Exotic alkyllithiums in a flash

Abstract

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 s...