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Development of new asymmetric organocatalytic methods and progress towards the total synthesis of guanacastepene A

Citation

Jen, Wendy S. (2004) Development of new asymmetric organocatalytic methods and progress towards the total synthesis of guanacastepene A. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-10282003-135857

Abstract

The development of a new iminium-activation approach towards asymmetric organic catalysis is described. This strategy has been successfully applied to a 1,3-dipolar cycloaddition reaction to produce the first enantioselective catalytic [3+2]cycloaddition between nitrones and a,b-unsaturated aldehydes. This methodology highlights the ability of this new organocatalytic strategy to access chemical transformations not attainable though traditional Lewis acid catalysis.

We have also applied this iminium-activation strategy towards the successful development of an enantioselective organocatalytic intramolecular Diels-Alder (IMDA) reaction. This variant of the IMDA reaction is capable of accessing a range of stereochemically complex [4.3.0] and [4.4.0] ring systems in good yields and with excellent selectivities. Furthermore, we have successfully developed the first asymmetric Type II intramolecular Diels-Alder cyclization. Finally, the utility of this methodology was demonstrated in the efficient total synthesis of (?)-solanapyrone D where an asymmetric organocatalytic IMDA reaction comprised the pivotal bond construction.

Progress has been made towards the total synthesis of guanacastepene A. Significant efforts were directed towards a pursuing a 3-component coupling/intramolecular Diels-Alder approach towards the natural product. IMDA precursors were synthesized in an efficient and convergent manner. It was found, however, that these substrates were unable to undergo the desired cyclization. By modifying our synthetic approach towards guanacastepene A, we found that the stereochemically complex cyclohexene portion of the natural product could be synthesized via an intermolecular Diels-Alder. Therefore recent efforts have been directed towards the pursuing a more convergent intermolecular Diels-Alder/ conjugate addition/ Dieckman condensation strategy towards guanacastepene A.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Enantioselective catalysis; Guanacastepene; Intramolecular Diels-Alder; Nitrones; Organocatalysis
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • MacMillan, David W. C.
Thesis Committee:
  • Stoltz, Brian M. (chair)
  • Grubbs, Robert H.
  • MacMillan, David W. C.
  • Dougherty, Dennis A.
Defense Date:29 September 2003
Author Email:wsjen (AT) alum.mit.edu
Record Number:CaltechETD:etd-10282003-135857
Persistent URL:http://resolver.caltech.edu/CaltechETD:etd-10282003-135857
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:4278
Collection:CaltechTHESIS
Deposited By: Imported from ETD-db
Deposited On:30 Oct 2003
Last Modified:26 Dec 2012 03:07

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