Scaleable Preparation of Functionalized Organometallics via Directed Ortho Metalation Using Mg- and Zn-Amide Bases

A range of aryl and heteroaryl organometallics are efficiently prepared in THF via directed ortho metalation by using the previously reported amide bases tmpMgCl·LiCl (tmp = 2,2,6,6-tetramethylpiperidyl), tmp₂Mg·2LiCl and tmp₂Zn·2MgCl₂·2LiCl. These metalation reactions are carried out at 80−100 mmol scale. The unsaturated organometallic compounds undergo smooth reactions with various electrophiles, e.g. additions to carbonyl groups, Pd-catalyzed cross-coupling reactions or Cu-catalyzed acylations. In all cases, the metalation rates have been compared with corresponding small-scale reactions (1−2 mmol). Moreover, a procedure for the recovery of the valuable tmp-H from the aqueous layer is reported.