The activation of relatively unreactive carbon-carbon (C-C) multiple bonds is an important tool for the introduction of functional groups and stereochemical information in organic molecules. In recent years, the use of electrophilic cationic gold(I) complexes for the functionalization of alkynes and allenes has seen rapid development. An especially general application of gold catalysis is the nucleophilic trapping of gold-activated ð bond to give a heterocyclic compound. In the case of allenes, chiral ligands have been used to generate product with excellent enantiocontrol. In the first part of this Thesis we report studies on the development of an enantioselective cyclization using the gold-catalyzed transformation of propargyl esters to generate allenes in situ. A subsequent gold-catalyzed dynamic kinetic asymmetric cyclization of a phenol onto the allene resulted in the generation of enantioenriched cyclized chromanone derivatives from racemic starting material. The optimal catalyst for this transformation was a (biscarbene)digold(I) complex, which delivered better enantioselectivities than previously known phosphine-gold and phosphoramidite-gold complexes.

Electrophilic sources of the halogens (fluorine, chlorine, bromine, and iodine) activate C-C multiple bonds in much the same way as gold(I) complexes, but the electrophilic atom of the reagent is incorporated into the final product. Because halogen atoms are amenable to further functional group manipulation and are also present in complex natural products, the enantioselective synthesis of halofunctionalized products from alkenes is an important synthetic goal. Typically, enantioselectivity is achieved using a chiral catalyst to activate the electrophilic reagent. However, high enantioselectivities may be hampered by uncatalyzed background reactivity. The Toste research group has introduced a new approach for electrophilic functionalization (chiral anion phase transfer catalysis) by inducing ion pairing between a phosphate anion chiral source and a cationic electrophilic reagent by phase transfer. This concept was initially demonstrated for fluorination, using the cationic reagent F-TEDA-BF4 (Selectfluor®). In the second part of the Thesis, we report studies on the extension of this strategy to the heavier halogens. With the successful development of bromination and iodination reagents suitable for chiral anion phase transfer, we applied these reagents to the synthesis of halogenated benzoxazines with high levels of enantioselectivity.

Chapter 1 – An overview of the field of ion-pairing and phase transfer catalysis with chiral anions. Discussion and commentary in this chapter is focused on mechanistic details that led to key developments in the field, as well as future directions for areas of research.

Chapter 2 – A regio- and enantioselective bromocyclization of difluoroalkenes to access CF2Br-containing stereocenters was developed. These bromodifluoromethylated heterocycles were derivatized to a number of pharmaceutically relevant difluoromethylene-containing motifs. Additionally, an efavirenz analogue was synthesized, demonstrating the synthetic utility of this methodology. A combination of parameterization and traditional physical organic techniques was used to study the effect of the achiral bromination reagent on the regio- and enantioselectivity of the reaction.

Chapter 3 – An atropselective bromination of scalemic phenols was developed to access brominated compounds with two chiral axes via parallel kinetic resolution. The efficiency of parallel kinetic resolution was explored by using racemic starting materials, whereby one diastereomer of product was obtained in high enantioselectivity.

Chapter 4 – Preliminary reactivity was established for the chlorotetrafluorosulfanylation of aryl boron reagents, which serve as valuable intermediates en route to Ar–SF5 compounds.

Appendix – An automated process for predicting sulfimine stabilities was developed, with applications towards the identification of promising oxaziridines for methionine bioconjugation.

This thesis represents the efforts to develop new catalytic methods, and to discover new organic materials. These efforts were driven by mechanistic thinking in organic and organometallic chemistry.

Chapter 1 offers a historical overview of how mechanistic understandings drive reaction development and inspire the development in other related fields such as chemical biology and materials science.

Chapter 2 discusses a new strategy to activate transition metal complexes by hydrogen-bond donors (HBDs). Anion binding catalysis using HBDs, Au(I)/Au(III) redox chemistry, and the prevalence of anion abstraction in Au(I) catalysis are introduced as a foundational design principle of the new strategy. Attempts to achieve anion abstraction from Au(I) and Au(III) complexes using this strategy are then presented. This led to the development of an enantioselective intermolecular Au(I)-catalyzed hydro(hetero)arylation reaction of allenes. Experimental and computational studies showed an interplay of non-covalent interactions that led to the observed enantioselectivities. Computational studies on the origin of enantioselectivities were conducted in collaboration with ‪Dr. Binh Khanh Mai from Prof. Peng Liu’s lab at University of Pittsburgh.‬‬‬‬‬‬‬‬‬‬‬‬

Chapter 3 focuses on the design and synthesis of cyclic acylsilanes and their applications in ring-opening metathesis polymerization (ROMP). First, photochemical reactivities of acylsilanes and how these reactivities can be translated to macroscopic properties, such as degradability of materials, are discussed. The synthesis of eight-membered-ring acylsilane-based cyclic olefins as monomers for ROMP led to photodegradable polymers. Photochemical ring expansion reactions of the cyclic acylsilane were also discovered. The resulting product holds promise to yield degradable polymers with controlled release properties. This work was done in collaboration with Mufeng Wei, Emma Vargo, and Yiwen Qian from Prof. Ting Xu’s lab at UC Berkeley.

Chapter 4 describes the discovery of a new linker for covalent organic frameworks (COFs), namely nitrone linkages. This was driven by the diverse reactivities of nitrone functionalities. The resulting COFs were found to undergo a photochemical isomerization reaction. This work was done in collaboration with Dr. Daria Kurandina, and Dr. Wentao Xu from Prof. Omar Yaghi’s lab at UC Berkeley.