Regioselective monometalation of 2,5-pyridinedicarboxamides with (2,2,6,6-tetramethylpiperidino)magnesium chloride (TMPMgCI)

The 2,5-pyridinecarboxamides 9–15 were synthesized in one or two steps from diester 1 by addition of an excess of dimethylaluminium amide or successive addition of two different dimethylaluminium amides with or without intermediate workup. For the carboxamides 16 and 17 this method failed; they were, however, available by other procedures. Metalation of the carboxamides 9–17 with TMPMgCI and subsequent reaction with electrophiles led to the 2,3,5- and 2,4,5-substituted pyridines 9a/b-17a/b, 18 and 19 with regioselectivities ranging from predominant 4-substitution to complete 3-substitution.