2.7- Dihydro-3,4-benzoxepines

A further development of this route (71JOC4028), involving the cyclization of 3-(o-formylphenoxy)propyltriphenylphosphonium salts in methanol, has led to high yields of 2-methylchromene. In the detailed mechanism which has been proposed, an o-quinoneallide is considered to arise by the ring opening of an initially formed benzoxepin derivative. Indeed, 2,3-dihydro-1-benzoxepin is the major product of the reaction in aprotic solvents. 

Benzoxepin-4-carbaldehyde, dihydro-from chromones, 3, 713 Benzoxepin-4(3H)-one from isochromanone, 3, 726 [l]Benzoxepino[3,4-d]selenazoles synthesis, 6, 345 Benzoxepins... 

When the analogous starting material without the hydroxy group was used, 2,3-dihydro-l-benzoxepin was obtained in low yield (8%). The main product (87%) was 2-methyl-2//-chromene.97... 

Direct irradiation of substituted 1,4-dihydro-1,4-epoxy naphthalenes gives small quantities of 3-benzoxepins 16 amongst other products.144 146,256 The primary product of this reaction is probably a 3-oxaquadricyclane derivative which can react to give the benzoxepin under thermal conditions. The formation of benzoylindene compounds as the main products from the photochemical rearrangement of l,4-diphenyl-l,4-dihydro-l,4-epoxynaphthalenes has been shown to proceed via the corresponding 3-benzoxepins.146 The irradiation of naphthalene 1,4-oxides in the presence of a photosensitizer did not lead to benzoxepin derivatives.144... 

The dehydrohalogenation reaction has been extended to benzannulated oxepins. Elimination of hydrogen bromide from 3-bromo-4-phenyl-2,3-dihydro-l-benzoxepin with 1,5-diazabicyclo-[4.3.0]non-5-ene gives 4-phenyl-1-benzoxepins 15a15 and 15b16 in low yield. 

Dichloro- and l,2-dibromo-l,2-dihydro-3-benzoxepins are dehalogenated with zinc in methanol to give 3-benzoxepin (6a) in excellent yield.93 A methoxycarbonyl group in the 2-position, however, diminishes the yield of 6b considerably.91... 

Irradiation of anft -9,10-epoxy-1.4-dipropyl-l,4-dihydro-l,4-ethanonaphthalene-2,3-dione results in a stepwise loss of two carbonyl groups and the formation of l,5-dipropyl-3-benzoxepin as the major product (25%).171... 

The oxidation of 1,4-dihydronaphthalene with oxygen with irradiation gave l,2-dihydro-2-naphthyl hydroperoxide that decomposed thermally to 3-benzoxepin (3).189... 

This reaction can also be used for the synthesis of substituted 1-benzoxepins with one modification instead of the 4/T-benzopyran the 2/7-isomer must be used. 2-[Diazo(phosphoryl)meth-yl]-2//-benzopyrans decompose in the presence of ))3-allylpalladium chloride dimer with elimination of nitrogen to give 1-benzoxepins 2.192 In some cases, the reaction takes a different course and gives 2-methylene-2//-benzopyrans 3.192 In this respect, the bicyclic system behaves differently to the monocyclic diazo(pyranyl)methane. The 2-isomers of the latter structure could not be isolated and gave l//-l,2-diazepines.190 The 4//-benzopyrans do not form benzoxepins but undergo an intramolecular [2+1] cycloaddition to 3,4-dihydro-2,3,4-metheno-2//-ben-... 

When dimethyl 3-benzoxepin-2,4-dicarboxylate is reacted under controlled conditions (15 min) with hydrogen it is possible to isolate dimethyl l,2-dihydro-3-benzoxepin-2,4-dicarboxylate.17 Hydrogenation of 2-nitrodibenz[, /]oxepin-10-carboxylic acid in the presence of palladium on potassium carbonate results in the reduction of the nonaromatic C C double bond and the nitro group to give 2-amino-10,l l-dihydrodibenz[i,/]oxepin-10-carboxylic acid.107... 

Benzoxepin undergoes addition of bromine and chlorine to give l,2-dibromo-l,2-dihydro-3-benzoxepin (2 a) and 1,2-dichloro-l, 2-dihydro-3-benzoxepin (2b), respectively.93 The bromination reaction of dimethyl 3-benzoxepin-2,4-dicarboxylate takes the same course to give 2c.91... 

Z)-Styryloxiranes 154 undergo a thermal ring expansion reaction to give carbonyl ylides 155, which cyclize to 2,7-dihydro-3,4-benzoxepines 156 (Scheme 47) (79TL4049 85CB4035). 

The synthesis of selectively substituted benzoxepines from ortho-substituted aryl iodides and bromoenoates has been achieved by Lautens and coworkers by palladacycle alkylation followed by an intramolecular Heck reaction under the modified conditions reported in Eq. (8) for synthesis of l-(l-ethoxycarbonylmethy-lene)-9-methyl-4,5-dihydro-3-benzoxepine [8]. In the second example (Eq. 9) the palladium-bonded biphenylyl inserts diphenylacetylene to form 1,5-di-i-propyl-9,10-diphenylphenanthrene[9]. In the last case the synthesis of 4-methyl-5H-phenanthridin-6-one is achieved by palladium-catalyzed sequential C-C and C-N bond formation starting from o-iodotoluene and o-bromobenzamide [10]. 

Similarly, Lautens and coworkers could readily expand this concept to the synthesis of 2-substituted-4-benzoxepines and 2,5-disubstituted-4-benzoxepines [75], and in an intermolecular-intramolecular bisalkylation-alkenylation sequence to the syntheses of oxacycles such 2,3-dihydro-... 

Benzoxepin 5-Chlor-4-formyl-2,3-dihydro- E3, 172 (Keton + C12CH-CH2-C1)... 

Z)-Styryloxiranes give 2,7-dihydro-3,4-benzoxepines with phenyl ring participation by cycloaddition via an extended dipole (Eq. 389). ... 

A new heterocyclic ring system, 5/-/,12/-/-[1]Benzoxepino[4,3-b]indol-6-one, was prepared by the Fischer indole cyciization of a substituted benzoxepin-5b-one phenylhydrazone by G. Primofiore and co-workers. The phenylhydrazone precursor was prepared via the Japp-Klingemann reaction of the corresponding 3,4-dihydro-4-hydroxymethylene[1]benzoxepin-5(2H)-one. 

The reagent reacts with the sodium salt of salicylaldehyde (6) to give 2,3-dihydro-7-benzoxepine (7) and 2-methyl-3-chromene (8). 

Octahydro-80-hydroxy-2,2,5aa,9a-tetramethyl-3a,9aa-methano-l-benzoxepin-5(5a//)-one 4/l,15-Dihydro-3p-Hydroxy-9-oxoagarofuran (Table 9. Entry 8) Typical Procedure... 

Expansion of the pyrone ring of chromanones has been achieved by reaction with ethyl diazoacetate and BuLi at —78°C [to produce the a-diazo-ester (154)] followed by acid-catalysed conversion, at room temperature, into the benzoxepin (155). De-ethoxycarbonylation led to the parent 2,3-dihydro-l-benzoxepin-4-(5jF/)-one (156). By a similar sequence, isochroman-4-one (157) was converted into the hitherto unknown l,5-dihydro-2-benzoxepin-4(3H)-one (158). ... 

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