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Palladium(II)-catalyzed oxidation reactions in natural product synthesis : efforts toward bielschowskysin and phalarine

Citation

Meyer, Michael Elliott (2011) Palladium(II)-catalyzed oxidation reactions in natural product synthesis : efforts toward bielschowskysin and phalarine. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechTHESIS:08042010-151446303

Abstract

Two types of oxidative transformations, an oxidative kinetic resolution and an oxidative heterocyclization, have been developed by several laboratories using palladium(II)-catalysis to provide enantioenriched products. The main drawback of these asymmetric transformations is the limited substrate scope for each set of conditions. To address this, the Stoltz laboratory developed a unique platform utilizing palladium(II)-catalysis that provides a highly effective oxidative kinetic resolution of secondary alcohols and an asymmetric oxidative heterocyclization of phenols. Key to this platform is the use of (–)-sparteine as the chiral ligand and O2 as the stoichiometric oxidant. Both of these methodologies will be featured in this thesis as they were applied toward the total synthesis of complex natural products. Our palladium(II)-catalyzed oxidative kinetic resolution was used to access an enantioenriched intermediate in our efforts toward the synthesis of bielschowskysin, a polycyclic diterpenoid. A key disconnection in our strategy was formation of the cyclobutane core of bielschowskysin from a cyclopropane intermediate. After considerable experimentation, we were able to synthesize a cyclopropane intermediate that could be used for future research. In separate work, we hoped to use two palladium(II)-catalyzed oxidative heterocyclization reactions to provide the core of phalarine, a polycyclic alkaloid. The synthesis of a key intermediate relied on a Stille coupling reaction of a complex 4,5,7-substituted indole and a nitro-arene. Model cyclization studies on an aniline substrate gave inconclusive results, while a model of a phenolic substrate has shown that cyclization onto styrenyl olefins is possible.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Palladium, Oxidative Cyclization, bielschowskysin, phalarine
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:
  • Grubbs, Robert H. (chair)
  • Bercaw, John E.
  • Reisman, Sarah E.
Defense Date:28 June 2010
Record Number:CaltechTHESIS:08042010-151446303
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:08042010-151446303
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5986
Collection:CaltechTHESIS
Deposited By: Michael Meyer
Deposited On:23 Dec 2010 19:25
Last Modified:26 Dec 2012 04:29

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