Exploring the Reactivity of Copper Towards the Synthesis of Reactive Carbonyl Electrophiles

Carbonylation represents an atom economical approach in which inexpensive CO is used as a C1 feedstock. In recent years, transition metal-catalyzed carbonylative couplings have been studied extensively. Among various transition metals, copper has emerged as a sustainable alternative due to its relative abundance and inexpensive and non-toxic nature. The unique reactivity of copper has been used to develop various carbonylative C-C and C-X bond-forming reactions with alkyl halides previously. Although strong nucleophiles were required to reduce the alkyl electrophiles under copper catalysis conditions, the scope of weak nucleophiles remains unexplored. The first part of the thesis focuses on the synthesis of potassium acyltrifluoroborates (KATs), for which a copper-catalyzed carbonylative borylation method of synthesis was recently reported. KATs are an important class of compounds with immense applications in bioconjugation, polymer, and materials chemistry. This study represents a more straightforward synthesis of KATs than the previous method by mediating coupling between mixed anhydrides of abundant carboxylic acids and commercially-available B2(pin)2 in the presence of a commercial copper catalyst and subsequent quenching by aqueous KHF2. This method provides a broad scope, including important amino acid-derived KATs. The later parts focus on the scope of weak nucleophiles such as carbonates and fluorides in carbonylation reactions. We hypothesized that the weak nucleophiles would have lower reduction potential to activate the alkyl halides, and hence would require photoactivation. When carbonate base was employed under photocatalytic conditions, carboxylic acid anhydrides were obtained, whereas acyl fluorides were synthesized with fluoride base. Mechanistic studies indicated a general mechanism for both the transformations involving heterogeneous copper(0)-mediated radical carbonylation pathway. Further extension of this method resulted in a new reactivity, delivering very important tetralone derivatives when the amine base was used, allowing internal aromatic groups to act as Freidel-Crafts nucleophiles.