Introducing Water and Deep Eutectic Solvents in Organosodium Chemistry: Chemoselective Nucleophilic Functionalizations in Air
Giuseppe Dilauro, Cosimo Luccarelli, Andrea Francesca Quivelli, Paola Vitale, Filippo Maria Perna, Vito Capriati
Abstract
Abstract Advancing the development of perfecting the use of polar organometallics in bio‐inspired solvents, we report on the effective generation in batch of organosodium compounds, by the oxidative addition of a C−Cl bond to sodium, a halogen/sodium exchange, or by direct sodiation, when using sodium bricks or neopentylsodium in hexane as sodium sources. C( sp 3 )‐, C( sp 2 )‐, and C( sp )‐hybridized alkyl and (hetero)aryl sodiated species have been chemoselectively trapped (in competition with protonolysis), with a variety of electrophiles when working “on water”, or in biodegradable choline chloride/urea or L‐proline/glycerol eutectic mixtures, under hydrous conditions and at room temperature. Additional benefits include a very short reaction time (20 s), a wide substrate scope, and good to excellent yields (up to 98 %) of the desired adducts. The practicality of the proposed protocol was demonstrated by setting up a sodium‐mediated multigram‐scale synthesis of the anticholinergic drug orphenadrine.