Reaction Development and Mechanistic Studies of Hydroamination and Hydroamidation of Unactivated Alkenes

The following dissertation discusses the development of iridium catalysts for the intermolecular Markovnikov hydroamination and hydroamidation of unactivated alkenes, as well as mechanistic studies of these transformations. These reactions involve the addition of N–H bonds from nitrogen donors, including 2-aminopyridines and carboxamides, to unactivated terminal and internal alkenes. The reactions occur with high regioselectivity to install amino/amido substituents at the subterminal position of aliphatic chains, either by direct hydroamination of terminal alkenes or by alkene isomerization followed by hydrofunctionalization selective for terminal alkenes. Experimental mechanistic studies, including the synthesis and reactivity of discrete organoiridium complexes, together with computational analysis, provide insights into the elementary steps that control C–N bond formation, alkene isomerization, and catalyst speciation in these transformations.Chapter 1 provides an overview of the synthesis and reactivity of late-transition-metal amido complexes, particularly those of Group 9–11 metals, with unsaturated compounds. This chapter summarizes common methods for preparing metal amido complexes and discusses their reactions with alkenes, alkynes, and polarized multiple bonds, with emphasis on pathways relevant to catalytic reactions to form C–N bonds.Chapter 2 discusses mechanistic studies of iridium-catalyzed hydroamination of unactivated alkenes with 2-aminopyridines. Well-defined hydridoiridium(III) amido complexes were synthesized and shown to undergo migratory insertion of terminal alkenes with unusual selectivity into Ir–N bonds rather than Ir–H bonds at low temperatures. These results reveal how chelation by aminopyridines to the iridium facilitates productive C–N bond formation and suppresses alkene isomerization.Chapter 3 discusses the development of iridium-catalyzed hydroamidation of unactivated alkenes with carboxamides and the discovery of an unexpected rate acceleration by Lewis acidic additives. This regio-convergent reaction forms N-alkyl amide products from terminal or internal alkenes through alkene isomerization followed by selective hydroamidation of terminal alkenes with a range of carboxamides and alkenes. The high efficiency of this catalyst enables the use of lower alkene loadings than those required in prior methods, and enhances the synthetic utility of this transformation. Mechanistic studies suggest that Lewis acidic additives promote catalysis by accelerating ligand exchange from coordinatively-saturated iridium amide resting species to reactive intermediates.