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I. Synthetic Studies Toward the Total Synthesis of Polycyclic Natural Products – Communesin F, Perophoramidine and Ineleganolide. II. Nickel Catalyzed Intramolecular C–O Bond Formation

Citation

Han, Seojung (2016) I. Synthetic Studies Toward the Total Synthesis of Polycyclic Natural Products – Communesin F, Perophoramidine and Ineleganolide. II. Nickel Catalyzed Intramolecular C–O Bond Formation. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9NV9G6M. http://resolver.caltech.edu/CaltechTHESIS:05172016-222905476

Abstract

Expedient synthetic approaches to the highly functionalized polycyclic alkaloids communesin F and perophoramidine are described using a unified approach featuring a key decarboxylative allylic alkylation to access a crucial and highly congested 3,3-disubstituted oxindole. Described are two distinct, stereoselective alkylations that produce structures in divergent diastereomeric series possessing the critical vicinal all-carbon quaternary centers needed for each synthesis. Synthetic studies toward these challenging core structures have revealed a number of unanticipated modes of reactivity inherent to these complex alkaloid scaffolds. Finally, a previously unknown mild and efficient deprotection protocol for the o-nitrobenzyl group is disclosed – this serendipitous discovery permitted a concise endgame for the formal syntheses of both communesin F and perophoramidine.

In addition, the atroposelective synthesis of PINAP ligands has been accomplished via a palladium-catalyzed C–P coupling process through dynamic kinetic resolution. These catalytic conditions allow access to a wide variety of alkoxy- and benzyloxy-substituted PINAP ligands in high enantiomeric excess.

An efficient and exceptionally mild intramolecular nickel-catalyzed carbon–oxygen bond-forming reaction between vinyl halides and primary, secondary, and tertiary alcohols has been achieved. This operationally simple method allows direct access to cyclic vinyl ethers in high yields in a single step.

Finally, synthetic studies toward polycyclic ineleganolide are described. The entire fragmented carbon framework has been constructed from this work. Highly (Z)-selective olefination was achieved by the method by the Ando group.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Synthesis; Natural Products; Communesin F; Perophoramidine; PINAP; Dynamic kinetic resolution; Cross-coupling; Ineleganolide
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)
  • Stoltz, Brian M.
  • Agapie, Theodor
  • Grubbs, Robert H.
Defense Date:13 May 2016
Funders:
Funding AgencyGrant Number
Fulbright15111120
ILJU Foundation of Education & CultureUNSPECIFIED
Record Number:CaltechTHESIS:05172016-222905476
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:05172016-222905476
DOI:10.7907/Z9NV9G6M
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ol5013263DOIArticle adapted for ch.1
http://dx.doi.org/10.1021/jo502534gDOIArticle adapted for ch.1
http://dx.doi.org/10.1021/ar5004658DOIArticle adapted for ch.1
http://dx.doi.org/10.1016/j.tetlet.2014.10.006DOIArticle adapted for ch.2
http://dx.doi.org/10.1002/anie.201601991DOIArticle adapted for ch.4
http://dx.doi.org/10.1016/j.tet.2014.10.065DOIArticle adapted for appendix 4
http://dx.doi.org/10.1016/j.tetlet.2016.04.022DOIArticle adapted for appendix 11
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:9727
Collection:CaltechTHESIS
Deposited By: Seojung Han
Deposited On:19 May 2016 21:22
Last Modified:19 May 2016 21:22

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