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


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.


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:Public (worldwide access)
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
Funding AgencyGrant Number
Record Number:CaltechTHESIS:06062022-012944875
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for Chapter 1. adapted for Chapter 2. adapted for Chapter 3. adapted for Chapter 4. adapted for Appendix 11. adapted for Appendix 12.
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
Deposited By: Tyler Fulton
Deposited On:07 Jun 2022 15:27
Last Modified:08 May 2024 17:21

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