We now depend heavily on robotic automation, backed by analytical instruments, in our reaction discovery program. Through the automation of repetitive synthetic manipulations and reaction analysis, our screening program in search of new catalysts has been greatly accelerated. More recently, fast robotic screening enabled the discovery of much more practical conditions for the osmium-catalyzed aminohydroxylation reaction. As our molecular diversity objectives continue to broaden, the need for novel and better catalytic reactions will certainly intensify. Therefore, it is reasonable to assume that many important biologically active compounds remain undiscovered.
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 2. 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 that is now ready for the click chemistry addition of a variety of nucleophiles.