Remote-Substituent-Directed Metalations of Arenes

The review covers various metalation reactions of aromatics, which cannot be regarded purely as common ortho-directed metalations (DoM). In the past decade there has been an increased interest and, accordingly, there has been a number of reports about long range electronic effects as they frequently increase the rate of ortho-metalation. Sometimes they are even able to redirect an appropriate metalating agent to a remote position irrespective of an existing ortho activation. Such remote-substituent-directed metalations can be rationalized in terms of through-bond electronic activation, which typically act in conjunction with specific steric (buttressing) effects. A different class of remote-substituentdirected reactions constitute through-space induced metalations where the lithiation site is located close to the directing group. We hope that our review will stimulate further research in this relatively still (with respect to the DoM-based transformations) unexplored area, which is, however, of a great synthetic potential and importance.