Homodimerization of 3-substituted-2-oxindoles for the construction of vicinal all-carbon quaternary centers: chemical, photochemical and electrochemical approaches

Abstract

Advancements in organic synthesis are revolutionizing the synthesis of complex natural products, which are essential in biomedical research and drug discovery due to their intricate structures. Natural products such as chimonanthine, folicanthine, calycanthine, psychotriadine, etc., with vicinal all-carbon quaternary stereocenters, are particularly significant for their strong binding properties and biological activities. One common feature of these natural products is the presence of dimeric 3-substituted-2-oxindoles having vicinal all-carbon quaternary stereocenters. This review focuses on the chemical, photochemical, and electrochemical approaches for the homodimerization of 3-substituted-2-oxindoles employed by different researchers, with a strong focus on the mechanistic details of proton-coupled electron transfer (PCET). The article also demonstrates that PCET facilitates the reduction of kinetic barriers through the formation of low-energy intermediates and the expansion of synthetic possibilities. Furthermore, natural product syntheses (folicanthine and chimonanthine) from dimeric 3-substituted-2-oxindoles are discussed. Chemical syntheses are time-consuming and, even more importantly, generate significant waste due to the use of metal-based oxidants and catalysts. In this regard, electrochemical synthesis methods offer promising solutions by avoiding the use of chemical oxidants and metal catalysts, thus minimizing environmental impact. The article also outlines the advantages and disadvantages of different synthesis methods and proposes a new direction for future research in this field.