Tetrahydro-2//-l,3-oxazine-2-one

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... 

In a similar way, 2-oxazolidinones and tetrahydro-2//-l, 3-oxazin-2-ones have been prepared by the reaction of primary allyl amines and homoallyl amines10, respectively, with carbon dioxide and iodine in methanol via an intramolecular cyclization. Prolonged reaction for a week in the presence of cesium carbonate increases the yield to 70-90%. This reaction has a large applicability and the ease of the method makes it useful in organic synthesis. 

The /rflm -/V-silylated tetrahydro-2//-l, 3-oxazin-2-one 27 (R = TBDMS) has been utilized in the synthesis of (+ )-negamycin (28)15, a compound which shows a strong inhibitory activity against Gram-negative bacteria. 

The halocyclization of a homoallylic carbamate 718, containing (S)-l-phenylethylamine as chiral source, similarly affords a 50 50 diastereomeric mixture of tetrahydro-2//-l,3-oxazin-2-ones 8, which can be easily separated by chromatography and identified by 1 H-NMR spectroscopy. In compounds 8, the substituent at C-6 displays a strong tendency to occupy the equatorial position in both isomers. 

Diastereoselective Synthesis of 2-Oxazolidinones and Tetrahydro-2//-l,3-oxazin-2-ones... 

The addition of 0.1 equivalents of allylpalladium chloride dimer and 0.3 equivalents of triphen-ylphosphane to the reaction mixture results in a significant rate enhancement and increased yield, however, the corresponding tetrahydro-2//-l,3-oxazin-2-ones are obtained in a 1 1 diastereomer-ic ratio. 

The A -acyl derivatives of 4-substituted-3,4,5,6-tetrahydro-27/-l,3-oxazin-2-ones proved to behave as effective chiral auxiliaries in asymmetric enolate alkylations and aldol reactions, the stereoselectivities of which were found to be higher for 4-isopropyl than for 4-phenyl derivatives <2006OBC2753>. The transformations of 4-isopropyl-6,6-dimethyl-3-propa-noyl-3,4,5,6-tetrahydro-2/7-l,3-oxazin-2-one 251 to 252 or 253 proceeded with excellent diastereoselectivities (Scheme 47). 6,6-Dimethyl substitution within the oxazine ring facilitated exclusive exocyclic cleavage upon hydrolysis of the C-alkylated and the aldol products 252 and 253, to furnish a-substituted carboxylic acids 254 or a-methyl-/ -hydroxycarboxylic acids 256. 

Lithium aluminum hydride reduction of tetrahydro-l,3-oxazin-2-ones 434 results in the corresponding A -methyl-substituted 1,3-amino alcohols 435 (60JA4656 87TL1623). 

Bromopropylamine was reported to form tetrahydro-l,3-oxazin-2-one in moderate yield when treated with the carboxylating reagent (O2 /C02) formed by the electrochemical reduction of oxygen in acetonitrile in the presence of carbon dioxide <1997JOC6754>. 

Maytansine 588 is a macrocyclic tetrahydro-l,3-oxazin-2-one derivative isolated from higher plants, mosses, and an actinomycete, kctinosynnema pretiosum. Despite the extraordinary antitumor activity found for many maytansine derivatives, the Phase II clinical trials with maytansine turned out to be disappointing. The chemistry and biology of maytansinoids have recently been reviewed <2004CPB1>. 

The Rh-catalyzed reaction of isoxazolidine 240 at 150-170 °C and65atmofCOgave tetrahydro-l,3-oxazin-2-one 241 in good yields, wherein the insertion of CO took place selectively into the N-O bond of isoxazolidine (Scheme 34). 

Breslow94 introduced an interesting method of forming 2-oxo compounds, which was based on his earlier work.95 Thermolysis of n-octadecyl azidoformate gives some tetrahydro-l,3-oxazin-2-one (23) [Eq. (14)]. 

Farrissey and Nashu105 reported that the reaction of an epoxide with phenyl isocyanate, which previously had been claimed to yield a tetrahydro-l,3-oxazin-2-one,1,106 produced, in fact, a 2-oxazolidone derivative. 

The usefulness of this method was demonstrated by the synthesis of tetrahydro-6-iodomethyl-4-methyl-3-(l-phenylethyl)-2tf-l,3-oxazin-2-ones (12). Of the four possible isomers, only those in the tram configuration are formed, which are the more stable for this type of compound. Analysis of the coupling constants for H-6 and H-4 shows that for both isomers the substituent at C-6 is in the equatorial position and the methyl on C-4 in the axial position, probably because the methyl at C-4 is forbidden to lie in the equatorial position due to steric hindrance exerted by the bulky substituent at nitrogen17. 

Tetrahydro-l,3-oxazin-2-ones can be used to prepare enantiomerically pure amino alcohols. The starting materials can be prepared through the nonselective iodocyclization of homoallylic... 

Tetrahydro-l,3-oxazin-2-ones may be obtained through the palladium-catalyzed carbonylation of 3-aminopropanols <86JOC2977>, but despite these innovations more traditional methods for the syntheses of perhydro-1,3-oxazines are still used for example, the cyclization of 3-aminopropanols with ethyl chloroformate, phosgene, or similar reagents <76BAP447>. The preparation of the cor-... 

Tetrahydro-l,3-oxazin-2-ones (368) can be obtained by the reaction of arylthiols with N-bromo-A-cinnamylcarbamates (367). Presumably a sulfenyl bromide, or its equivalent, is formed initially which then acts as an electrophilic agent to promote the cyclization step (Equation (44)). However, should sulfenyl chlorides be reacted with A-alkyl-A-cinnamylcarbamates (369) then the regioselectivity is changed and oxazolidinones (370) are formed instead (Equation (45)) <86JPR173>. 

The tetrahydro-l,3-oxazin-2-one (372) is prepared through the cyclization of the threo form of hydroxycarbamate (371) in contact with mesyl chloride, conversely the erythro isomer is O-sulfinated without undergoing cyclization. The removal of an A-Boc group under basic conditions is unusual, and it is proposed that the selective cyclization of the threo isomer occurs because, in its lowest energy conformation, the proximity of the ethoxycarbonyl group and the mesyloxy unit potentiates the ionization of the latter. Once formed, the mesyloxy anion assists deprotonation of the Boc group and hence the cyclization to the oxazine (Scheme 100) <87H(26)64i, 88H(27)667>. 

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

Functionalization of methyl groups Tetrahydro-l,3-oxazin-2-one ring from azidoformic acid esters... 

Reduction of 3-substituted-3,4,7,8-tetrahydro-l//,6//-pyrido[l,2-t][l,3 oxazin-l-ones with NaBHjCN in boiling MeOH, and with NaBH4 in AcOH, afforded 4a-epimeric mixtures of perhydro derivatives <2005T1595>. 

Treatment of tert-butyl (2/. )-2-(2-propcny lidene (piperidine-1-carboxylate with McjSil and PhOH yielded 3-substituted-3,4,7,8-tetrahydro-l//,6//-pyrido[l,2-c][l,3]oxazin-l-ones <2005T1595>. Reaction of l-(benzoxycarbonyl)2-styrylpiperidin-4-one with I2 resulted in the formation of r-3,4a-//-/ra r-4-//-4-iodo-3-phenylperhydropyrido[l,2-d-[l,3]oxazine-l,6-dione <2002JOC1972>. A diastereomeric mixture of 3-iodomethylperhydropyrido[ 1,2 z [ 1,3]oxazin-l-ones (e.g., 178) was obtained by intramolecular iodocarbamation of l-(alkoxycarbonyl)-2-allylpiperidines (e.g., 177) with I2 (Equation 34) <1999JOC8402, 2002OL3459>. 

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