Oxazinones—

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>. 

A general type of [3 + 3] heterocyclization involves initial nucleophilic attack on the electrophilic three-membered heterocycle by a 1,3-electrophile-nucleophile. Aziridines (330) with either a-mercapto ketones (329) or with a mixture of a ketone and sulfur give 5,6-dihydro-1,4-thiazines (330 — 331 — 332). Azirines (333) can be used for the preparation of pyrazinones (334) from ot-amino esters R2CH(NH2)C02Et and of 1,4-oxazinones from a-hydroxy esters (83TL1153). 

Reacting hydroxylamine with the corresponding trichloro derivative (462) under acidic conditions gave an oxazinone (463) while under basic conditions the 2-isoxazoline (464) was produced (80ZC19). 

In an approach to the AB rings of rubrolone 65, Boger examined the use of oxazinones as a replacement for triazines. Reaction of l,3-oxazin-6-one 66 with enamines 67 produced the corresponding pyridines 70. The reaction proceeds in a manner analogous to the triazines however, instead of losing nitrogen, these systems lose CO2 via the intermediate bicyclo[2.2.2]octanes 68. The resultant 69 then loses pyrrolidine as in the triazine example. 

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). 

In a departure from the prototype molecule, the benzylpiperi-done is first converted to the corresponding aminonitrile (a derivative closely akin to a cyanohydrin) by treatment with aniline hydrochloride and potassium cyanide (126). Acid hydrolysis of the nitrile affords the corresponding amide (127). Treatment with formamide followed by reduction affords the spiro oxazinone... 

A recent variation of these reactions uses 6/f-l, 3-oxazin-6-ones as the electron-deficient heterodiene in place of the triazine.113114 With cyclopropene at — 35 C oxazinone 45 furnishes the 4//-azepine 46 in excellent yield. Likewise, with 3-methylcyclopropene the 4-methyl derivative 46 (R = Me) is formed. Cycloaddition with 1-methylcyclopropene, however, generates a mixture of 7-tert-butyl, 2-methyl 3-methyl- and 5-methyl-4//-azepine-2,7-dicarboxylate in a 2 1 ratio and a 97 % overall yield. 

A few heterocyclic imines reacted poorly if at all with chromium alkoxycarbene complexes. Oxazines required the use of the more reactive (and less stable) molybdenum alkoxycarbenes, producing oxacephams in -40% yield. Oxazo-lines gave low yields (-12%) of the oxapenam system, along with similar amounts of oxazinone, resulting from incorporation of two equivalents of ketene (Eq. 3) [20]. 

CBz-protected benzimidazole gave primarily oxazinone [31], while 3/f-indoles incorporated two equivalents of imine (Eq. 4) [32]. In these cases it appears that the initially formed zwitterionic ketene-imine adduct could not close, and reacted with additional photo activated carbene or substrate. 

Keywords furans, pyrroles, thiophenes, phospholes, oxazoles, pyrones, pyr-idones, oxazinones, high pressure... 

Oligomers Oppolzer s camphor sultam (see also camphor derivatives) Organometallics Organosilicon Organosulfur Organozirconocenes Orthoquinodimethanes Oxabutadienes Oxanorbornadiene(s) Oxazinolactams Oxazinones Oxazoles... 

This homoenolate methodology has been extended to the use of nitrones 170 as electrophiles [72]. Scheldt and co-workers have shown that enantiomerically enriched y-amino esters 172 can be prepared with excellent levels of stereocontrol from an enal 27 and a nitrone 170 using the NHC derived from triazolium salt 164 (Scheme 12.37). The oxazinone product 171, formally a result of a [3-1-3] cycloaddition, is cleaved to afford the y-amino ester product 172. The reaction shows broad substrate scope, as a range of substituted aryl nitrones containing electron donating and withdrawing substituents are tolerated, while the enal component is tolerant of both alkyl and aryl substituents. 

Methyl-8-(2-chlorophenyl)-3,4-dihydro-177,877-pyrido[2,l-f][l,4]oxazine-7,9-carboxylate was obtained by cyclization of l,4-dihydropyridine-3,5-dicarboxylate 338 in the presence of 3M HC1 <1997CAP2188071>. Mild catalytic hydrogenation of oxazinone 339 over 5% Pd/C catalyst afforded 3,4-diphenyl-9-hydroxyperhydropyrido[2,l-f][l,4]oxazin-l-one via sequential iV-carbobenzyloxy (fV-Cbz) deprotection and reductive amination <1998TL3659>. 

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 ... 

Chiral oxazinone-derived nitrone (16), being of particular interest as a prototype for the synthesis of y-oxygenated a-amino acids, reacts with alkenes (D2) efficiently and with high stereoselectivity, to give cycloadducts (489) (Scheme 2.239) (73). 

Synthesis of (—)-monatin (524), a high-intensity sweetening agent, was achieved by chelation-controlled cycloaddition of chiral oxazinone-derived nitrone (16 ) to allyl alcohol (520) in the presence of MgBr2 OEt2 (Scheme 2.248) (746). 

There are several reports dealing with the use of tetrahydropyrrolo[l,4]oxazinones derived from natural proline or prolinol as chiral auxiliaries for the synthesis of enantiomerically pure compounds. The preparation of the heterocycle is described in Scheme 33 (Section 11.11.7.4). The presence of a rigid bicyclic skeleton allows stereoselective introduction of different substituents. The final ring opening of the system (generally by hydrolysis) provides enantiomerically pure compounds with the possibility of recycling the starting chiral auxiliary. 

The oxazinones 74 and 79, already described as chiral glycine templates in Section 11.11.6.3, have been prepared by the PET cyclisation of 252 by irradiation in the presence of 1,4-dicyanonaphthalene as the electron acceptor and methyl viologen as electron-transfer mediator. When the reaction was carried out under strictly anhydrous conditions, compound 79 was isolated, whereas when the reaction was carried out in wet MeCN, compound 74 was the exclusive product (Scheme 33). In any case, the products were obtained with high stereoselectivity, which is the condition required to use them as chiral auxiliaries <2000EJ0657>. 

The crystal structure of the tricyclic triazolo[ 1,5-3] [ 1,2]oxazinone 52 was determined by Begtrup et al. <2002T2397>. This compound was obtained as a product of a designed ring-closure reaction, and it was the X-ray analysis that provided a firm support for the outcome of the transformation. 

Sharp less et al. also reported <2001AGE2004> the synthesis of one representative of the present class of compounds. In their studies on click chemistry, the substituted cyclohexyltriazole 302 was prepared, which, upon treatment with a base at reflux temperature, underwent lactonization to yield the fused oxazinone 303 in high yield. 

Oxazinone (411) was reacted with the carbanion of diethyl malonate to give (substituted amino)phenylmethylenemalonate (412) (86MI1). 

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