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The development of brønsted acid catalysis technologies and mechanistic investigations therein

Citation

Carrera, Diane E. (2010) The development of brønsted acid catalysis technologies and mechanistic investigations therein. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechTHESIS:06022010-164832965

Abstract

The enantioselective reductive amination of ketones with Hantzsch ester has been achieved through Brønsted acid catalysis. A novel triphenylsilyl substituted BINOL-derived phosphoric acid catalyst has been developed for this transformation, imparting high levels of selectivity when used with methyl ketones and aromatic amines. A stereochemical model for the observed selectivity based on torsional effects has been developed through molecular modeling and is further supported by a single crystal x-ray structure of an imine-catalyst complex. Mechanistic studies have revealed the importance of catalyst buffering and drying agent on reaction efficiency while a Hammett analysis of acetophenone derivatives offers insight into the key factors involved in the enantiodetermining step. Kinetic studies have shown that imine reduction is rate-determining and follows Michaelis-Menten kinetics. Determination of the Eyring parameters for the imine reduction has also been accomplished and suggests that the phosphoric acid catalyst behaves in a bifunctional manner by activating both the imine electrophile and the Hantzsch ester nucleophile. The intermolecular addition of vinyl, aromatic, and heteroaromatic potassium trifluoroborate salts to non-activating imines and enamines can also be accomplished through Brønsted acid activation. This analog of the Petasis reaction shows a wide substrate scope and is amenable to use with a variety of carbamate protected nitrogen electrophiles in the first example of metal-free 1,2-additions of trifluoroborate nucleophiles. The mechanistic underpinnings of benzyl trifluoroborate addition has also been explored and, in contrast to what is seen with π-nucleophilic species, appears to proceed through an intramolecular alkyl-transfer mechanism.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Bronsted acid, organocatalysis, asymmetric synthesis, organotrifluoroborate
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:
  • Barton, Jacqueline K. (chair)
  • Dervan, Peter B.
  • Stoltz, Brian M.
  • MacMillan, David W. C.
Defense Date:4 September 2009
Record Number:CaltechTHESIS:06022010-164832965
Persistent URL:http://resolver.caltech.edu/CaltechTHESIS:06022010-164832965
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5908
Collection:CaltechTHESIS
Deposited By: Diane Carrera
Deposited On:31 May 2011 23:29
Last Modified:26 Dec 2012 04:28

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