Indolo benzoxazines

Japanese researchers varied aryl substituent at C-4 in nitronate (147), LA, and the reaction conditions, they used successfully diastereomerically pure nitronates (147) (Scheme 3.121) for the synthesis of various fused-ring systems, such as benzofuro-[3,2-d]-l,2-oxazines (322), furo-[3,4-d]-isoxazoles (323—326), indolo-[2,3-b]-l-pyrroline 1-oxides (327), 4//-1,2-benzoxazines (328), benzofuro-[2,3-c]-tetrahydropyrans (329), and monocyclic 1,2-oxazines (330). 

Methyl [6aRS-(6aa,9p,10aP)]-4,6,6a,8,9,10a-hexahydro-7-methyl-7H-indolo[3,4-g,h][l,4]benzoxazine-9-carboxylate hydrochloride ... 

A mixture of 33.5 g of manganese dioxide and a solution of 8.4 g of the product of Step 5 in 840 ml of methylene chloride was stirred under an inert atmosphere for 16 hours and was filtered. The filtrate was washed and evaporated to dryness under reduced pressure. The residue was added to a few ml of ether and the mixture was vacuum filtered. The product was dried to obtain 2 crops of 3.9 and 0.91 g of methyl [6a-RS (6aa,9p,10ap)]-4,6,6a,8,9,10a-hexahydro-7-methyl-7H-indolo[3,4-g,h][l,4]benzoxazine-9-carboxylate melting at 174°C and an additional 1.1 g of product melting at 174°C by chromatography of the mother liquors. 

A solution of 9.5 g of tosyl chloride in 125 ml of pyridine was added to a mixture of 6.6 g of the product of step 7 and 66 ml of pyridine and the mixture was stirred at 20°C for 17 hours and was then poured into methylene chloride. The mixture was washed with aqueous saturated sodium bicarbonate solution, dried and evaporated to dryness. The residue was chromatographed over silica gel and was eluted with a 95-5 methylene chloride-methanol mixture to obtain 7.7 g of [6aRS-(6aa,9p,10aP)]-4,6,6a,8,9,10a-hexahydro-7-methyl-7H-indolo[3,4-g,h][l,4]benzoxazine-9-p-toluenesulfonate-methanol which after crystallization from an isopropyl ether-methylene chloride mixture melted at 180°C. 

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