1.2- oxazepines synthesis

A 1,3-oxazepine derivative (158) has been isolated in low (2-3%) or unspecified yield by treatment of the Z-ketovinylazirine 157 with diiron nonacarbonyl50 or molybdenum hexacarbonyl,51 respectively (Scheme 182) the major products of these reactions are pyrrole derivatives (see Scheme 23 in Section IV,A,1). There is no preparative value in this type of oxazepine synthesis (Scheme 182) since the transformation can be affected efficiently in a thermal reaction at 100°C.52... 

Scheme 4.23 Oxazepine synthesis by copper-catalyzed intermolecular cascade reactions between O-propargylic oximes and dipolarophiles.

Nakamura, L, Kudo, Y, Terada, M. (2013). Oxazepine synthesis by copper-catalyzed intermolecular cascade reactions between O-propargylic oximes and dipolarophUes. Ange-wandte Chemie International Edition, 52, 7536-7539. 

In the second synthesis,20 l-(2-acyloxyphenyl)-2-azidoethanones 3 cyclize to 1,3-benz-oxazepin-5-ols 4 in the presence of triethyl phosphite. As in the previous reaction, the intermediate phosphorus compounds are not isolated. 

Heating phenacyl 2-aminobenzoate with phosphoryl chloride yields 2-phenyl-4,1-benz-oxazepin-5(17/)-one (1. R = H). The method has been applied to the synthesis of a number of analogs.423... 

Treatment of the 1,2-oxazines 52 with carbon monoxide at 1000 psi in the presence of cobalt carbonyl brings about insertion of carbon monoxide to form the 1,3-oxazepines S3 <96TL2713>. A convenient route to P-lactams fused to oxepines is made available by alkene metathesis. Thus reaction of 4-acetoxyazetidin-2-one with ally alcohol in the presence of zinc acetate, followed by iV-allylation of the nitrogen affords the derivative 54 which cyclises by RCM to form the oxazepinone 55 <96CC2231>. The same communication describes a similar synthesis of 1,3-dioxepines. 

Other quinoline A-oxide derivatives have been examined. A 1,3-oxazepine is the major product of irradiation of 2-cyanoquinoline A-oxide whereas lactam formation predominates on irradiation of 4-methylquinoline N-oxide in aqueous ethanol.60 Lactam formation has been shown to be influenced by an external magnetic field and on this basis it has been proposed that the first step in this transformation is the formation of an excited radical-ion pair.61 1,3-Oxazepines undergo further reaction on prolonged irradiation. The synthesis of 4-substituted indoles, for example, has been accomplished in this way by irradiation of 5-substituted quinoline A-oxides.62... 

The Pd-based methodology described by Ma et al. has scope for the synthesis of fused 1,3-oxazepines <06T9002>. Considerable value would be added to this methodology if it could be adapted to the simpler 1,3-benzazepine system, perhaps via alternative methods for carbinolamine precursor generation. 

In a further example of a multicomponent synthesis, dihydrobenz[/] 1,4 oxazepin-5-ones were prepared in good yields in two steps by combining an initial three-component Ugi condensation with a subsequent Mitsunobu cyclisation to give (124 e.g. R1 = H, R2 = i-Pr, R3 = cyclohexyl, 65%) <06OBC4236>. 

Racker et al. have developed an interesting new combinatorial method for the synthesis of [l,4]oxazepin-7-ones (eg 139, R = Ph) from aldehydes and a-amino alcohols with the Baylis-Hillman reaction being a key step . 

Amongst other fused seven-membered ring systems, the synthesis of novel [l,2,5]selena (and [l,2,5]thia)diazolo[3,4-e][l,4]oxazepines from fused pyrimidine precursors has been described by Ueda and co-workers <00JHC1269>. 

Oxazepine chemistry includes some interesting rearrangement reactions both in synthesis and reactivity, many of which have parallels in the chemistry of the analogous diazepine systems. The preparative routes are classified as discussed earlier (p. 595). 

The Meisenheimer rearrangement of tertiary amine N- oxides has been applied to the synthesis of both monocyclic 1,2-oxazepines, e.g. (309) (65JOC3135, 65JCS1653, 82H(19)173), and those fused to benzene (80AJC833) and a variety of heterocyclic rings (80AJC1335). 

As with 1,4-oxazepines the Schmidt reaction of cyclic ketones and the Beckmann rearrangement of their oximes can be applied to the synthesis of monocyclic 1,4-thiazepines, 1,4- and 1,5-benzothiazepines and their 1-oxides and 1,1-dioxides (75CJC276). 

Pyridine is easily converted into 2-azabicyclo[2,2,0]hex-5-enes (358), which can be further transformed into useful 3-aza-7-oxatricyclo[4,l,0,02 5]hept-3-enes (359). Irradiation of (359) in acetonitrile gives the corresponding novel 1,4-oxazepines (360) in 90-95% yield (Scheme 49). This type of valence isomerization has been applied to the synthesis of fully aromatized 1,4-epines with two heteroatoms, such as 1,4-oxazepines, 1,4-thiazepines, 1,4-diazepines, and azepines (85CPB4572, 86CC1188, 87H(26)3085, 87JOC5247, 90CPB2911, 90TL20>. 

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