Qi, Yifan
(2024)
Catalyst-Controlled Asymmetric Rh(I)-Catalyzed Pauson-Khand Reaction.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
The asymmetric Pauson-Khand reaction (PKR) represents a powerful approach for synthesizing 5,5 and 5,6-ring systems, which are prevalent in natural products and bioactive compounds. Despite considerable efforts towards understanding the asymmetric PKR, the scope of this transformation is still quite limited. Herein, we present a systematic study aimed at identifying key reaction parameters governing the reactivity and selectivity of the asymmetric Rh(I)-catalyzed PKR using 1,6-enyne precursors featuring a 2,2-disubstituted alkene and chiral bisphosphine ligands. This transformation leads to the formation of ring-fused cyclopentenones containing an all-carbon quaternary stereogenic center, which are challenging synthetic motifs. We compared experimental enantioselectivity, ln(er) data, for two enyne substrates with 181 computed descriptors of a chiral bisphosphine Pd(II)Cl2 complex, and established high correlations between an energy of Pd lone pair orbital or aryl-P-aryl angle depending on the enyne tether. Our findings also revealed that solvent properties, such as dipole moment (D) and Abraham’s hydrogen bond basicity (β), correlate well with PKR ln(er). Notably, a precatalyst featuring low ion pairing (e.g. OTf-) is advantageous for enynes featuring an N-tosyl and ether tether, whereas a precatalyst with high ion pairing (e.g. BF4-) gives better overall results for enynes with a carbon tether. Additionally, the calculated dipole moment of the enyne precursor influences solvent selection, and the calculated IR C≡C wavenumber (cm-1) indicates reactivity.
In a separate study, chiral phosphoramidite ligands with bulky amine groups, such as dibenzazepine, induce chirality inversion, relative to a dimethylamine group. A morpholine group speeds up the reaction significantly and gives PKR product in higher %ee. We demonstrated the application of these findings by desymmetrizing a prochiral dienyne to give the PKR product in high yield, high %ee and high dr.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
20 December 2024 |
| Date Type: |
Publication |
| Defense Date: |
15 November 2024 |
| Approval Date: |
20 December 2024 |
| Submission Date: |
10 October 2024 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
343 |
| 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: |
catalyst-control, asymmetric Pauson-Khand reaction, chiral quaternary carbon centers, solvent effect, counterion effect, phosphorous ligand effect, descriptor selection |
| Date Deposited: |
20 Dec 2024 14:14 |
| Last Modified: |
20 Dec 2024 14:14 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/47006 |
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