Xia, Yue
(2024)
Cross-Dehydrogenative Coupling Facilitated by Iron Mediated C–H Functionalization Adjacent to π Bonds.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
The functionalization of C–H bonds adjacent to π bonds offers great opportunity for the diversification of synthetically useful molecules. The integration of this C–H functionalization strategy with cross-dehydrogenative coupling (CDC), which eliminates the necessity for substrate prefunctionalization, is a useful alternative for the synthesis of functionalized molecules from readily available starting materials. Herein, this dissertation describes two distinct strategies for iron-mediated cross-dehydrogenative coupling using alkyne and allene precursors.
The regioselective coupling of unactivated allenes and tetrahydroisoquinolines (THIQs) was achieved via the in-situ formation of a nucleophilic organometallic species through iron-assisted allenic C–H deprotonation, followed by its addition to dihydroisoquinolinium electrophile, which was obtained from tetrahydroisoquinoline via hydride abstraction. The transformation represented a compelling approach for the quick assembly and diversification of C1 substituted tetrahydroisoquinolines, which are prevalent scaffolds in natural products and bioactive compounds.
A distinct strategy for the chemo- and regioselective coupling of alkynes and alcohols was next developed. A nucleophilic organoiron species was prepared from alkyne via iron-assisted propargylic C–H deprotonation. In contrast to prior strategies based on electrophilic functionalization, this cross-dehydrogenative coupling reaction leveraged oxidation induced reversal of reactivity of this organometallic complex, facilitating subsequent coupling with alcohol nucleophiles. This unique organometallic umpolung approach enabled the previously unattained etherification of propargylic C–H bonds and proceeded with excellent functional group tolerance and chemoselectivity. Our findings revealed that the oxidant’s oxidation potential and electron transfer efficiency between oxidant and organoiron species correlated well with reactivity. Mechanistic studies suggested that a transient intermediate with radical character was generated via single-electron oxidation of the organoiron species.
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| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
19 December 2024 |
| Date Type: |
Publication |
| Defense Date: |
3 December 2024 |
| Approval Date: |
19 December 2024 |
| Submission Date: |
6 December 2024 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
286 |
| 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: |
C–H Functionalization, Cross-Dehydrogenative Coupling, Organometallic Chemistry |
| Date Deposited: |
19 Dec 2024 21:10 |
| Last Modified: |
19 Dec 2024 21:10 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/47191 |
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