Group (IV) Metal-Catalyzed Direct Amidation Synthesis and Mechanistic Considerations

Abstract: The amide unit constitutes the backbone of proteins, and it is present in a large number of pharmaceutically active molecules, polymeric materials such as nylon and Kevlar, as well as in food additives like aspartame. Amides are produced in enormous amounts every year, thus, environmentally friendly and selective methods for their formation are of great importance. This thesis deals with the direct formation of amides from non-activated carboxylic acids and amines with the aid of group (IV) metal complexes. Water is the only by-product of this environmentally benign process. This fact stands in contrast to the most common methods for amide formation to date, which involve the use of waste-intensive, expensive and often toxic coupling reagents. The catalytic protocols presented herein use titanium, zirconium and hafnium complexes under mild reaction conditions to produce amides in good to excellent yields. Furthermore, carbamates are demonstrated to be suitable sources of gaseous amines for the formation of primary and tertiary amides under catalytic conditions. In addition, preliminary results from on-going mechanistic investigations of the zirconium- and hafnium-catalyzed processes are presented.