UC Berkeley

The following dissertation discusses the development of ruthenium and iridium catalysts for the intermolecular hydroamination of unstrained and unconjugated alkenes with amines. These reactions involved the direct addition of the N–H bond of derivatives of 2-aminopyridine to unactivated terminal alkenes and the remote addition of the N–H bond of derivatives of 2-aminopyridine to unactivated disubstituted alkenes. These reactions occurred with high chemo- and regioselectivity to install the amino group at the subterminal position of an aliphatic chain. Experimental and computational mechanistic studies have shed light on the mechanism of these reactions and common side pathways during catalytic hydroamination.

Chapter 1 provides an overview of the hydroamination of alkenes catalyzed by late transition metals. This review includes information regarding the importance and the challenges of catalytic hydroamination, representative examples of catalytic hydroamination of different classes of alkenes, including vinylarenes, conjugated dienes and trienes, strained alkenes as well as unactivated alkenes, and the mechanisms of those reactions. Discussion of photocatalytic hydroamination of alkenes and the future of catalytic hydroamination is also included in this chapter.

Chapter 2 describes the development of ruthenium-catalyzed hydroamination of unactivated terminal alkenes. A cationic ruthenium complex catalyzes the intermolecular hydroamination of a variety of unactivated terminal alkenes with 2-aminopyridine as an ammonia surrogate. Detailed mechanistic studies show that this reaction occurs by a new mechanism comprising initial formation of an imine by oxidative amination, followed by reduction of the imine.

Chapter 3 describes the development of iridium-catalyzed enantioselective hydroamination of unactivated terminal alkenes. A combination of a specific iridium precatalyst containing a monodentate, labile ethylene ligand and NaBArF catalyzes enantioselective hydroaminations with equimolar amounts of a 2-aminopyridine and unactivated alkenes containing a wide range of functional groups. This catalytic system suppresses competing side reactions, such as the isomerization of the terminal alkene and the racemization of the product of hydroamination.

Chapter 4 describes the development of iridium-catalyzed remote hydroamination of unactivated disubstituted alkenes to place the amino group at the unactivated subterminal carbon of an alkyl chain. The electronic properties of the substituent on the aminopyridine and the development of a new ligand are critical to the high regioselectivity and reaction rates of the reaction.