Development of Transition-Metal Catalysts for Selective Hydrofunctionalization of Unactivated Alkenes

The following dissertation discusses the development of transition-metal catalysts for selective hydroboration and hydroamination of unconjugated and unstrained alkenes, termed “unactivated alkenes.” These reactions proceed with high levels of enantioselectivity and, for reactions of unsymmetrical internal alkenes, with high regioselectivity.Chapter 1 is an overview of transition-metal-catalyzed hydrofunctionalization of unactivated alkenes. This review focuses on the challenges and strategies for achieving asymmetric hydroamination and hydroboration of unactivated alkenes, particularly unactivated internal alkenes. Mechanistic aspects of these reactions are also discussed. The summary of previous literature precedents highlights how the work described in this dissertation fills knowledge gaps in this field.Chapter 2 describes the development of copper-catalyzed regioselective and enantioselective hydroboration of unsymmetrical internal alkenes. This process, coupled with a series of subsequent stereospecific transformations of the enantioenriched hydroboration products, constitutes a formal hydrofunctionalization that efficiently converts internal alkenes to a diverse set of enantioenriched compounds with distinct functional groups.Chapter 3 describes the mechanistic study of the copper-catalyzed asymmetric hydroboration of alkenes. A comprehensive study by both experiment and computation reveals the fundamental principles that govern the efficiency of the copper catalysts for reactions with alkenes and selectivity observed for the alkene hydroboration.Chapter 4 describes the development of new bisphosphine ligands for asymmetric hydroboration of 1,1-disubstituted alkenes. Trimethylgermanyl groups on the bisphosphine ligand significantly increase enantioselectivity of the hydroboration of 1,1-disubstituted alkenes. In addition, this new set of ligands forms a catalyst that is highly active toward the hydroboration of unactivated 1,2-disubstituted alkenes.Chapter 5 describes the development of copper-catalyzed formal hydroamination of unsymmetrical internal alkenes. Similar to the hydroboration discussed in Chapter 2, the hydroamination occurs with high enantioselectivity and regioselectivity. This work revealed that the polar functional groups proximal to the alkene controlled the regioselectivity through inductive effects.Chapter 6 describes the development of iridium-catalyzed asymmetric hydroamination of unactivated internal alkenes. A combination of a cationic iridium complex and 2-amino-6-methylpyridine, was essential to the development of the hydroamination. This is the first example of a direct, highly enantioselective addition of an N-H bond to an unactivated internal alkene