Metalation and Alkylation of 3,6-Dihydrothiazine 1-Oxides Prepared via Diels-Alder Cycloadditions of N-Sulfinyl Dienophiles

Article abstract of DOI:10.1021/jo00001a068

The deprotonation of various 3,6-dihydrothiazine 1-oxides using LDA or methyllithium has been investigated.It was found that the stability and chemistry of these lithiated heterocycles are highly dependent upon the nature of the ring nitrogen substituent.Thus, N-alkyldihydrothiazine oxides can be metalated at C-6 to give species postulated as 9, which undergo predominantly anti alkylation with alkyl halides.Alternatively, with MeOD, 9 is deuterated at C-6 primarily in a syn mode.N-Silylated heterocycles ring open rapidly and stereoselectively upon metalation to give dienic sulfinamides like 19, which can be reclosed to the starting dihydrothiazine oxides.N-Phenyl-substituted 3,6-dihydrothiazine 1-oxides upon metalation give mixtures of pyrroles and N-S bond cleavage products.Attempts to generate the dianion from NH dihydrothiazine oxide 17 led only to low yields of C-4 alkylated products with alkyl halides.