CaltechTHESIS
  A Caltech Library Service

Progress Toward an Enantioselective Total Synthesis of Ineleganolide

Citation

Roizen, Jennifer Lyn (2010) Progress Toward an Enantioselective Total Synthesis of Ineleganolide. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z93F4MMN. http://resolver.caltech.edu/CaltechTHESIS:11172009-113840501

Abstract

Investigations toward an enantioselective total synthesis of ineleganolide (1) are disclosed. These studies have driven the development of a novel asymmetric ketone alkylation to form C(α)-tetrasubstituted carbonyl compounds. Products of these alkylations have been converted to α-hydroxy ketones, acids, and esters, completing an asymmetric formal synthesis of (–)-quinic acid.

Additionally, one of these products, a chloroalkene, has been advanced in the synthesis of the [6–7–5–5]-fused core of ineleganolide. The chloroalkene can be converted through a mild oxidative bromination, Wittig olefination, and Luche reduction sequence to rapidly access the enantioenriched cyclopentenol fragment of ineleganolide. Two of these alcohols can be coupled with a cyclohexenone-derived carboxylic acid to append the six-membered ring fragment. These flexible vinylogous β-ketoesters can be advanced to a rigid [5–5–3]-fused cyclopropane.

At the outset of this work, we envisioned the advancement of a [5–5]-fused cyclopropane through a tandem Wolff/Cope rearrangement to access the [6–7–5–5]-fused core of ineleganolide. Synthetic studies toward this rearrangement are described. Additionally, we explore a translactonization/Cope rearrangement and a cyclopropanation/Cope/epoxidation cascade sequence to access the [6–7–5–5]-fused scaffold. In the course of these efforts, a rich body of chemistry has been developed exploring translactonizations in cis-substituted cyclopentane diols, including the translactonization/Cope cascade.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:ineleganolide, asymmetric, total synthesis, enantioselective decarboxylative alkylation, fully-substituted ether, tertiary alcohol, Cope, Wolff-Cope, translactonization, cyclopropanation
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Awards:Tobacco-Related Disease Research Program (TRDRP) Dissertation Award, 2005
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Stoltz, Brian M.
Thesis Committee:
  • Bercaw, John E. (chair)
  • Grubbs, Robert H.
  • Dougherty, Dennis A.
  • Stoltz, Brian M.
Defense Date:15 October 2009
Funders:
Funding AgencyGrant Number
California Tobacco-Related Disease Research Program14DT-0004
NIH-NIGMSR01 GM 080269-01
Record Number:CaltechTHESIS:11172009-113840501
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:11172009-113840501
DOI:10.7907/Z93F4MMN
Related URLs:
URLURL TypeDescription
http://stoltz.caltech.eduOtherAdvisor website
http://dx.doi.org/10.1002/anie.200801424DOIArticle adapted for ch. 4
ORCID:
AuthorORCID
Roizen, Jennifer Lyn0000-0002-6053-5512
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5378
Collection:CaltechTHESIS
Deposited By: Jennifer Roizen
Deposited On:02 Mar 2017 23:53
Last Modified:19 Mar 2018 21:02

Thesis Files

[img]
Preview
PDF (Table of Contents) - Final Version
See Usage Policy.

258Kb
[img]
Preview
PDF (Ch. 1: Ineleganolide and Related Natural Products) - Final Version
See Usage Policy.

797Kb
[img]
Preview
PDF (Ch. 2: Polycyclic Natural Products as Inspiration for the Development of the Tandem Wolff/Cope Rearrangement) - Final Version
See Usage Policy.

634Kb
[img]
Preview
PDF (Appendix 1: The Wolff Rearrangement) - Final Version
See Usage Policy.

980Kb
[img]
Preview
PDF (Appendix 2: The Cope Rearrangement) - Final Version
See Usage Policy.

472Kb
[img]
Preview
PDF (Ch. 3 + Appendix 3: Computational and Synthetic Validation of a Wolff/Cope Approach to Ineleganolide) - Final Version
See Usage Policy.

2588Kb
[img]
Preview
PDF (Ch. 4 + Appendix 4: Catalytic Enantioselective Aklylation of Dioxanone Enol Ethers) - Final Version
See Usage Policy.

25Mb
[img]
Preview
PDF (Ch. 5: A Convergent Approach to Ineleganolide) - Final Version
See Usage Policy.

2751Kb
[img]
Preview
PDF (Appendix 5: Similar Translactonization in Bielshowskysin, a Related System) - Final Version
See Usage Policy.

224Kb
[img]
Preview
PDF (Appendix 6: Spectra of Compounds Relevant to Chapter Five) - Final Version
See Usage Policy.

16Mb
[img]
Preview
PDF (Appendix 7: S-Ray Crystallography Reports Relevant to Chapter Five) - Final Version
See Usage Policy.

273Kb
[img]
Preview
PDF (Appendix 8: Notebook Cross-Reference) - Final Version
See Usage Policy.

1078Kb
[img]
Preview
PDF (Index) - Final Version
See Usage Policy.

61Kb
[img]
Preview
PDF (Comprehensive Bibliography) - Final Version
See Usage Policy.

320Kb
[img]
Preview
PDF (About the Author) - Final Version
See Usage Policy.

30Kb

Repository Staff Only: item control page