Benzoxepin synthesis

Benzoxepin, 2,3,4,5-tetrahydro-applications, 7, 590 bond fission, 7, 549 synthesis, 7, 577... 

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... 

Another application of this method is the synthesis of 5,10-epoxy[10]annulene (7) from 2,3.6,7-tetrabromo-4a,8a-epoxydecahydronaphthalene.152-154 The byproduct is 1-benzoxepin (8). The 5,10-cpoxyannulcnc (7) incorporates the oxepin structure. The annulene can be converted to 1-benzoxepin by proton catalysis.153154... 

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-... 

Some thermal rearrangement reactions of 1-benzoxepins show the participation of the solvent in the formation of stable products, e.g. 6172,247 and 7.177 The synthesis of methoxy-substituted 1-benzoxepins by O-methylation of the anions generated by the deprotonation of the respective oxo derivative with ferf-butoxide is often limited by the rapid aromatization to methoxy-substituted naphthalenes, e.g. 816 and 9,173 under the reaction conditions.16,173... 

The synthesis of these rings involves annulation of the furan ring onto the preformed benzoxepine core or intramolecular oxepine C-C bond formation of the furan precursors. Thus, 2-methyldibenzo[ 7,/]furo[2,3-d]oxepines 148 (R = H, Cl)... 

Benzoxepins are frequently synthesized by cyclization of alkyl aryl or diaryl ether precursors. An intramolecular Wittig reaction (equation 48) is used to provide the ring closure step in the synthesis of 1-benzoxepin (28) (68JOC2591). An internuclear cyclization reaction of an aromatic sulfonyl chloride (equation 49) occurred upon heating (250 °C) in the presence of a copper chloride catalyst to yield tribenz[6,d,/]oxepin (175). The analogous thiepin (see equation 71) may also be synthesized by this route (65T1299). 

The synthesis of the benzoxepin (167) involves an intramolecular Wittig reaction (Scheme 19) (68JOC2591). 

The formation of a benzoxepin derivative during the synthesis of chromenes from phosphonium salts has been postulated (see p. 749). In keeping with this idea, chromenes are produced by ring opening of benzoxepin (121) with methoxide ion in DMF (69C108). The initial product, a butadienylphenol (122), undergoes a [l,7]-hydrogen shift to the quinoneallide. 

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-... 

Reductive cleavage. Selective scission of the oxymethylene bridge of 1 occurs on exposure to SMEAH in THE/ None of the alternate benzoxepin product (3) is formed, since only the jS-oxygen is disposed perpendicularly to the cyclo-hexadienone moiety. The product is an intermediate in a synthesis of vitamin E (4). 

Benzazepine and benzoxepine ring systems showed high CNS activity and their syntheses have been reported [142]. The key step in this synthesis exploited an alternative route to form oxepine or thiepine ring systems 61 via a Pd-catalyzed cyclo-amination of 60. Overall, the best yields were achieved with Pd2(dba)3 as the palladium source, P(Z-Bu)3 as the ligand, Z-BuONa alone or with K2CO3, in toluene [142]. 

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