Towards a biosynthetically inspired synthesis of bromochlorinated medium ring ethers of laurencia species by intermolecular bromonium ion induced reactions
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Author(s)
Al-Gharebawi, Yusrah
Type
Thesis
Abstract
The research presented herein describes a biosynthetically inspired approach to the bromochlorinated 7-, 8- and 9-membered medium ring ethers of the Laurencia species by intermolecular bromonium ion induced reactions. This thesis has been separated into three major chapters; including an experimental cataloguing the experimental procedures and spectroscopic data. An Appendix is also provided, which describes additional work.
Chapter 1 provides the prior total syntheses of the bromochlorinated medium ring ethers of the Laurencia species. Preceding literature on relevant intramolecular and intermolecular bromonium ion assisted epoxide ring opening reactions (intra-BIAERO and inter-BIAERO, respectively) are also discussed.
Chapter 2 introduces a biosynthetically inspired approach to the total synthesis of the desired 7-, 8- and 9-membered medium ring ethers of the Laurencia species. Model 1,2-disubstituted acyclic alkenes A.1 and 1,2-disubstituted acyclic epoxides A.2 were combined in an attempted inter-BIAERO (Scheme 1). Various exogenous nucleophiles were investigated including TMSCl, TBAC and LiCl. NBS was the chosen brominating agent. The inter-BIAERO reactions were unsuccessful and proposed to be sterically hindered by the presence of the doubly protected TBDPS/TIPS alcohols.
Scheme 1. Model 1,2-disubstituted acyclic alkenes A.1 and 1,2-disubstituted acyclic epoxides A.2 were combined in an attempted inter-BIAERO but failed to produce the desired haloethers A.3 and A.4.
However, employing model 1,2-disubstituted cyclic alkene A.5 and 1,2-disubstituted cyclic epoxide A.6 in a route that also takes advantage of an inter-BIAERO reaction in the presence of NBS as a brominating agent was more successful (Scheme 2.1). Various external nucleophiles were explored in the inter-BIAERO coupling reaction including several substituted benzoic acids A.7. The inter-BIAERO reaction produced the desired bromobenzoate ethers A.8 and A.9; model precursors to the desired 7-, 8- and 9-membered medium ring ethers of the Laurencia species and bromobenzoate A.10.
Scheme 2.1. Model 1,2-disubstituted cyclic alkene A.5 and 1,2-disubstituted cyclic epoxide A.6 were coupled in a successful inter-BIAERO reaction that provided the desired model bromobenzoate ethers A.8 and A.9.
The successful conditions for the inter-BIAERO reaction (Scheme 2.1) were modified and employed in the coupling of 1,4-cyclohexadiene A.11 and cis-diepoxide A.12 (Scheme 2.2). This provided the desired epoxy bromobenzoate ethers A.13 an A.14, precursors to the bromochlorinated 7-, 8- and 9-membered medium ring ethers of the Laurencia species, alongside bromobenzoate A.15.
Scheme 2.2. 1,4-Cyclohexadiene A.11 and cis-diepoxide A.12 were coupled in a successful inter-BIAERO reaction that provided the desired epoxy bromobenzoate ethers A.13 an A.14, alongside bromobenzoate A.15
Chapter 1 provides the prior total syntheses of the bromochlorinated medium ring ethers of the Laurencia species. Preceding literature on relevant intramolecular and intermolecular bromonium ion assisted epoxide ring opening reactions (intra-BIAERO and inter-BIAERO, respectively) are also discussed.
Chapter 2 introduces a biosynthetically inspired approach to the total synthesis of the desired 7-, 8- and 9-membered medium ring ethers of the Laurencia species. Model 1,2-disubstituted acyclic alkenes A.1 and 1,2-disubstituted acyclic epoxides A.2 were combined in an attempted inter-BIAERO (Scheme 1). Various exogenous nucleophiles were investigated including TMSCl, TBAC and LiCl. NBS was the chosen brominating agent. The inter-BIAERO reactions were unsuccessful and proposed to be sterically hindered by the presence of the doubly protected TBDPS/TIPS alcohols.
Scheme 1. Model 1,2-disubstituted acyclic alkenes A.1 and 1,2-disubstituted acyclic epoxides A.2 were combined in an attempted inter-BIAERO but failed to produce the desired haloethers A.3 and A.4.
However, employing model 1,2-disubstituted cyclic alkene A.5 and 1,2-disubstituted cyclic epoxide A.6 in a route that also takes advantage of an inter-BIAERO reaction in the presence of NBS as a brominating agent was more successful (Scheme 2.1). Various external nucleophiles were explored in the inter-BIAERO coupling reaction including several substituted benzoic acids A.7. The inter-BIAERO reaction produced the desired bromobenzoate ethers A.8 and A.9; model precursors to the desired 7-, 8- and 9-membered medium ring ethers of the Laurencia species and bromobenzoate A.10.
Scheme 2.1. Model 1,2-disubstituted cyclic alkene A.5 and 1,2-disubstituted cyclic epoxide A.6 were coupled in a successful inter-BIAERO reaction that provided the desired model bromobenzoate ethers A.8 and A.9.
The successful conditions for the inter-BIAERO reaction (Scheme 2.1) were modified and employed in the coupling of 1,4-cyclohexadiene A.11 and cis-diepoxide A.12 (Scheme 2.2). This provided the desired epoxy bromobenzoate ethers A.13 an A.14, precursors to the bromochlorinated 7-, 8- and 9-membered medium ring ethers of the Laurencia species, alongside bromobenzoate A.15.
Scheme 2.2. 1,4-Cyclohexadiene A.11 and cis-diepoxide A.12 were coupled in a successful inter-BIAERO reaction that provided the desired epoxy bromobenzoate ethers A.13 an A.14, alongside bromobenzoate A.15
Version
Open Access
Date Issued
2020-12
Date Awarded
2021-03
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Braddock, David Christopher
Sponsor
Engineering and Physical Sciences Research Council (EPSRC)
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)