1,3-oxazine-2-ones, from

The syntheses of simple 1,3-oxazines (74AG596 86G361) from acylated amino acids (86G361) by treatment with dihalotriphenylphosphorane and of heterocondensed l,3-oxazin-4-ones from several N-acylated heterocyclic /3-enamino esters (81CB3188) have been implemented by aza-Wittig reactions of heterocyclic 2-(triphenylphosphoranylidenamino)esters with acid halides. 

Late transition metal-catalyzed processes also proved to be very useful tools for formation of the C-O bond of the 1,3-oxazine ring from the corresponding alkynes. In the presence of 1-5 mol% of a cationic gold(l) complex, A -BOC-protected alkynylamines 450 were converted to 6-alkylidene-l,3-oxazin-2-ones 451 under very mild conditions (Equation 49) <2006JOC5023>. 

The Staudinger reaction of imines 481 derived from 7-oxanorbornenone with arylacetic acid chlorides 482 furnished a 0-40 60-100 mixture of C-2-epimeric, spiro-condensed l,3-oxazin+-one derivatives 483 and 484, the ratio of which proved to depend on the substituents on the aromatic rings and on the nitrogen atom (Equation 54) <2002TL6405>. 

One remarkable process is the photochemical synthesis of 3,4-dihydro-2H-l,3-oxazin-4-ones from a-sulfonyloxy-(3-keto amides (obtained by coupling of P-keto-carboxylic acids with amines, followed by treatment with an iodanyl mesylate). This allows the regioselective oxidation of less-activated C—H bonds and a C—O bond formation which is unusual for a Norrish-Yang reaction [69]. The formation of a 1,6-0—C biradical has been postulated as an intermediate (Scheme 9.42). 

Diastereoselective Synthesis of 2-Oxazoiidinones and Tetrahydro-2//-l,3-oxazin-2-ones from Acyclic vV-AIlyl and A-Homoallyl Carbamates with 1,2- and 1,3-Asymmetric Induction... 

Many ring-fused imidazole derivatives have been synthesized by various methods. Domino Michael addition retro-ene reaction of 2-alkoxyiminoimidazolidines and acetylene carboxylates provided a synthesis of 2,3-dihydroimidazo[l,2-a]pyrimidin-5-(l//)-ones <05T5303>. A single step synthesis of 3,5-dialkyl-9-nitroimidazo[l,2-c]quinazolin-2(3//)-ones from simple carbonyl compounds, primary amines or amino acid methyl esters and 2-azido-5-nitrobenzonitrile has been published <05TL5778>. Diels-Alder reaction of azadienes and benzimidazole-4,7-diones afforded imidazo[4,5-g ]quinoline-4,9-dione derivatives <05EJ01903>. Reaction between isocyanides and dialkyl acetylenedicarboxylates in the presence of 4,5-diphenyl-l,3-dihydro-2//-imidazol-2-one provided a one-pot synthesis of 5//-imidazo[2,l-ft][l,3]oxazine derivatives <05T2645>. Microwave irradiation was employed in the synthesis of 1-ary 1-3-acetyl-1,4,5,6-... 

The optical rotatory dispersion (ORD) curves of the diastereomers of l-(p-nitrophenyl)-3-methylperhydropyrido[l,2-c][l,3]oxazines, obtained from (-)-2-(2-hydroxypropyl)piperidine with p-nitrobenzaldehyde, are nearly mirror images of each other (68CJC1105). The absolute configurations in cyclohexane of the dextrorotatory cw-3,4fl-H-3-phenyl- and trans-3,4fl-H-3-phenylhydropyrido[l, 2-c] [1,3]oxazin-6-ones, containing 3S,AaR and 35,4a5 atoms, respectively, were determined on the basis of the presence of positive Cotton effects (85T2891). 

Similar reactions to those used to obtain l,3-oxazin-4-ones from diazo-l,3-diketones [Section 6.05.6.2.2(iv)] have also been employed to form 2-thioxo-l,3-oxazin-4-ones (e.g. 212), but here diacyldiazomethanes (211) are treated with rhodium(II) acetate and the acylketenes released through loss of nitrogen and the Wolff rearrangement are captured by isothiocyanates (Equation (18)). The products are frequently accompanied by the corresponding 2,4-diones <93BCJ238>. 

Reactions of azines with ketenes 4,5-Dihydro-l,3-oxazin-6-ones from 2 ketene molecules... 

Tetrahydro>l,3>oxazin>2 Ones from oxido- and halogeno-nrethans... 

Oxazolldones and tetrahydro-l,3-oxazin-2-ones from halogenourethans s. 16,404... 

Table 15.27 Carbonylative synthesis of 1,3-oxazin-6-ones from palladium-catalyzed alkenyl C-H bond activation in the enamides. ...

A general rule can be suggested for one of the principal ways of forming 1,3-oxazine derivatives. They can be formed from 1,3-sub-stituted propane derivatives of general formula ... 

One of the most extensively investigated groups of 1,3-oxazine derivatives is the 5-nitro derivatives of tetrahydro-l,3-oxazine. They were first prepared from 1-nitropropane, aqueous formaldehyde, and ammonia by Hirst et and independently by Senkus from other primary nitroparaffins, formaldehyde, and primary amines. Numerous compounds of the general formula (6) were later prepared from primary nitroparaffins. " ... 

Perhydro derivatives of pyrido[l,2-7)][l,2]oxazines are frequently applied in the total synthesis of various alkaloids to control the stereochemistry, and pyrido[l,2-c][l,3]oxazines and [l,3]oxazino[3,4-u]quinolines were also used in the stereoselective syntheses of different alkaloids. Perhydropyrido[l,2-c][l,3]oxazines and their benzologs are formed form 2-(2-hydroxyethyl) piperidines and from their benzologs to justify the stereochemistry of 2-(2-hydroxyethyl) derivatives. Different optically active pipecolic acids can be prepared via 4-phenylperhydropyrido[2,l-c][l,4]oxazin-l-ones. 

Treatment of perhydropyrido[l,2-c][l,3]oxazin-l-ones 83, 85, and 87 with 2M ethanolic KOH afforded 2-(2-hydroxyalkyl)piperidines 84, 86, and 88 (96CJC2434). (4-)-9-Epi-6-epipinidinol (90) was obtained similarly from 3,8-dimethylperhydropyrido[l,2-c][l,3]oxazin-l-one 89 (98T13505). 

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). 

Alkoxy-3-(4-biphenyl)perhydropyrido[], 2-c][], 4]oxazines were obtained from 3-hydroxy derivative with PrOH and Br(CH2)30H in a boiling acidified medium (00JMC609, 00MIP13). Spontaneous dehydration of b-hydroxy-1,3,4,6,7,1 lZ -hexahydro[l,4]oxazino[3,4-n]isoquinolin-4-one 258 in CHCI3 gave 3,4,6,7-tetrahydro derivative 259 (97JOC2080). 

Phenyl-9-(2-propoxycarbonylamino)perhydropyrido[2,l-c][l,4]oxazin-1-one was prepared from methyl 4 phenyl-l-oxoperhydropyrido[2, l-c][l,4]oxazine-9-carboxylate (98MIP12). First, the methyl ester was hydrolyzed into 9-carboxylic acid by heating in 6N HCl, then the carboxylic acid was reacted with (Ph0)2P(0)N3 in benzene in the presence of NEt3 at 22 °C for 45 min, then at reflux for 50 min. After addition of -PrOH the reaction mixture was boiled for 20 h to yield a 9-(iso-propoxycarbonylamino) derivative. 

Irradiation of 4-(3-benzoylpropionyl)-1,4-morpholine (267) yielded an epimeric mixture of 9-hydroxy-9-phenylperhydropyrido[2,l-c][l,4]oxazin-6-ones 268 and 269 via hydrogen abstraction from the position 3 of the morpholine moiety of 267 (98T2529). It was assumed that the steric hinderance between the phenyl group and the hydrogen atoms of 5-methylene group of 267 in the biradicals contributed to the observed selectivity. 

A single isomer of 4-phenylperhydropyrido[2,l-c][l,4]oxazin-l-one 319 was isolated from a reaction mixture of 2-bromocyclohexane and 2-azido-2-phenylethanol. The formation of 319 was deduced from azepino[l,2-i]... 

Trifluoro-2-nitrosopropene can be generated in situ from 1 -bromo-3,3,3-trifluoropropan-2-one 2-oxime. It is a highly reactive nitrosoalkene that readily undergoes cycloaddition with silyl enol ethers and other die-nophiles to give CF3- substituted 1,2-oxazines (92JOC339). 

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