Alkyllithiums are among the most reactive reagents synthetic chemists use. They’re reliable nucleophiles, lithiating reagents, and initiators of anionic polymerization. But because of their inherent reactivity, the conventional chemical wisdom is that it is impossible to make alkyllithiums that contain electrophilic groups. Such reagents would react with themselves long before they could react with anything else. Overturning that long-held belief, a team led by Kyoto University’s Aiichiro Nagaki and Suzuka College’s Jun-ichi Yoshida has found a way to make alkyllithiums that bear electrophilic groups, including epoxides, esters, and cyano moieties (Angew. Chem., Int. Ed. 2019, DOI: 10.1002/anie.201814088). To accomplish this feat, the researchers create and use the alkyllithiums using flash chemistry in a flow microreactor system. Controlling the temperature and time the alkyllithium reagent spends in the section of the reactor where it is formed (known as the residence time) is critical to the method’s success. To create an alkyllithium that contains a cyano group and get it to react with an aldehyde (shown), the chemists had to build a reactor that allowed them to conduct the reaction at –80 °C and limit the alkyllithium’s residence time to 3.4 ms. The researchers predict that their findings will “open a new world of organolithium chemistry.”
This story was updated on Feb. 13, 2019, to correct the alkyllithium's residence time.