The ability to control absolute stereochemistry is a powerful tool in organic synthesis. Given the utility of enantiopure molecules in a number of industries, the pharmaceutical perhaps most prominent, many research efforts have focused on asymmetric catalysis. Recently, the Toste Group has developed and implemented a chiral anion phase-transfer strategy to achieve high enantioselectivity in a number of transformations. This thesis describes new reactivity discovered within this manifold and also discusses the design and synthesis of new phase-transfer catalysts to improve enantioinduction.

Chapter 1 details an asymmetric aminocyclization reaction of tryptamine derivatives enabled by chiral anion phase-transfer of aryldiazonium salts. The immediate products, C3-diazenated pyrroloindolines, can be converted directly to cyclotryptamine natural product derivatives, providing an efficient entryway into a complex scaffold that has been previously accessed by much longer synthetic sequences.

Chapter 2 is a natural extension of the work presented in Chapter 1 and describes an enantioselective α-amination of activated ketone derivatives, again employing aryldiazonium salts as aminating reagents. Obtaining high enantioselectivity initially proves to be very difficult, as use of our traditional library of BINOL-derived chiral phosphoric acids leads to poor enantioinduction. Eventually, we overcome this challenge through the design and synthesis of a new library of chiral phosphoric acids, specifically those derived from a 1,1′-binaphthyl-2,2′-diamine (BINAM) backbone. Chapter 2 also presents potential advantages of our methodology over more commonly used α-amination reactions that utilize dialkyl azodicarboxylates.

Chapter 3 discusses the use of aryldiazonium salts in a more traditional role as cross coupling electrophiles. By merging chiral anion phase-transfer and palladium catalysis, we report an enantioselective Heck-Matsuda arylation of cyclic olefins. Through the process of reaction optimization, we observe counterion dependent reactivity and are ultimately able to avoid the formation of undesired olefin isomers by judicious choice of phosphate. While chiral anions have almost exclusively been used to optimize enantioselectivity, this result indicates that counterions can also be used to modulate chemical reactivity in transitional metal catalyzed processes.