Continuous Flow Preparation of (Hetero)benzylic Lithiums via Iodine–Lithium Exchange Reaction under Barbier Conditions

Abstract

Herein we report the generation of benzylic lithiums via an iodine-lithium exchange reaction on benzylic iodides performed in continuous flow using <i>t</i>BuLi as the exchange reagent. The resulting benzylic lithium species are trapped in situ by carbonyl electrophiles under Barbier conditions, resulting in benzylic secondary and tertiary alcohols. This flow procedure further allows the generation of highly reactive heterobenzylic lithium compounds, which are difficult to generate under batch conditions. A general scale-up was possible without further optimization.