Generation and Reactions of Pyridyllithiums via Br/Li Exchange Reactions Using Continuous Flow Microreactor Systems

A continuous flow microreactor method for generating and carrying out reactions on pyridyllithiums has been developed based on Br/Li exchange reactions of bromopyridines and dibromopyridines. The reactions can be carried out without using cryogenic conditions by virtue of short residence times and efficient heat transfer, while very low temperatures such as –78 or –110°C are required for conventional batch macro methods. Moreover, sequential introduction of two different electrophiles has been successfully achieved using dibromopyridines in an integrated flow microreactor system composed of four micromixers and four microtube reactors.