Dihydro-27-l,3-oxazines

Berkessel and co-workers extended the synthetic applicability of hydrogenbonding thiourea catalyst 78 in the DKR of azlactones to the kinetic resolution (KR) of structurally related, but configurationally stable 4,5-dihydro-l,3-oxazine-6-... 

Alkaline hydrolysis of of 5,6-dihydro //-l,3-oxazines is a convenient method via which to obtain the corresponding 1,3-amino alcohols or their A -acyl derivatives <1996CC1629>. The yields are usually excellent, as in the transformation of 2,4,4-trimethyl-5,6-dihydro //-l,3-oxazine 130 to 3-amino-3-methylbutan-l-ol 131 (Equation 11) <2001JLR265>. 

The ring-opening reactions of l,3-oxazin-6-ones with nucleophiles or electrophiles both result in / -amino acid derivatives. Methanolysis of 2-phenyl-4,5-dihydro-l,3-oxazin-6-one 206 under very mild conditions gave methyl 3-(benzoylamino)propionate 207 (Equation 19) <20030L1575>. 

The asymmetric alcoholytic ring opening of 4-substituted-2-phenyl-4,5-dihydro-l,3-oxazin-6-ones proved to be a efficient method for the preparation of enatiomerically pure /3-amino acid derivatives <2005AGE7466>. Treatment of 2,4-diphenyl-4,5-dihydro-l,3-oxazin-6-one 208 in the presence of the bifunctional chiral thiourea catalyst 211 resulted in formation of an enantiomerically enriched mixture of the unchanged oxazinone (iJ)-208 and allyl (4)-3-benzoyl-amino-3-phenylpropanoate 209. The resolved material (iJ)-208 and the product 209 could easily be separated by a selective hydrolytic procedure that converted oxazinone (iJ)-208 quantitatively into the insoluble iV-benzoyl /3-amino acid 210 (Scheme 37). 

BKC115>. Amides derived from aromatic carboxylic acids and benzotriazole were reported to form 2-aryl-5,6-dihydro-4//-l,3-oxazines with 3-aminopropanol in excellent yields when subjected to microwave irradiation in the presence of SOCI2 <2004JOC811 >. Imidates have often been applied to cyclize 1,3-amino alcohols directly to 5,6-dihydro-l,3-oxazine derivatives <1996ACS922, 2004JHC69, 2004JHC367>. 

Aryl-4,5-dihydrooxazoles 556 underwent cobalt-catalyzed carbonylation to give 4,5-dihydro-l,3-oxazin-6-ones 557, usually in good yields, but an exception was the ring enlargement of 556 containing a 5-methyl (R = Me) or a sterically bulky 2-(o-tolyl) substituent (Equation 67) <20030L1575>. 

Trimethylsilyloxyfuran (274) reacts with ethoxycarbonylnitrene to give 3-ethoxycarbonyl-3,4-dihydro-l,3-oxazin-2-one (276) via aziridine intermediate (275) (89TL5025). 

Acylketenes are also employed in a number of other routes to dihydro-l,3-oxazin-4-ones. Isocyanates or isothiocyanates often form the second component of the reaction, and the approaches then differ only in the way the acylketene is generated (Scheme 95). 

Monosubstituted malonyl chlorides can also be used to obtain 3,4-dihydro-l,3-oxazine-2,4-diones. Ziegler et al.1B reported the formation of 53 by heating benzylmalonyl chloride with phenyl isocyanate [Eq. (41)]. By carrying out the reaction in the presence of stannic chloride, the temperature can be considerably lowered.185 Mono-... 

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. 

Thermolysis of 5,6-dihydro-l,3-oxazines, e.g. (36), gave A-allylamides (RCONHCH2CH=CH2) in good yield.152158... 

Dihydro-l,3-oxazines are usually reduced by borohydrides2,3 reasons for some failures have been discussed.229 Catalytic hydrogenation led to ring opening.58... 

Oxo-2-thiono-3,4-dihydro-l,3-oxazine rearranges188 into the 2,4-dioxo-l,3-thiazine (95) [Eq. (74)]. 

Also cyclization of a six-membered chain has been reported. By brominating nonconjugated allylic amides, McManus et a/.165 166 obtained 5,6-dihydro-l,3-oxazine derivative in addition to two other compounds (a five-membered ring and the brominated amide) [Eq. (32)]. 

Chloromethyl-5,6-dihydro-l,3-oxazines react with aryl Grignard reagents, giving ultimately an arylacetic acid.249 Quaternary salts of 5,6-dihydro compounds also furnish carboxylic acids.240... 

The same cyclization of allylic O-methylisoureas provides imidazolines or 5,6-dihydro-l,3-oxazines (when catalyzed by benzeneselenenyl triflate).3... 

C26H NO 19957-52-9) see Clomifenc (-)-cri-2,4-diphcnyl-5-( 1 -ethoxy ethoxy )-4,5-dihydro-l,3-oxazin-6-onc... 

Perhydro derivatives (270) are prepared from 1-substituted 1,4,5,6-tetrahydro-pyrimidines which form cycloadducts with epoxides (70LA(742)128). 4H-5,6-Dihydro-l,3-oxazines and -thiazines react in the same way to form products of type (270) (66AG(E)875). 

Aryl-4,5-dihydrooxazoles 380 undergo cobalt-catalyzed carbonylation to give 4,5-dihydro-l,3-oxazin-6-ones 381, generally in good yields (Scheme 177) <20030L1575>. 

Dihydro-l,3-oxazin-4-ones 375 are obtained from various enamines 374 and benzoyl isocyanate in contrast, trichloroacetyl isocyanate is reported to give only the azetidinone 376 (equation 154)27. 

Many centres with a formal positive charge on nitrogen have already been described, especially with polymerizations of more or less exotic monomers. 4,5-Dihydro-l,3-oxazine is transformed to polymer by the overall reaction... 

Malone. G.R.. and Meyers. A.I., The chemistry of 2-chloromethyl-5,6-dihydro-l,3-oxazines. Grignard coupling metalation studies. A synthesis of a-chloro aldehydes and arylacetic acids, J. Org. Chem., 39. 618. 1974. 

Dihydro-l,3-oxazine is transformed to polymer by the overall reaction... 

Prepared by condensation of 2-benzyl-4,4,6-trimethyl-5,6-dihydro-l, 3-oxazine (Columbia) with paraformaldehyde catalyzed by trifluoroacetic acid. 

Benzyl alcohol, 100, 150 Benzyl chloride, 297 6-Benzyl-9-ethyladenine, 126 Benzylic add rearrangement, 193 Benzylideneazine, 57 Benzylidene dichloride, 148-149 Benzyltriethylammonium chloride, 19 2-Benzyl-4,4,6-trimethyl-5,6-dihydro-l, 3-oxazine, 284... 

Dihydro-l, 3-oxazin-4-ones. 5.2.8 l,3-Oxazine-2,4(3H)-diones Reduction... 

Related work has shown that acylated Meldrum s acids (170 R = alkyl or aryl) react with imines to give a mixture of l,3-oxazine-4,6-diones (171) and 2,3-dihydro-l,3-oxazin-4-ones (172) plus smaller amounts of the acids (173) (Scheme 47). The diones (171) are unstable and if they are heated in separate experiments they ring-open and recyclize to afford the oxazin-4-ones (172) <87CPB1860>. 

An intramolecular version of this type of reaction has already been described in Section 6.05.6.2.2(iii) for the synthesis of 4//-l,3-oxazines, and an analogous route to dihydro-1,3-oxazines has also been reported. Thus, treatment of the (Z)-isomer (194) of l,l-di(A-benzoylamino)oct-6-ene with boron trifluoride diethyl etherate in DCM affords the bicyclic 5,6-dihydro-l,3-oxazine... 

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