Selective Zincation of 1,2-Dicyanobenzene and Related Benzonitriles in Continuous Flow Using In Situ Trapping Metalations

Abstract

A mild and general metalation procedure for the functionalization of 1,2-dicyanobenzene and related polyfunctionalized benzonitriles using a commercially available continuous flow setup is reported. The addition of TMPLi (TMP = 2,2,6,6-tetramethylpiperidyl) to a mixture of an aromatic substrate with a metallic salt such as ZnCl2 under appropriate conditions (0 °C, 20 s) leads to fast in situ lithiation of the arene followed by transmetalation with ZnCl2 to afford the corresponding functionalized arylzinc compound that were trapped with various electrophiles in high yields. The reaction scope of these in situ trapping metalations in flow is broader and needs less equivalents of the base and the metal salt than the corresponding batch procedure.