range of 3-oxo esters were synthesized from a variety of ketones, specifically benzophenones and aliphatic ketones. For the diaryl ketones, we have characterized two inseparable products of migration by two-dimensional nuclear magnetic resonance spectroscopy (2D-NMR) and calculated the ratio of their relative migratory tendencies. However, the symmetric and nonsymmetrical aliphatic ketones provided the higher migration for relatively longer alkyl chains length. In case of the aliphatic aldehydes, we got exclusively the expected β-keto ester by a 1,2- hydride shift.

CHAPTER 2: INVESTIGATION OF THE C2-ALKYLATION OF 1-(1H-INDOL-3-YL)-N,N-DIMETHYLMETHANAMINE

Indole derivatives can be conveniently alkylated at the C2 position by choosing appropriate N-protecting group and appropriate base. However, 1-(1H-indol-3-yl)-N,N-dimethylmethanamine (commercially named as gramine) is also limited to that restricted choice of a protecting group for such alkylation. Herein we explore a the lithiation of gramine with different protecting groups (such as Ms, Ts, Me, TIPS etc.) on the N-heteroatom and investigate the alkylation at the C-2 position by trapping the C-2 lithio species with a variety of electrophiles such as methyl iodide, benzyl bromide, prenyl bromide, allyl bromide, etc.

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