Degree Type

Dissertation

Date of Award

2019

Degree Name

Doctor of Philosophy

Department

Chemistry

Major

Organic Chemistry

First Advisor

Levi M. Stanley

Abstract

This thesis presents the development of bismuth(III) triflate-promoted conjugate additions of electron-rich heteroarenes to ,-disubstituted enones, regioselective 1,6-additions of electron-rich heteroarenes to dienones, and 1,2-addition of nucleophilic heteroarenes to progesterone, 17-hydroxyprogesterone acetate and andrenosterone. Additionally, this dissertation describes the first examples of intermolecular alkene carboacylation triggered by amide CN bond activation.

Chapter II discusses the development of catalytic conjugate additions of heteroarenes to ,-disubstituted enones. Additions of a range of heteroarene nucleophiles, including furans, indoles, pyrroles, and thiophenes to a variety of ,-disubstituted enones occur to form heteroarylated all-carbon quaternary centers in up to 90% yield. These reaction occur under mild reaction conditions in the presence of low loadings of bismuth(III) triflate.

Chapter III describes the development and optimization of bismuth(III) triflate-promoted regioselective 1,6-additions of electron-rich heteroarenes to dienones. Regioselective 1,6-additions of a range of electron-rich heteroarenes, including furan, thiophene, pyrrole, and indole nucleophiles to 3-vinyl-2-cyclohexenone occur to produce a variety of -heteroarylated, ,-disubstituted enones in up to 93% yield. The high 1,6-selectivity for these reactions is attributed to the increased steric bulk at the -position relative to the -position, and no competing 1,4-conjugate addition is observed.

Chappter IV describes 1,2-additions of heteroarenes to hormone steroids. Additions of a range of electron-rich heteroarene nucleophiles, including indoles, a pyrrole, and a thiophene, to a variety of commercially available steroids and subsequent dehydration occur to form 3-heteroarylated steroidal dienes in up to 93% yield. This atom-economical reaction sequence occurs under mild reaction conditions in the presence of catalytic bismuth triflate.

Chapter V discusses studies toward nickel-catalyzed intermolecular carboacylation of alkenes with amides and tetraarylborates. Bicyclic alkenes are readily functionalized with a variety of N-benzoyl-N-phenylbenzamides and triarylboranes, which are generated in situ from the corresponding tetraarylborates, to synthesize ketone products in up to 91% yield. This reaction manifold is initiated by activation of the amide CN bond via oxidative addition by a Ni(0) catalyst. Preliminary mechanistic studies suggest that migratory insertion precedes transmetalation, and that reductive elimination is the turnover-limiting step. These reactions occur with excellent chemoselectivity and diastereoselectivity in the absence of a directing/chelating group and further demonstrate amides as practical acyl electrophiles for alkene functionalization reactions.

Copyright Owner

Tanner Lee Metz

Language

en

File Format

application/pdf

File Size

141 pages

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