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Development of enantioselective organocatalytic technologies for the alpha-functionalization of aldehydes and ketones

Citation

Beeson, Teresa Diane (2008) Development of enantioselective organocatalytic technologies for the alpha-functionalization of aldehydes and ketones. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-05262008-115504

Abstract

The development of an expeditious and room-temperature conversion of aliphatic aldehydes to chiral terminal epoxides is described. α-Chloroaldehydes were prepared via asymmetric enamine catalysis with an imidazolidinone catalyst followed by in situ reduction and cyclization to generate the terminal epoxide. Epoxides with a variety of aliphatic groups and functionalities were produced in 75 minutes with good yields and excellent selectivities.

The catalytic enantioselective direct α-fluorination of aldehydes and ketones is also reported. α-Fluoroaldehydes were conveniently prepared via enamine catalysis with an imidazolidinone catalyst and N-fluorobenzenesulfonimide (NFSI) as an electrophilic fluorine source. The method tolerated a wide variety of aldehyde substrates and functional groups. Catalyst loadings as low as 1 mol% generated the fluorinated products in good yield and excellent enantioselectivity. Additionally, various catalyst architectures were studied to apply the α-fluorination reaction to ketone substrates. Cinchona alkaloid-derived catalysts were found to successfully facilitate the α-fluorination of ketones in high yields and excellent enantioselectivities.

Also presented is the advent of SOMO catalysis, a new mode of organocatalytic activation based on the catalytic generation of radical cations. A secondary amine catalyst reacts with an aldehyde to transiently generate an enamine that, in turn, undergoes a single-electron oxidation to yield a stabilized radical cation that is subject to enantiofacial discrimination. While the parent enamine reacts only with electrophiles, the radical cation combines with SOMO nucleophiles at the same reacting center, thereby enabling a diverse range of previously unknown asymmetric transformations. As a first example and proof of principle, the development of the direct and enantioselective α-allylation of aldehydes using SOMO catalysis is described.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:allylic alkylation of aldehydes
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Awards:The Herbert Newby McCoy Award, 2008
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • MacMillan, David W. C.
Thesis Committee:
  • Tirrell, David A. (chair)
  • Dougherty, Dennis A.
  • Rees, Douglas C.
  • MacMillan, David W. C.
Defense Date:18 April 2008
Record Number:CaltechETD:etd-05262008-115504
Persistent URL:http://resolver.caltech.edu/CaltechETD:etd-05262008-115504
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5203
Collection:CaltechTHESIS
Deposited By: Imported from ETD-db
Deposited On:02 Jun 2008
Last Modified:01 May 2013 18:15

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