CaltechTHESIS
  A Caltech Library Service

Design and development of new enantioselective catalytic reactions and progress towards the total synthesis of callipeltoside A

Citation

Wiener, John Jacob Moely (2004) Design and development of new enantioselective catalytic reactions and progress towards the total synthesis of callipeltoside A. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-01282004-181526

Abstract

The development of a new enantioselective catalytic anti aldol reaction is described. In this Lewis acid-catalyzed process, a chiral metal-ligand enolate complex is accessed through soft-enolization and reacts with an aldehyde to form aldol adducts in good enantioselectivity and anti diastereoselection. Mechanistic studies confirm the non-Mukaiyama pathway involving a reactive metal enolate species. Investigations have shown that the choice of amine base has a remarkable effect on the mechanism and outcome of the reaction.

The development of the first enantioselective organocatalytic [1,3]-dipolar cycloaddition reaction is also reported. In this imidazolidinone-catalyzed process, nitrones react with a,b-unsaturated aldehydes to form chiral isoxazolidines in excellent yield, enantioselectivity, and diastereoselection. The scope of this process appears quite general with respect to both the nitrone and aldehyde components of the reaction. A second-generation imidazolidinone catalyst offers improved reaction rates and selectivities and has also facilitated the development of the first exo selective organocatalytic [1,3]-dipolar and Diels-Alder cycloaddition reactions.

A synthetic approach towards the marine natural product callipeltoside A is described. The synthesis relies upon rapid construction of the stereochemical backbone through a novel tandem amino-sulfide acyl-Claisen rearrangement. Subsequent elaboration towards the macrolide has involved a highly diastereoselective reductive opening of a spirocyclic intermediate, highly diastereoselective Ireland Claisen rearrangement, and synthesis of the tetrahydropyran moiety through a palladium catalyzed carbonylative cyclization. Completion of the synthesis has yet to be achieved due to difficulties in removal of a benzyl ether protecting group.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:aldol; asymmetric; carbonylation; catalysis; claisen; dipolar cycloaddition; enantioselective; ireland; Lewis acid; macrolide; nitrone; organocatalysis; oznonolysis; spirocycle; spirocyclization; tandem; tandem claisen; total synthesis
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:
  • Hsieh-Wilson, Linda C. (chair)
  • MacMillan, David W. C.
  • Grubbs, Robert H.
  • Marcus, Rudolph A.
Defense Date:20 January 2004
Author Email:jake_wiener (AT) post.harvard.edu
Record Number:CaltechETD:etd-01282004-181526
Persistent URL:http://resolver.caltech.edu/CaltechETD:etd-01282004-181526
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:387
Collection:CaltechTHESIS
Deposited By: Imported from ETD-db
Deposited On:09 Feb 2004
Last Modified:26 Dec 2012 02:29

Thesis Files

[img]
Preview
PDF (01Introduction.pdf) - Final Version
See Usage Policy.

130Kb
[img]
Preview
PDF (02Aldol.pdf) - Final Version
See Usage Policy.

1566Kb
[img]
Preview
PDF (03Dipolar_cycloaddition.pdf) - Final Version
See Usage Policy.

1851Kb
[img]
Preview
PDF (04Callipeltoside.pdf) - Final Version
See Usage Policy.

2345Kb
[img]
Preview
PDF (05Summary.pdf) - Final Version
See Usage Policy.

406Kb
[img]
Preview
PDF (06Appendix.pdf) - Final Version
See Usage Policy.

18Mb
[img]
Preview
PDF (JJMW_thesis.pdf) - Final Version
See Usage Policy.

24Mb

Repository Staff Only: item control page