Organolithium Bases in Flow Chemistry: A Review

Flow chemistry is a continually emerging and ever-growing area of synthetic organic chemistry. It provides an orthogonal approach to traditional batch chemistry, oftentimes allowing for more efficient routes to desired target molecules. It is generally accepted that flow chemistry offers a valuable change to the process landscape. From a process perspective, there are many advantages associated with flow chemistry over traditional batch chemistry, the most prominent of which is an increased safety profile with the use of highly reactive chemical species, such as organolithiums. These reagents are highly valuable species for the efficient synthesis of pharmaceutical intermediates. Disadvantageously, use of these reagents on commercial scale is severely hindered by the highly energetic nature of the reaction intermediates and their concomitant safety risk. Flow chemistry provides a viable platform for use of these reagents, offering a high degree of control over reaction parameters. In this review, we present a comprehensive account of the published literature implementing the use of organolithium reagents as strong bases for deprotonation reactions in flow systems.