1. Reinvestigation of a catalytic, enantioselective alkene dibromination and chlorohydroxylation, 2. Double cross-coupling reactions of siloxaborolates, 3. The enantioselective synthesis of 3-substituted morpholines using computer-guided catalyst design

Carson, Nessa

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https://hdl.handle.net/2142/95419 Copy

Description

Title

1. Reinvestigation of a catalytic, enantioselective alkene dibromination and chlorohydroxylation, 2. Double cross-coupling reactions of siloxaborolates, 3. The enantioselective synthesis of 3-substituted morpholines using computer-guided catalyst design

Author(s)

Carson, Nessa

Issue Date

2016-12-08

Director of Research (if dissertation) or Advisor (if thesis)

Denmark, Scott E.

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• Chemistry
• Siloxaborolates
• Silylboranes
• Silicon
• Boron
• Cross-coupling
• Hiyama-Denmark
• Suzuki
• Silanolates
• Enantioselective
• Dibromination
• SnAP
• Stannyl amines
• Morpholines
• Bisoxazolines
• Computational
• Modeling
• Cyclization
• Chlorohydroxylation
• Chlorohydrins
• Olefins
• Palladium
• Halofunctionalization
• Dibromides
• Predictive
• Catalytic
• Copper

Abstract

In Chapter 1, attempts to reproduce eight, putative, enantioselective dibromination and chlorohydroxylation reactions from oft-cited literature studies are described. The reactions were performed with full fidelity to the original report wherever possible. Analysis of the enantiomeric composition was performed by CSP-HPLC or CSP-SFC, as opposed to the original report, which used chiral shift reagent NMR spectroscopy. After careful study, the reported levels of enantioselectivity were found to be incorrect. Possible explanations for the false positive results are discussed. Chapter 2 moves to a completely different area of chemistry, in the Nobel Prizewinning field of cross-coupling. A bench-stable, crystalline siloxaborolate is described, capable of double cross-coupling reactions to form ortho-teraryls. The initial Suzuki reaction proceeded with high yields but the second, Hiyama-Denmark reaction proved troublesome for coupling with electron-rich aryl bromides, providing only low yields of the desired teraryls. A four-factor DoE study was undertaken to attempt to identify conditions to allow a more general scope for teraryl synthesis, however, these could not be identified in the study. Chapter 3 involves, again, a project very distinct from the other two. This took the form of synthesis and validation of a large, multipurpose set of diverse bisoxazolines of computationally-aided design. This ligand set was tasked with the enantioselective synthesis of C-substituted morpholines, for which a general and highly-selective cyclization has not yet been discovered. A number of ligands were tested for the cyclization of SnAP imines to this purpose, this being a highly general method for morpholine synthesis that previously lacked excellent enantioselectivity, and a broad spread of data was achieved for the purposes of computational modeling.

Graduation Semester

2016-12

Type of Resource

text

Permalink

http://hdl.handle.net/2142/95419

Copyright and License Information

© 2016 Nessa Carson

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