The central theme of our research has traditionally been the discovery of practical catalytic transformations for organic synthesis. Recently, our focus shifted to the application of these reactions in the synthesis of molecular libraries. Therefore, it is reasonable to assume that many important biologically active compounds remain undiscovered. It is also reasonable to assume that a number of these undiscovered molecules are not structurally complex. Using click chemistry, we have begun to search for these undiscovered domains of biologically relevant molecules.
Versatility is another key characteristic of a click reaction.
An example of a click reaction we have exploited in the successful synthesis of diverse molecular libraries is the addition of heteronucleophiles to epoxides and aziridines. A generalized reaction sequence through which we have synthesized more than 1000 individual compounds is shown in Figure 1. In short, among the approximately infinite candidates of less than 500 amu, we aim to find the gems that are also simple to make. By taking advantage of both the wide array of commercially available, inexpensive olefins and our expertise in olefin oxidations, we can tailor our click chemistry scaffolds. Thus, we use the aminohydroxylation reaction, followed by a dehydrative cyclization, to form the aziridine scaffold, which is now ready for the click chemistry addition of a variety of nucleophiles.