Pyrroles oxazine synthesis

Oxazine, dihydroin pyrrole synthesis, 4, 346 Oxazine, perhydro-polymers, 1, 291... 

The 3-chloro-l,7-dimethylpyridazino[3,4-(7][l,3]oxazine-4,5-dione (149) was prepared in a four-step synthesis starting with (Z)-methyl-3-(3,6-dichloro-l-methyl-4-oxo-l,4-dihydropyridazin-5-yl)-2-methylacrylate (146) which is converted with sodium azide into the 6-azido compound (147). Heating in o-dichlorobenzene at 150°C results in cyclization to methyl 3-chloro-l,6-dimethyl-4-oxo-1,4-dihydro(7//)pyrrolo[2,3-c]pyridazine-5-carboxylate (148) via a nitrene intermediate. Ozonolysis effects ring-enlargement of the pyrrole ring into the 3-chloro-l,7-dimethylpyridazino[3,4-d][l,3]oxazine-4,5-dione (149) (Scheme 26) <79JHC1213>. 

A novel pyrrole synthesis has been developed from 1,2-oxazines <05S3346>. The cycloaddition between nitroso dienophile 45 and 2,3-dimethylbutadiene gave 1,2-oxazine 46. Cleavage of the N-0 bond followed by an oxidative cyclization gave pyrrole 48. 

Hetero Diels-Alder reactions of nitrosoalkenes, e.g. a-nitrosostyrene, with electron-rich alkenes lead to 5,6-dihydro-4H-l,2-oxazines. The cycloadducts are obtained with excellent selectivities. These reactions proceed smoothly under mild reaction conditions at room temperature in the absence of Lewis acids. Oxazines are useful precursors for the synthesis of pyrroles and y-lactams. 

---