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Development of a novel ring contraction strategy and application to the total synthesis of presilphiperfolanol natural products

Citation

Hong, Allen Yu (2013) Development of a novel ring contraction strategy and application to the total synthesis of presilphiperfolanol natural products. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9WW7FMB. http://resolver.caltech.edu/CaltechTHESIS:12192012-071010744

Abstract

Biologically active and structurally complex natural products provide a powerful driving force for the development of novel reaction methodology. Major advances can reshape the way chemists approach the construction of challenging chemical bonds.

In this work, we begin by describing the development of a catalytic asymmetric synthesis of five and seven-membered rings containing all-carbon quaternary stereocenters. Enantioselective Pd-catalyzed decarboxylative allylic alkylation reactions of β-ketoester substrates afforded a variety of chiral seven-membered α-quaternary vinylogous esters. Initial attempts to convert these compounds to γ-quaternary cycloheptenones led to the discovery of a two-carbon ring contraction reaction, which provided isomeric γ-quaternary acylcyclopentenes. Subsequent adjustment of reaction parameters provided divergent access to the originally targeted cycloheptenones. Numerous synthetic applications of the two versatile product types are demonstrated. The methodology expands on our previous investigations of six-membered ring scaffolds and provides additional chiral building blocks for asymmetric total synthesis.

The ring contraction approach to acylcyclopentenes was further developed in the total synthesis of the presilphiperfolanols, which are important intermediates in sesquiterpene biosynthesis. Key to our synthetic route to the tricyclic core was the application of intramolecular Diels–Alder and Ni-catalyzed 1,4-hydroboration reactions. From these efforts, the enantioselective total synthesis of presilphiperfolan-1β-ol was achieved. Future research efforts seek to extend the synthetic route to presilphiperfolan-9α-ol and study the synthetic compounds in biomimetic carbocation rearrangement processes.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:synthetic methods; reaction methodology; palladium; asymmetric allylic alkylation; asymmetric catalysis; vinylogous ester; unusual reactivity; reduction; ring contraction; rearrangement; divergent synthesis; derivatization; total synthesis; natural products; sesquiterpenoids; presilphiperfolanols; biosynthesis; structure determination; Diels–Alder reaction; 1,4-hydroboration; allylic substitution; hydrogenation
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Awards:Roche Excellence in Chemistry Award, Abbott Scholars Symposium Award
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Stoltz, Brian M.
Thesis Committee:
  • Bercaw, John E. (chair)
  • Reisman, Sarah E.
  • Tirrell, David A.
  • Virgil, Scott C.
  • Stoltz, Brian M.
Defense Date:7 December 2012
Funders:
Funding AgencyGrant Number
NIH-NIGMSR01GM080269-01
Record Number:CaltechTHESIS:12192012-071010744
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:12192012-071010744
DOI:10.7907/Z9WW7FMB
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1002/ejoc.201201761DOIReview adapted from ch.1
http://dx.doi.org/10.1002/anie.201007814DOICommunication adapted from ch.2
http://dx.doi.org/10.1039/c1ob06189eDOICommunication adapted from ch.2
http://dx.doi.org/10.1016/j.tet.2011.10.031DOIFull Article adapted from ch. 2
http://dx.doi.org/10.1002/anie.201205276DOICommunication adapted from ch.2
http://dx.doi.org/10.1002/anie.201205276DOICommunication adapted from ch.3
http://dx.doi.org/10.1002/anie.201309494DOIReview adapted from ch.3
http://dx.doi.org/10.1038/nchem.297DOIReview adapted from Appendix 9
http://dx.doi.org/10.1021/jacs.6b02153DOICommunication adapted from Appendix 11
ORCID:
AuthorORCID
Hong, Allen Yu0000-0002-4691-548X
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:7342
Collection:CaltechTHESIS
Deposited By: Allen Hong
Deposited On:12 Jan 2015 18:44
Last Modified:22 Aug 2016 21:24

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