Hexahydropyrido oxazin-4-one

Irradiation of piperidine 62 in CH2CI2 at concentration of 3mg/ml in the presence of 1-methylimidazole using a high-pressure mercury lamp (150 w) yielded 2-phenyl-4,6,7,8,9,9n-hexahydropyrido[2,l-h][l, 3]oxazin-4-one (01 SI258). 

Perhydropyrido[l,2-A][l,2]oxazines are applied as key intermediates in a stereospecific total syntheses of (-)-pumiliotoxin C and 5-e/ /-pumiliotoxin C(96JCS(P1)1113), and the marine alkaloid)—)-lepadins A, B, C (OOOL2955). (2-Pyridyl)propionic acids 13 can be regioselectively prepared via 2,3,4, 4fl,7,8-hexahydropyrido[l,2-A][l,2]oxazin-2-ones 12 (00OL4007). 

Reaction of tetrahydropyridin-4-one 119 and l,r-carbonyldiimidazole furnished l,3,4,4n,5,6-hexahydropyrido[l,2-c][l,3]oxazine-l,6-dione 120 (99JA2651). Similarly, pyrido[l,2-c][l,3]oxazine-l-one 121 and [1,3] oxazino[4,3-n]isoquinoline-4-one 122 were prepared from the respective 2-(2-hydroxypropyl)piperidine and l-(2-hydroxypropyl)-1,2,3,4-tetrahy-droisoquinoline (99JOC3790). Reaction of a 2 1 diastereomeric mixture of l-(l,2-dihydroxyethyl)-6,7-dihydroxy-l,2,3,4-dihydroisoquinolines 123 and 124 with l,l -carbonyldiimidazole gave a 2.7 1 mixture of 1,9,10-trihy-droxy-l,6,7,ll/)-tetrahydro-2//,4//-[l,3]oxazino[4,3-n]isoquinoline-4-ones 125 and 126, which were separated on preparative TLC plate (99BMC2525). 

Michael addition of dialkyl cuprate reagents to optically active 4-phenyl-l,3,4,6,7,8-hexahydropyrido[2,l-c][l,4]oxazin-l-one afforded stereoselec-tively 9-alkylperhydro derivatives 228 in a mixture Et20 and THF at -40 °C in the presence of Cul in good yields (99TL3699). 

Diels-Alder reactions of (5.S )-5-phenyl-3,4-dehydromorpholin-2-one 388 with 1,3-butadienes 387 furnished (4.S, 9a,S )-/ra r-4,9a-//-4-phenyl-l,3,4,6,9,9a-hexahydropyrido[2,l-f][l,4]oxazin-6-ones 389 (Equation 70) <1996TA2563>. 

A diastereoselective intramolecular hetero-Diels-Alder reaction of optically active 428 gave unstable 1,3,4,8,9,9a-hexahydropyrido[2,l-f][l,3]oxazin-l-one 429 (X = 0), and l,3,4,8,9,9a-hexahydropyrido[l,2-(z]pyrazin-l-one 429 (X = NTs) (Equation 80) <2003JA4970, 2004T10277>. In the case of pyrido[l,2- ]pyrazine, the reaction was carried out in the presence of 2,6-di- /-butyl-4-methylphenol. 

Treatment of 2-methyl-9a-methoxy-4,6,7,8,9,9a-hexahydropyrido[2,l-b][l,3]oxazin-4-one with cone, ammonium hydroxide in a sealed tube gave 2-methyl-6,7,8,9-tetrahydro-4//-pyrido[l, 2-a]pyrimidin-4-one [75H(3)927]. 

Depending upon the reaction conditions, 2-ethoxy-3,4,5,6-tetrahydropy-ridine and isopropylidene 2-acetylmalonate afforded either perhydropy-rido[2,l-h][l,3]oxazine-2,4-dione (162) or hexahydropyrido[2,l-b][l,3]ox-azine-3-carboxylic acid (163) (86MI1). Reaction of 2-methoxy-3,4,5, 6-tetrahydropyridine with diketene without a solvent gave a mixture of 4H-quinazolin-4-one (164) and hexahydropyrido[2,l-h][l,3]oxazin-4-one (165) [75H(3)927]. 

Optically active CM-3,4a-H-l,3,4,4a,5,6-hexahydropyrido[l,2-c][l,3] oxazine-l,6-diones were obtained from (+)-2-(2-hydroxy-2-phenylethyl)-and (+)-2-(2-hydroxypentyl)-l,2,3,4-tetrahydropyridin-4-one with 1,1 -carbonyldiimidazole in THF in the presence of triethylamine (93JA8851, 93JOC5035). 

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