2- -oxazine with sodium

H)-oxazine with sodium borohydride, 51, 25 a-Phenylcyclopropane, 52, 32 1-Phenylcyclopropanecarboxal-dehyde, from 2-benzyl-4,4,... 

Numerous tetrahydro- 1,3-oxazines have been prepared by Meyers et al.2-3 by reducing 5,6-dihydro-4//-l, 3-oxazines with sodium borohy-dride. Catalytic hydrogenation of 5,6-dihydrooxazine-6-one failed to produce the tetrahydro derivative, as ring opening occurred.58... 

Reduction of a spiro compound, dodecahydro-3,3 -bi-l//,3//-pyrido[l,2-c][l,3]oxazine, with sodium amalgam in acetic acid led to reductive cleavage of one of the two tetrahydro[l,3]oxazine rings [71LA(753)27]... 

Other Carbohydrate-based Methods. N-Hydroxy-l,4-dideoxy-l,4-imino-arabinitol, 77, has been prepared in nine steps from ( )-3-0-benzylglyceral-dehyde. A transketolase mediated reaction was used to establish a pentulose (5-0-benzyl-D-xylulose) with correct absolute stereochemistry, and a 1,2-oxazine was the unexpected product of the acid-catalysed reaction of an aldehydic intermediate with triethylorthoformate (Scheme 15). Reduction of this oxazine with sodium cyanoborohydride in acetic acid, did not effect cleavage of the N-O bond, and yielded the iV-hydroxypyrrolidine as a single diastereoisomer. ... 

Dioxotetrahydro-l,3-oxazine derivatives (24) can be obtained by reacting jS-hydroxy acids with sodium cyanate to form a urethane derivative (23) followed by the action of thionyl chloride. ... 

Another reaction leading to a 2,6-diketo derivative of 2,3-dihydro-l,3-6// -oxazine (48) consists in acting with sodium hypochlorite on maleic imide. ... 

N-Substituted 5,6-dihydro-2//-1,2-oxazines were found to be significantly more stable than their N-unsubstituted analogs and could be distinguished from the corresponding 4H isomers using H NMR spectroscopy. Thus, it was shown that oxazinium salt 80 isomerizes on treatment with sodium carbonate to tricyclic... 

Oxazines During the hydrogenolysis of an unsaturated oxazine ring the double bond was also hydrogenated (Scheme 4.146). With sodium amalgam, the double bond was not saturated.545... 

Reduction of the Oximino Fragment in Substituted 5,6-Dihydro-4H-Oxazines Catalytic hydrogenation of substituted dihydro-477-oxazines (552), as well as their reduction with sodium cyanoborohydride (553), were studied in sufficient detail and were used in several total syntheses. However, the use of silylation of six-membered cyclic nitronates enables the synthesis of previously unknown dihydrooxazines containing functionalized substituents at the C-3 and C-4 atoms from easily available precursors. 

Ring closure to the 5//-tetrazolo[5,l-t][l,3]oxazine skeleton has been reported by Hoornaert and co-workers <1996T8813>. These authors treated variously substituted 2,4-dichloro[l,4]oxazin-2-ones 133 with sodium azide. The fused tetrazoles 135 obtained were formed via the formation of their azide valence bond isomer intermediate 134. A similar approach proved to be suitable for the benzologues of these compounds. Thus, the benzoxazinone compounds 136 gave the tricyclic ring-closed tetrazoles 137. Both reactions yielding 135 and 137 proceeded in high yields (80-90%). 

Synthesis of a C(8)-C(18) segment of the larger fragment of lb using the same basic strategy is depicted in Scheme 25. Here, hydroxy ketone 176 was subjected to syn-selective (dr of crude product=90 10) reductive amination [42] with sodium cyanoborohydride and benzylamine followed by tetrahydro-oxazine formation using aqueous formaldehyde. The resulting heterocycle 182 was then converted to unsaturated ester 184 by successive desilylation, oxidation, and entirely (Z)-selective Horner-Wadsworth-Emmons olefination. Re-... 

Oxazine derivatives are formed from unsaturated AAs. Vinylglycine, after epoxidation at the double bond, yielded methyl l,3-oxazin-2-one-4-carboxylate after treatment with sodium methoxide or p-chlorophenol (90TL2291). Similarly, some alkenes react with methyl a-methoxyhippurate and cyclization occurs with BF3-Et20 (75TL3737). In sulfuric acid butyro-lactones are formed. 

N-Methylation of 139 with iodomethane in nitromethane afforded 2,3,4,4,6-pentamethyl-5,6-dihydro-4/7-oxazi-nium iodide 140. Deprotonation of 140 with sodium hydride resulted in formation of the cyclic ketene-A, 0-acetal derivative tetrahydro-l,3-oxazine 141 (Scheme 21) <2006JC0262>. 

Tetrahydro-l,4-oxazin-2-ones can be deprotonated and then reacted with electrophiles. Thus, for example, the nonlabeled analog of compound 81 was deprotonated at the 3-position with sodium hexamethyldisilazide and ethylated using ethyl iodide. The reaction was performed in a 1 10 mixture of hexamethylphosphoramide (HMPA) and tetrahydrofuran <1998T10419>. If a dihalide is used and the oxazine has a free 4-nitrogen, cycloalkylation can be achieved as shown in the reaction of 219 to give 220 (Equation 17) <1993LA477>. 

Deprotonation of the enantiomerically pure AT-to-f-butoxycarbonyl-5,6-diphenyl-2,3,5,6-tetra-hydro-4//-l, 4-oxazin-2-onc (4) with sodium hexamethyldisilazanide at —100 °C with subsequent alkylation of the enolate with active halides gave good yields of 6 and with high diastereoselec-tivity91. Attempts to deprotonate 4 with bases other than sodium or lithium hexamethyldisilazanide effected only decomposition and no trace of alkylation. 

Treatment of 6-chloro-l-(3-hydroxypropyl)-4-phenyl-l,2-dihydropyridin-2-one with sodium methylate in boiling methanol afforded 8-phenyl-2,3,4,6-tetrahydropyrido[2,l-h][l,3]oxazin-6-one [78GEP2731982 79JAP(K)79/ 05997 81BRP1588166,81USP4284778],... 

Ring expansion of isoxazolium salts (168), by treatment with sodium hydroxide, can be used to synthesize both 2H- 1,3-oxazines and 2H- 1,3-benzoxazines. The reaction probably involves an ylide intermediate (Scheme 59) (62CJC882). 

Meyers et al.221-222 showed that tetrahydro-l,3-oxazines exist in tautomeric ring-chain forms [Eq. (62)]. When a 5,6-dihydro-l,3-oxazine is reduced to a tetrahydro-l,3-oxazine, some 3-aminoalcohol can also be formed through the reduction of the open-chain imino form [cf. Eq. (62)]. To avoid this the reduction should be carried out with sodium borohydride at - 40°C. 

The scope of the synthesis was extended by using a 2-vinyloxazine, which led to the formation of propionaldehyde derivatives.227 Another modification of the aldehyde synthesis started with quaternary salts that were treated with sodium hydride, alkylated, then reduced with sodium borohydride to tetrahydro-l,3-oxazines.229... 

---