Over the past 15 years, there has been a profound interest in the asymmetric catalytic activation of reactants through hydrogen bonding interactions. The development of additional hydrogen-bond donor catalyst scaffolds is expected to greatly expand the classes of reactions that can be rendered enantioselective, and would also lead to improvements in the effectiveness and substrate-scope of other reactions. To this end, two design principles have been explored: 1) Larger H-H distances (via Deltic Ureas), and 2) Increased acidity and solubility (via Thiosquaramides). A detour was taken to explore cycloaddition reactions encountered while exploring another class of HBD scaffolds (bispyridiniums). The first part of this dissertation (Chapter 1) describes the catalysis of formal [4+2] and [2+2+2] cycloaddition reactions of siloxy alkynes and 1,2-diazines, and of a formal [2+2] cycloaddition reaction of cyclohexenone and siloxy alkyne. While the use of copper(I) and nickel(0) complexes leads to the formal [4+2] cycloaddition product, the use of pyridinium salts provides access to the formal [2+2+2] cycloaddition adducts instead. Metal catalysts based on earth abundant metals are not only as competent as the previously reported Ag(I) salt, but the copper catalyst, in particular, promotes the formal [4+2] cycloadditions of pyrido[2,3-d]pyridazine and pyrido[3,4-d]pyridazine, enabling a new synthesis of quinoline and isoquinoline derivatives. The second part of this dissertation (Chapter 2-3) elaborates upon the synthesis and application of chiral Deltic Urea and Thiosquaramide scaffolds as dual hydrogen-bond donor catalysts. Various approaches towards accessing the highly strained Deltic Ureas have been described, and we also report the first synthesis of, cross-substituted, chiral, bifunctional Deltic Ureas. Their applicability towards the enantioselective catalysis of a Michael reaction is being demonstrated. More acidic than their oxosquaramide counterparts, and significantly more soluble in non-polar solvents, Thiosquaramides are also being demonstrated as excellent catalysts for the enantioselective conjugate addition reaction of barbituric acids to nitrostyrenes. In the final chapter (Chapter 4), the use of Bordwell’s method of overlapping indicators to determine the acidity of select Deltic Ureas and Thiosquaramides has been described.




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