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Type of Document	Dissertation
Author	Brown, Sean Pomeroy
URN	etd-02242005-174252
Persistent URL	http://resolver.caltech.edu/CaltechETD:etd-02242005-174252
Title	Iminium and enamine activation: methods for enantioselective organocatalysis
Degree	PhD
Option	Chemistry
Advisory Committee	Advisor Name Title Linda C. Hsieh-Wilson Committee Chair David W. C. MacMillan Committee Member Dennis A. Dougherty Committee Member Nathan Saul Lewis Committee Member
Keywords	catalysis enantioselective organocatalysis imidazolidinone proline
Date of Defense	2005-02-22
Availability	unrestricted
Abstract 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.
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