The Merck Center for Catalysis is a state-of-the-art facility at Princeton University featuring a robotic system that allows for the rapid set-up, monitoring and characterization of thousands of reactions. Opened in 2006 with funding from Merck, the facility has more than 300 chiral organocatalysts available for new reaction screening. These novel catalysts are portioned into 96-well plates that are ready for use in reaction discovery and optimization.
The instrument is equipped to weigh out powdered reagents or administer solutions as desired. Its encapsulation inside a glovebox enables researchers to easily run air and moisture sensitive reactions under an inert atmosphere. Reaction analysis is facilitated by GC-MS analysis, which identifies molecular weights of reaction products that may be further elucidated through advanced software that suggests possible chemical structures. Stir plates are also specially outfitted to allow for irradiation by light emitting diodes (LEDs) for the evaluation of photoredox reactions, a burgeoning area of organic synthesis.
A 2011 Science publication by the MacMillan group illustrated the power of this high-throughput strategy to discover a new reaction, an α–amino C–H arylation, coining the phrase “accelerated serendipity.” The researchers evaluated a large number of random reactions from a designated substrate pool, quickly identified promising reaction products then optimized the new bond forming reaction.
Generous support from Merck has made possible the discovery of myriad new reactions for the synthesis of valuable bioactive compounds. The reactions include an iminium catalyzed conjugate addition, an enantioselective α-arylation of aldehydes, a photoredox catalyzed enantioselective α-alkylation of aldehydes and an enantioselective organocatalyzed fluorination of cyclic ketones.