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

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.