Pyridines, pivaloylamino-, lithiation

Pivaloylamino-5-methoxypyridine has been selectively acylated and alkylated in the 4-position by successive reaction with n-butyl-lithium and an electrophile. The activating effect of a A -pivaloylamino- (NHCOBu ) or a methoxy-group alone failed to give orf/to-lithiation. A new general route to nitroso-substituted heterocycles, particularly useful when direct nitrosation is inapphcable, as in the case of pyridine, is illustrated in Scheme 16. 

Alternatively, conversion of 365 to 2,6-bis(pivaloylamino)pyridine 367 via lithiation with n-butyllithium followed by treatment with N-formylmor-pholine 368 and hydrolysis of the latter produces 366 in 67% overall yield (Scheme 80) (93JOC6625). 

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