Chiral phosphine-catalyzed asymmetric transformations of allenoates and alkynoates and photoinduced, copper-catalyzed C-N couplings with aromatic nitrogen ceterocycles

Abstract

Chapter 1 describes the development of chiral biphenyl-derived phosphepines and their application as catalysts for an asymmetric [4 + 1] annulation to form functionalized cyclopentenes bearing a non-spirocyclic quaternary stereocenter. Additional studies demonstrate the synthetic utility of the cyclopentene products for further stereoselective functionalization and provide insight into the mechanism of the reaction. Chapter 2 describes the development of photoinduced, copper-catalyzed C-N couplings between aromatic nitrogen heterocycles (i.e., indole, benzimidazole, imidazole, and carbazole) and aryl, alkenyl, and alkynyl halides. These reactions utilize an inexpensive catalyst (Cul, without an additional ligand) and proceed at unusually low temperature for Ullmann coupling processes with these heterocycles (room temperature). Additional studies probe the selectivity of the reaction with respect to both the nucleophilic and the electrophilic coupling partner. Chapter 3 details progress towards developing a method for asymmetric, intermolecular y additions of oxygen nucleophiles to alkynoates using a chiral phosphine catalyst. Conditions are presented that effectively couple alkynoates bearing an aryl substituent at the y position with a variety of alcohols in good yield and high ee. Future efforts will be focused on expanding the scope of this process and conducting experiments to gain insight into the reaction mechanism.