Dissertation
Access to highly functionalized monocyclic cyclopentenones via the exploitation of labile silicon tethered 1,7-enynes
Doctor of Philosophy (Ph.D.), Drexel University
Aug 2021
DOI:
https://doi.org/10.17918/00000888
Abstract
A diastereoselective, catalytic Co2(CO)8-mediated Pauson-Khand reaction (PKR) of siloxy- and silaza-tethered 1,7-enynes for the synthesis of cyclopentaoxasilinones and cyclopentazasilinones has been developed. Oxidation of the resulting labile tether delivers stereoenriched [beta]-alkylated cyclopentenones, which are inaccessible by intermolecular PKRs. Since its initial discovery in 1973, the intra- and intermolecular PKRs have been exemplified as a convergent, atom-economical, and fundamental reaction for the [2+2+1] synthesis of cyclopentenones. However, the intermolecular PKR has generally been limited to strained or symmetrical alkenes due to the difficulty controlling the alkene regio- and stereoselectivity. Therefore, a general stereoselective PKR strategy to access highly functionalized monocyclic cyclopentenones remains an unsolved challenge. Herein, we describe the use of 1,7- enynes bearing a removable silicon tether, that upon oxidation of the Si-C bond, gives rise to highly functionalized and stereoenriched monocyclic cyclopentenones. The utilization of secondary propargylic alcohols bearing an allylic olefin has led to unprecedented diastereoselectivity in the synthesis of cyclopentaoxasilinones bearing functionalizable handles that allow for the rapid introduction of stereochemical complexity and structural diversity around the cyclopentane core in upward of six (6) contiguous stereocenters. Experimental and computational investigations have shown a favorable secondary coordination of the pendant olefin to the acyclic cobalt atom of the dimeric catalyst Co2(CO)8. The discovery of the recoverable/reusable thioether, namely 4-fluorobenzyl(methyl)sulfide (4-FBnSMe), led to both a sharp increase in the yield and the dropping the catalytic loading of Co2(CO)8 from 100 mol% to as low as 2.5 mol% under 1atm of CO(g). To minimize the cost and risk of exposure to carbon monoxide gas, we developed the first two-chambered catalytic Pauson-Khand Reaction that utilizes ex-situ generated carbon monoxide gas (CORMs) from commercially available and cheap commodity chemicals. Multiple different known transition metal catalysts and CORMs have been shown to promote the reaction, showing the versatility of this cheaper and safer complementary method to produce cyclopentenones via the Pauson-Khand Reaction.
Metrics
45 File views/ downloads
86 Record Views
Details
- Title
- Access to highly functionalized monocyclic cyclopentenones via the exploitation of labile silicon tethered 1,7-enynes
- Creators
- Austin Gregory Gallagher
- Contributors
- Dionicio Martinez-Solorio (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xii, [689] pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Arts and Sciences; Chemistry; Drexel University
- Other Identifier
- 991015606466704721