Synthesis and Structure of Neopentyl Sodium: A Hydrocarbon-Soluble Reagent for Controlled Sodiation of Non-Activated Substrates.

Abstract

While recent studies have shown that organosodium reagents can offer excellent promise in organic synthesis, their widespread applications can be hindered by their limited solubility in organic solvents, lack of stability, and uncontrolled reactivity. Improving this immature area, here we report the structure of unsolvated neopentyl sodium, which exhibits a unique discrete tetrameric motif and good solubility in hexane. Combining spectroscopic and crystallographic studies with computational bonding analysis, key insights into its constitution and stability have been gained. Expanding its synthetic potential, supporting neopentyl sodium with Lewis donor PMDETA (N,N,N',N″,N″-pentamethyldiethylenetriamine) allows for the direct metalation of challenging non-activated arenes and alkenes, including the regioselective meta-functionalisation of selected 1,3-disubstituted alkyl arenes. Shedding light on sodium-mediated metalation protocols, key organometallic intermediates have been isolated and structurally defined, which can subsequently be intercepted with CO2 or a boron electrophile to be directly used in Pd-catalysed Suzuki cross coupling reactions.