A facile synthesis of benzo(b)furan derivatives including naturally occurring neolignans via regioselective lithiation of ortho-cresols using the bis(dimethylamino)phosphoryl group as a directing group.

Abstract

A facile synthesis of 2-arylbenzo[b]furans via directed lithiation of ortho-tolyl tetramethylphosphorodiamidates as the key step is described. Lithiation of ortho-tolyl tetramethylphosphorodiamidates at -105°C followed by reaction with aromatic esters and then acidic treatment led to 2-arylbenzo[b]furans in modest overall yields. The utility of this strategy has been demonstrated in regioselective and short syntheses of the naturally occurring neolignans carinatin, eupomatenoid-1, and eupomatenoid-13.