Jesikiewicz, Luke
(2024)
Computational Investigations of the Diverse Factors Controlling the Mechanisms of Transition–Metal Catalyzed Carbon–Carbon Bond Forming Reactions.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
Transition metal-catalyzed reactions continue to be among the most popular synthetic methodologies for forming carbon-carbon bonds regio- and stereoselectively. Despite decades of advancements in the field, optimization of these reactions continues to be a challenge. In this work, density functional theory (DFT) calculations were performed on several transition metal-catalyzed carbon-carbon bond forming reactions including the Rh(I)-catalyzed asymmetric Pauson–Khand reaction (PKR) of 1,6-enynes, the Rh(I)-catalyzed allenic Pauson–Khand reaction (APKR), and Pd-catalyzed cross-coupling of chloroarenes. Analyses of key transition states on the reaction pathway were conducted to elucidate important insights into the dominant catalyst-substate interactions that govern transition state stability. The DFT study of the asymmetric Rh(I)-catalyzed PKR of 1,6-enynes revealed a dominant four-coordinate pathway, sterically determined mode of enantioselectivity, and factors impacting the effectiveness of the bidentate phosphine ligand class. Initial computational findings were then utilized to guide the expansion of the reaction scope and parameter selection for univariate regression. A set of molecular descriptors accurately predictive of the experimentally determined enantiomeric ratio were identified and validated by a follow-up DFT study. Careful examination of the ligand-substrate interactions during the enantioselectivity determining step of the APKR demonstrated that as the molecular complexity of the substrate increased, the level of stabilizing through-space interactions between the substrate and ligand increased in the major enantiomeric transition states. Structural information was gathered from the transition states of competing concerted and stepwise mechanisms of oxidative addition in the Pd-catalyzed cross-coupling of chloroarenes. The carbon-chlorine bond length in the chloroarene starting materials was identified as an important molecular descriptor that was then incorporated into a multivariate predictive model to determine the preference for a concerted or stepwise oxidative addition mechanism of a given substate.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Jesikiewicz, Luke | ltj6@pitt.edu | ltj6 | |
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| ETD Committee: |
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| Date: |
20 December 2024 |
| Date Type: |
Publication |
| Defense Date: |
5 September 2024 |
| Approval Date: |
20 December 2024 |
| Submission Date: |
25 October 2024 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
125 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Computational Chemistry, Organic Chemistry, Transition Metal Catalysis, Density Functional Theory, Reaction Mechanism, Pd-catalyzed Cross-coupling, Pauson-Khand Reaction |
| Date Deposited: |
20 Dec 2024 14:17 |
| Last Modified: |
20 Dec 2024 14:17 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/47041 |
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Computational Investigations of the Diverse Factors Controlling the Mechanisms of Transition–Metal Catalyzed Carbon–Carbon Bond Forming Reactions. (deposited 20 Dec 2024 14:17)
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