Dearomative Alkylation of Heteroarenium Salts via Blue-Light Enabled Homolytic C-C Bond Cleavage

Abstract

Partially and fully saturated nitrogen heterocycles are frequently present in pharmaceuticals and natural products. One approach towards synthesis of such molecules is dearomatization. Dearomatization enables the use of feedstock aromatic compounds towards the synthesis of substituted non-aromatic heterocycles. Cross-electrophile couplings (XECs) offer an alternative approach to the traditional cross-coupling reactions by enabling the direct coupling of two electrophiles. XECs avoid the synthesis of nucleophiles and offer a better functional group tolerance. A common drawback of XECs is cross-selectivity. Since both coupling partners are electrophiles, this often leads to the formation of homo-coupling side-products. The main focus of this dissertation is the study of the reversible homodimerization of heteroarenium salts. Heteroarenium salts are prone to homodimerization under reductive conditions. The formed heteroarene dimers are proposed to go through a blue light enabled homolytic C—C bond cleavage, resulting in the formation of carbon-centered radicals. This process enables the use of heteroarene dimers as radical reservoirs. Chapter 2 shows extensive mechanistic studies on the C—C bond cleavage, followed by their use in alkylation of various heteroarenium salts via alkyl iodides and activated alkyl bromides. Chapter 3 extends the scope of the coupling to simple alkyl bromides and carboxylic acids. Chapter 4 discusses three future directions: enantioselective synthesis of dihydroisoquinolines, dearomative synthesis of pyrans, and synthesis of N-aryl pyridinium salts.