1,2-Oxazinones, formation

A further type of nitro-group rearrangement gives rise to a cyclic hydroxamic ether. Noland e.t aL describe the action of cold, dilute sulfuric acid on the sodium salt of 5-nitronorbornene (98), which results in conversion to the oxazinone (101). This complex rearrangement is rationalized by the sequence 98 101 involving intermediate formation of the nitrile oxide (99) and the hydroxamic acid (100). 

The asymmetric synthesis of (4R,93, 9aR)-4-phenyl-l-trimethylsilyloxy-9-vinylperhydropyrido[2,T ][l,4]oxazine with a high level of stereoselectivity in the cyclization of (3R,5R)-5-phenyl-3-phenylsulfanyl-4-(6-trimethylsilanyl-hex-4-enyl)-2-trimethylsilyloxy-morpholine was rationalized via AMI calculations <1998T10309>. AMI calculations suggested that the formation of l,6-dioxo-l,3,4,6,7,8-hexahydropyrido[2,Tf][l,4]oxazine-9-carboxylates 230 from acroyl chlorides 228 and 1,4-oxazinone 229 is favored over the hetero-Diels-Alder condensation (Equation 45) <1996JOC5736>. 

In agreement with the behavior of ylides 427/441 the pyridinium imine betaines 446 gave rise to the formation of oxazinones 447 on interaction with diphenyl cyclopro-penone274 or its thio analogue275 ... 

In the reaction of the conformationally restricted epoxy alcohol 84 and methyl or benzyl isocyanate, the epoxy carbamate 85 was formed. Cycliza-tion of 85 in tetrahydrofuran in the presence of sodium hydride gave the oxazinone 86 in approximately 20% yield, and the oxazolidinone 87 (R = Me, CH2Ph) in 40-60% yield. The formation of the two products can be rationalized by different nucleophilic attacks on the urethane nitrogen. With increasing nucleophilicity of the nitrogen, the regioselectivity of the reaction is shifted toward the formation of 87 (92TL3009). 

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). 

As with most camphor-based chiral auxiliaries, the size and steric congestion at the C-8 position of the camphor moiety can determine its efficiency. Through the formation of a connection between C-8 and C-2, a novel camphor-based oxazinone auxiliary 29, which can be prepared from camphor in 3 steps,52 becomes highly effective in directing stereoselective aldol reactions (Scheme 5.11).53... 

Dipolar Cycloadditions. Highly substituted proline derivatives can be prepared by removal of the r-Boc protecting group from the oxazinone followed by condensation of the heterocycle with an aldehyde in the presence of p-Toluenesulfonic Acid in benzene. Under these conditions, Schiff base formation and ylide generation occur. Subsequent [3 + 2] cycloaddition with a dipolarophile affords the bicyclic heterocycle, which is then de-protected to yield the desired proline derivative (eqs 10 and 11). ... 

When an amino ester is heated with an anhydride, water and ethanol are lost during the formation of an oxazinone ring. Triphenyl phosphite or dibromotri-phenylphosphorane may be used to cyclize an amino ester. 

Cyclization of iminophosphorane and hydroxy groups with an isocyanate leads to the formation of benzoxazines replacing the isocyanate by carbon dioxide or carbon disulphide gives a good yield of the corresponding oxazinone or oxazinethione. 

The UV spectrum of the tetramethyloxazinium salt (3) (counterion AlCU ) in 0.1 M acetic anhydride-AlCl3 complex in dichloromethane shows a maximum absorption at 270 nm (log e 3.92) <85JA5722>. This has been ascribed to the 7t-7t band and was taken as evidence that the cation is an aromatic ring system. UV spectra were earlier taken as evidence for the formation of aromatic oxazinium cations when 3,5-diphenyl-l,2-oxazinone (12) and related oxazinones are alkylated or protonated (Equation (1)) <73ZORi987, 74ZORi5i3>. For example, the UV spectrum of compound... 

A pyrrolo[l, 4]oxazinone has been prepared by cyclization of the )3-chloroethyl pyrrolecarboxylate anion (231) (Equation (90)) <70FRP1502066>, and a pyrrolo[l,3]thiazinedione (232) by lactam formation (Equation (91)) <87JMC498>. 

The pyrazino[2,l-i][l,3]oxazinium trifluoroacetate (319) is formed in good yield from the pro-tonated pyrazine derivative (318) by intramolecular cycloamination, together with a small amount of the expected Diels-Alder product (Equation (87)) <89T6519>. Saturated pyrazino[2,l-c][l,4]oxazinones (320) and (239) were prepared by lactone formation, in good yields (Equation (88)) <75IJC468, 78MI 825-01 >. 

One of the main problems with this approach is synthesis of the starting bis(halomethyl) helerocycles. Two main routes have been used free radical halogenation of the appropriate bis(methyl) compound (usually using iV-bromosuccinimide) or transformation of the bis(hydroxymethyl) derivative which in turn can be obtained from the corresponding diacid or diester as, for example, in Scheme 13. Lack of selectivity in the formation of the desired dihalo compound can be a problem in the former case. A different approach to bis(halomethyl)pyridines involves cycloaddition of chloroalkylacetylenes to oxazinones (Scheme 15) <96T11889>. 

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