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Iminium and enamine activation: methods for enantioselective organocatalysis


Brown, Sean Pomeroy (2005) Iminium and enamine activation: methods for enantioselective organocatalysis. Dissertation (Ph.D.), California Institute of Technology.


Further development of an organocatalytic LUMO-lowering activation strategy utilizing chiral imidazolidinone salts has been described. Enantioselective catalytic Friedel-Crafts alkylations of furans and thiophenes have been achieved with good yields and high levels of enantioselectivity. Furthermore, this methodology has been utilized to access enantioenriched a-chiral esters.

The organocatalytic iminium activation strategy has been applied to the development of an enantioselective Mukaiyama-Michael reaction for the construction of the g-butenolide architecture. This reaction is viable due to imidazolidinone catalysts' ability to partition silyloxyfurans to react through an unprecedented 1,4-addition manifold to a,b-unstaturated aldehydes. This Mukaiyama-Michael methodology has also been extended to provide access to a-amino acids by use of silyloxyoxazoles.

Enamine activation of aldehydes has provided the first direct asymmetric a-oxidation of carbonyls. This proline catalyzed HOMO-raising activation strategy affords high levels of reaction efficiency and enantioselectivity. Moreover, the function of proline solubility has been investigated to explain an unusual kinetic and enantioselective profile.

The imidazolidinone framework, developed for iminium activation, was also demonstrated to participate in enamine activation of aldehydes to perform the enantioselective a-chlorination of aldehydes. A first generation catalyst provided good yields and high enantioselectivities at -30 °C. Design of a second generation catalyst afforded high levels of reaction efficiency and enantioselectivity at ambient temperature.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:catalysis; enantioselective; imidazolidinone; organocatalysis; proline
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.
  • Dougherty, Dennis A.
  • Lewis, Nathan Saul
Defense Date:22 February 2005
Record Number:CaltechETD:etd-02242005-174252
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:735
Deposited By: Imported from ETD-db
Deposited On:04 Mar 2005
Last Modified:26 Dec 2012 02:32

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PDF (FinalThesis2.pdf) - Final Version
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