Degree Type

Dissertation

Date of Award

2016

Degree Name

Doctor of Philosophy

Department

Chemistry

Major

Organic Chemistry

First Advisor

Levi M. Stanley

Abstract

This thesis presents the development of new catalysts for the palladium-catalyzed N-tert-prenylation of indoles, the rhodium-catalyzed endo- and enantioselective hydroacylation of ortho-allylbenzaldehydes, studies toward the rhodium-catalyzed intramolecular hydroacylation of 1,2-disubstituted alkenes, and the first examples of the rhodium-catalyzed, enantioselective hydroacylation of 1,1,2-trisubstituted alkenes.

Chapter II discusses the development of three distinct protocols for the synthesis of N-tert-prenylindoles using indole, (η6-indole)Cr(CO)3, and indoline nucleophiles. These reactions occur in the presence of the same palladium catalyst prepared in situ from readily available precursors and require loadings of the palladium catalyst that are up to ten times less than required for previously reported direct N-tert-prenylations of indoles. These methods for palladium-catalyzed N-tert-prenylation generate N-tert-prenylindoles with a range of electronic character in high yields (up to 94%) with high tert-prenyl-to-n-prenyl selectivity (up to 12:1).

Chapter III describes the development of a rhodium catalyst for endo- and enantioselective hydroacylation of ortho-allylbenzaldehydes. A catalyst generated from [Rh(COD)Cl]2, (R)-DTBM-Segphos and NaBARF promotes the enantioselective hydroacylation reactions and minimizes the formation of byproducts from competitive alkene isomerization and ene/dehydration pathways. These rhodium-catalyzed processes generate the 3,4-dihydronaphthalen-1(2H)-one products in moderate-to-high yields (49-91%) with excellent enantioselectivities (96-99% ee).

Chapter IV describes studies toward the intramolecular hydroacylation of 1,2-disubstituted alkenes as well as the first examples of catalytic, enantioselective hydroacylation of 1,1,2-trisubstituted alkenes. The intramolecular hydroacylation of 1,2-disubstituted alkenes is facilitated by a cationic rhodium complex and generates the indanone products in high yields (up to 94%). However, the α-center is prone to epimerization and results in racemic mixtures of the bicyclic products.

In contrast, the rhodium-catalyzed intramolecular hydroacylation of 1,1,2-trisubstituted alkenes generates highly enantioenriched, polycyclic architectures. The DFT and mechanistic studies presented are consistent with a reaction pathway that includes intramolecular alkene hydroacylation and α-epimerization. This reaction sequence enables the hydroacylation of 2-(cyclohex-1-en-1-yl)benzaldehydes to form hexahydro-9H-fluoren-9-ones in moderate to high yields (68-91%) with high enantioselectivities (up to 99% ee) and diastereoselectivities (typically >20:1).

DOI

https://doi.org/10.31274/etd-180810-5357

Copyright Owner

Kirsten Faye Johnson

Language

en

File Format

application/pdf

File Size

173 pages

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