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
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|
|Thesis Availability:||Public (worldwide access)|
|Defense Date:||4 September 2009|
|Default Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Diane Carrera|
|Deposited On:||31 May 2011 23:29|
|Last Modified:||26 Dec 2012 04:28|
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