controlled hydrosilylations of carbonyl compounds and computational investigations of a hydride

102 Pages·2015·4.31 MB·English

CONTROLLED HYDROSILYLATIONS OF CARBONYL COMPOUNDS
AND COMPUTATIONAL INVESTIGATIONS OF A
HYDRIDE SHUTTLE MECHANISM FOR
ALKENE HYDROSILYLATION

by

GABRIELA TROG

Presented to the Faculty of the Graduate School of
The University of Texas at Arlington in Partial Fulfillment
of the Requirements
for the Degree of

MASTER OF SCIENCE IN CHEMISTRY

THE UNIVERSITY OF TEXAS AT ARLINGTON
December 2015
Copyright © by Gabriela Trog 2015
All Rights Reserved

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Acknowledgements
First, I would like to thank Dr. Junha Jeon for being a supportive and excellent
mentor. I greatly appreciate the knowledge I have gained under his tutelage.
I’d also like to extend heartfelt thanks to my committee members, Drs. Lovely,
Foss, and Dias, for assisting me with my proposal draft and presentation skills. Their
insight and advice have been extremely helpful and valued during my tenure at UTA.
My fellow group members and organic graduate students have been a great
source of support and advice, both in and out of the chemical sphere. Thank you all for
your assistance and companionship.
Finally, I thank my wonderful husband and son. You two mean the world to me.

November 9, 2015
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Abstract
CONTROLLED HYDROSILYLATIONS OF CARBONYL COMPOUNDS
AND COMPUTATIONAL INVESTIGATIONS OF A
HYDRIDE SHUTTLE MECHANISM FOR
ALKENE HYDROSILYLATION

Gabriela Trog, MS

The University of Texas at Arlington, 2015

Supervising Professor: Junha Jeon
Chapter 1 describes tandem dual hydrosilylations of α,β-unsaturated enals.
Hydrosilylations of both carbonyl compounds and alkenes have been utilized to create
chiral alcohols. Tandem dual hydrosilylations (TDH) of α,β-unsaturated carbonyl
compounds create five-membered oxasilacycles that can be further converted to 1,3-
diols, which are a common structural motif in the polyketide natural product family. We
present preliminary data and a substrate scope for the formation of these oxasilacycles
en route to the 1,3-diol compounds.
Chapter 2 describes hydrosilylations of esters that result in silyl acetals. The silyl
acetals are chemical synthons of the corresponding aldehyde. This reaction can be
coupled with a Horner-Wadsworth-Emmons reaction to create α,β-unsaturated esters in
good yields. Herein we present results for a limited substrate scope of the reductive
Horner-Wadsworth-Emmons reaction developed in our group.
Chapter 3 describes computational support for a proposed hydride shuttle
mechanism. The Jeon group recently disclosed a hydride shuttle mechanism for the
regio- and diastereoselective hydrosilylation of homoallylic silyl ethers when using 3-
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bromocyclohexene as a coordinating ligand with a rhodium-based catalyst. Here we
present a partial data set supporting the hydride shuttle mechanism over direct bond
formation.
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Table of Contents
Acknowledgements ........................................................................................................... iii
Abstract ............................................................................................................................. iv
List of Illustrations ............................................................................................................. viii
List of Tables ...................................................................................................................... x
List of Abbreviations .......................................................................................................... xi
Chapter 1 Tandem Dual Hydrosilylations of α,β-Unsaturated Carbonyl
Compounds ........................................................................................................................ 1
Introduction .................................................................................................................... 1
Preliminary Data ............................................................................................................ 5
Reaction Optimization .................................................................................................. 10
Substrate Scope .......................................................................................................... 12
Conclusion ................................................................................................................... 17
Chapter 2 Silyl Acetal Usage in a Reductive Horner-Wadsworth-Emmons
Olefination ........................................................................................................................ 18
Introduction .................................................................................................................. 18
Preliminary Data .......................................................................................................... 20
Silaphile Optimization .............................................................................................. 21
Minimization of Side Reactions ................................................................................ 22
Substrate Scope Investigations ................................................................................... 23
Conclusion ................................................................................................................... 24
Chapter 3 Experimental and Computational Investigation of a Rhodium-
Catalyzed Alkene Hydrosilylation Via a Hydride Shuttle Process .................................... 26
Introduction .................................................................................................................. 26
Computational Work – Methods ................................................................................... 29
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Results and Discussion ................................................................................................ 30
Conclusion ................................................................................................................... 35
Appendix A Experimental Section .................................................................................... 37
Appendix B Computational Information ............................................................................ 51
References ....................................................................................................................... 88
Biographical Information ................................................................................................... 90

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List of Illustrations
Figure 1-1 Oxopolyene macrolides .................................................................................... 1
Figure 1-2: 1,2- vs 1,4-addition of the organosilane ........................................................... 2
Figure 1-3: Ojima mechanism ............................................................................................ 3
Figure 1-4: Zheng-Chan Mechanism .................................................................................. 4
Figure 1-5: Gade silylene mechanism ................................................................................ 4
Figure 1-6: Tandem Dual Hydrosilylation ........................................................................... 5
Figure 1-6: Formation of an oxasilacycle containing chiral silane .................................... 12
Figure 1-7: TDH and ring-opening of 4-fluorocinnamaldehyde ........................................ 14
Figure 1-8: Proposed transition state for TDH of I-4F ...................................................... 15
Figure 1-9: TDH pro-substrates synthesized by the Bugarin group ................................. 15
Figure 1-10: Aliphatic substrates ...................................................................................... 16
Figure 1-11: TDH of benzylideneacetone ......................................................................... 16
Figure 2-1: Horner-Wadsworth-Emmons reaction ............................................................ 18
Figure 2-2: Comparison of metal acetal and silyl acetal ................................................... 20
Figure 2-3: One-pot formation of α-β-unsaturated esters ................................................. 20
Figure 2-4: Outline for Reductive HWE Olefination .......................................................... 21
Figure 2-5: Undesired formation of II-13b and II-13c ....................................................... 23
Figure 3-1: Chalk-Harrod and Modified Chalk-Harrod mechanisms ................................ 27
Figure 3-2: Formation of five- and six-membered oxasilacycles ...................................... 27
Figure 3-3: Trans-oxasilacycle formation using diene ligands ......................................... 28
Figure 3-4: Proposed mechanism .................................................................................... 29
Figure 3-5: Pictoral Representation of Relative Energies (kcal/mol) in Hydride Shuttle
Process ............................................................................................................................ 30
Figure 3-6: Non-hydride shuttle process in kcal/mol ........................................................ 31
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Figure 3-7: Calculated structure of transition state 5-8 .................................................... 32
Figure 3-8: “Ligand juggling” view of 5-8 .......................................................................... 33
Figure 3-9: Apparent H-sharing in 5-8 .............................................................................. 33
Figure 3-10: THF-solvated results for III-5 – III-6 ............................................................. 34
Figure 3-11: Incomplete diagram of THF-solvated hydride shuttle mechanism ............... 35
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List of Tables
Table 1-1: Catalyst Screening ............................................................................................ 6
Table 1-2: Ligand Screening .............................................................................................. 7
Table 1-3: Hydrogen acceptor studies ............................................................................... 9
Table 1-4: Norbornene as a hydrogen acceptor ................................................................. 9
Table 1-5: Norbornene study at 60 °C .............................................................................. 11
Table 1-6: Silane study ..................................................................................................... 11
Table 1-7: Initial reinvestigations of cinnamaldehydes ..................................................... 13
Table 2-1: Silaphile Optimization ...................................................................................... 22
Table 2-2: Substrate Scope Results ................................................................................. 24

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