ON THE DISCOVERY OF DIRECT ORTHO-MAGNESIATION

Metalation of 2,4-dicyanocubanecarboxamide (4) with lithium tetramethylpiperidide (LiTMP) followed by quenching with CO2 is non-regioselective and results in carboxylation at the 3 (--> 5) and 6 (--> 6) positions. However, when the reaction was repeated with LiTMP pre-treated with more than 0.5 equivalent of MgBr2, only 6 was produced. This was shown to occur by direct, regiospecific ortho-magnesiation by the bases BrMgTMP and MgTMP2. This initial observation of ortho-magnesiation has opened the way to wide application of this new methodology, a valuable and useful complement to ortholithiation.