How to Develop Organometallic Catalytic Reactions in the Pharmaceutical Industry

Abstract

From a careful analysis of the recent literature, it seems clear that many transition-metal-catalyzed processes used in API synthesis are developed without resorting to any kind of kinetic analysis. Even acknowledging that some of these processes were developed for early development projects and did not need to be thoroughly optimized, the lack of kinetic work is surprising. This Perspective suggests that, in addition to the utilization of modern technologies such as high-throughput experimentation (HTE) and classical optimization tools such as Design of Experiments (DOE), a modest level of kinetic analysis is necessary to develop truly effective catalytic reactions. We offer some basic theoretical considerations and suggest some rather simple tools which can be employed to integrate kinetic analysis of catalytic steps into API development.