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Asymmetric Total Synthesis of (–)-Myrifabral A and B, Havellockate, and New Strategies for Acyclic Stereocontrol

Citation

Fulton, Tyler James (2022) Asymmetric Total Synthesis of (–)-Myrifabral A and B, Havellockate, and New Strategies for Acyclic Stereocontrol. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/qb9s-xj38. https://resolver.caltech.edu/CaltechTHESIS:06062022-012944875

Abstract

Research in the Stoltz group aims, generally, to develop novel technologies for the preparation of stereochemically rich molecules and, further, to apply these technologies in the context of complex natural product total synthesis. Chapter 1 of this thesis describes the strategic utilization of a Pd-catalyzed asymmetric allylic allylation and N-acyl iminium ion cyclization to accomplish short, enantioselective total syntheses of (–)-myrifabral A and (–)-myrifabral B. Chapter 2 describes the development of a Pd-catalyzed asymmetric allylic alkylation to generate acyclic α-quaternary carboxylic acid derivatives from geometrically defined fully substituted N-acyl indole-derived allyl enol carbonates. While ester-derived enol carbonates could be prepared with a high degree of enolate geometry control, they were ineffective in the asymmetric allylic alkylation reaction. Thus, N-acyl indole substrates served as excellent carboxylic ester equivalents. Chapter 3 discusses an unusual Pd-catalyzed decarboxylative α,β-dehydrogenation reaction of N-acyl indole-derived enol carbonates enabled by a novel, highly electron-deficient phosphinooxazoline ligand. Research presented in Chapter 4 delineates a globally diastereoconvergent approach to the Ireland–Claisen rearrangement for the synthesis of α-tetrasubstituted amino acids bearing vicinal tertiary stereogenic centers. Computational investigation of the diastereoconvergence in Ireland–Claisen rearrangement revealed key intramolecular interactions which enable the reaction to proceed in exceptional diastereoselectivity without the need for a selective enolization protocol. Additionally, a diastereodivergent approach for the Ireland–Claisen rearrangement in acyclic systems to generate vicinal quaternary/tertiary and quaternary/quaternary stereogenic centers in good to high diastereoselectivity is discussed. Enolate geometry control and substrate design are critical for achieving high diastereoselectivity in these transformations.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:organic chemistry, crystallography
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Restricted to Caltech community only
Research Advisor(s):
  • Stoltz, Brian M.
Thesis Committee:
  • Reisman, Sarah E. (chair)
  • Gray, Harry B.
  • Robb, Maxwell J.
  • Stoltz, Brian M.
Defense Date:13 April 2022
Funders:
Funding AgencyGrant Number
NIH-NIGMSR01GM080269
NSFCHE-1764328
Record Number:CaltechTHESIS:06062022-012944875
Persistent URL:https://resolver.caltech.edu/CaltechTHESIS:06062022-012944875
DOI:10.7907/qb9s-xj38
Related URLs:
URLURL TypeDescription
https://doi.org/10.1039/D0SC01141JDOIArticle adapted for Chapter 1.
https://doi.org/10.1039/C9SC01726GDOIArticle adapted for Chapter 2.
https://doi.org/10.1016/j.tet.2019.05.065DOIArticle adapted for Chapter 3.
https://doi.org/10.1021/jacs.0c11480DOIArticle adapted for Chapter 4.
https://doi.org/10.1021/acscentsci.8b00760DOIArticle adapted for Appendix 11.
https://doi.org/10.1021/acscentsci.9b00403DOIArticle adapted for Appendix 12.
ORCID:
AuthorORCID
Fulton, Tyler James0000-0002-9343-2456
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:14946
Collection:CaltechTHESIS
Deposited By: Tyler Fulton
Deposited On:07 Jun 2022 15:27
Last Modified:08 Nov 2023 00:39

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