Scaleable Preparation of Sensitive Functionalized Aromatics and Heteroaromatics via Directed Metalation Using tmpZnCl·LiCl

A range of functional aryl and heteroaryl zinc reagents were prepared in THF via directed zincation using the previously reported amide base tmpZnCl·LiCl. These metalation reactions were carried out on 50 mmol scale. Diverse sensitive functional groups such as a nitro group, an aldehyde, an ester, and a nitrile are tolerated. Furthermore, the resulting zinc intermediates show excellent reactivity towards various classes of electrophiles, e.g. Pd-catalyzed cross-coupling reactions or Cu-catalyzed acylations and allylations. In all cases, the metalation rates have been compared with those of the corresponding small-scale reactions (1−2 mmol). Moreover, the recovery of the valuable tmp-H from the aqueous phase has been demonstrated.