Organic electrochemistry: mechanisms and synthetic applications

Organic synthesis is essential for developing economical, sustainable, and environmentally compatible reaction pathways, which are crucial in medicinal chemistry, pharmaceutical development, and materials science. Electrochemistry, introduced by Faraday in the 19th century, played a pivotal role in organic chemistry but lost prominence in the 20th century, largely replaced by dipolar chemistry characterized by complex and less sustainable processes. With the growing focus on sustainability, electrochemistry has experienced a resurgence, enabled by recent technological advancements that offer more efficient, selective, and sustainable synthetic methods. This PhD thesis investigates electrochemistry as a tool for achieving organic syntheses that are challenging with traditional methods, encompassing three main projects. Project I: The study of NHC-Ag(I) complexes as catalysts in the Borono-Minisci reaction focuses on the functionalization of N-heterocycles, essential in pharmaceuticals. These complexes enhance catalytic efficiency and are easily recyclable. Using cyclic voltammetry, the catalysts were characterized, and the Ag(I)/Ag(II) redox potentials were analyzed, revealing the relationship between complex structure and reaction yield. Project II: A novel electrochemical methodology for the side-chain decarboxylation of Asp and Glu was developed, enabling the synthesis of unnatural amino acids (UAAs) with electron-rich heteroaromatics. These UAAs are critical for protein research and pharmaceutical applications. The optimized method demonstrated high versatility in synthesizing complex UAAs. Project III: An innovative electrophotocatalytic method for direct amide bond formation utilizes FeCl3 as a catalyst, activated through hydrogen atom transfer (HAT) photocatalysis and radical-polar crossover mechanisms. This process eliminates the need for sacrificial oxidants, resulting in a sustainable, selective, and efficient approach for late-stage functionalization of complex molecules. Its scalability in flow systems enhances productivity, making it highly promising for industrial applications, particularly in pharmaceutical synthesis.