Benzodioxepination

H- 1,5-Benzodioxepin, 3,4-dihydro-synthesis, 7, 622 5H-l,4-Benzodioxepinediones synthesis, 7, 622 5H-l,4-Benzodioxepinones synthesis, 7, 622 lH-2,3-Benzodioxepins synthesis, 7, 620 3H-2,4-Benzodioxepins synthesis, 7, 621... 

In a report dealing with the synthesis and anticancer activity of (6 -substituted)-7- and 9-(2,3-dihydro-5i/-l,4-benzodioxepin-3-yl)purines, transformations of V9 -alkyl-6 -halopurines have been described <06T11724>. 

Two new strobilurins O, 113 and P, 114, containing benzodioxepin skeletons, were isolated from the mushroom Mycena galericulata and characterised spectroscopically <00JAN297>. 

A highly regio- and stereo-regulated synthesis of the (Z)-l,4-benzodioxepin-5-ones 115 (Ar = Ph, 4-MeOC6H4 X = 0) has been reported, and involved, at the penultimate stage, cyclization of disubstituted alkynes on treatment with copper (I) iodide. <00JCS(P1)775>. 

This intramolecular etherification approach has successfully been applied to the syntheses136 of siccanin137 and clusifoliol,136 and a formal synthesis of morphine.138 Examples of tandem inter- and intramolecular etherification reactions have also been reported which convert catechol and o-aminophenol derivatives into benzodioxins (Equation (24)),139-141 benzodioxepines,142 and morpholines.139,140... 

Quinghaosu (Artemisinine) Quinghaosu, octahydro-3,6,9-trimethyl-3,12-epoxy-127/-pyrano-(4,3-di)-l,2-benzodioxepin-10-(37/)-one (37.1.1.57), is isolated from the plant Artemisia annua [26]. 

A number of 5//-l,4-benzodioxepin-ones and -diones have been prepared (72HC(26)319, p. 339). The reaction of the sodium salt of salicylic acid with 2-chloroethanol gave (269) (75BSF(2)277) and treatment of the methyl ester of 2-acetyl-6-chloro-3,5-dimethoxyphenoxyacetic acid with 3M hydrochloric acid gave (270). The dione (271) was prepared by heating 2-carboxy-5,6-dimethoxyphenoxyacetic acid in acetic anhydride and (272) was prepared from chloroacetylsalicylic acid. 

The two major routes to 3,4-dihydro-2JT-l,5-benzodioxepins (274) from (273) and (275) are applicable to a wide range of substituted derivatives. The 3-oxo derivative, important as a perfume odorant, can be prepared via the reaction of 1,2-dihydroxybenzene with chloroacetonitrile (75CJC2279) or via a Dieckmann cyclization (74USP3799892). 

Dihydro-5//-1,4-benzodioxepin (408) and halogenated derivatives (407) and (409) are obtained from 1,4-benzodioxin (406) by dihalogencarbene addition, thermolysis, and reduction (83AG(E)64). 

Recent results by St-Jacques and collaborators (45) have revealed that the ring conformation in 2,4-benzodioxepin which can be the chair 39 (Fig. 8), the twist boat 40 or the boat form 1, was determined by the nature of substitution. A chair (39) with a minor amount of the twist-boat (40) was observed for the non substituted compound 42, whereas the chair form was found for the methyl derivative 43 and the twist boat-form for the dialkyl derivatives 44, 45, and 46. 

The reaction of a,/3-unsaturated benzodioxepin 116 with fert-butyllithium in THF at — 78 °C produced a lithium alkoxide, which was trapped in situ with 2,2,2-trifluoroacrylate to give acryloyl (lZ,3T)-dienyl ether 117 with high diastereoselectivity (Scheme 28) <20050BC1308>. The procedure has found application in the synthesis of carbo-sugars via Diels-Alder reaction. 

Nuclear magnetic resonance (NMR) spectroscopy, with X-ray analysis, forms the basis for the determination of the structures of most of the compounds discussed in this chapter. H and 13C NMR played a key role in the revision of the structure of the antifungal metabolite strobilurin D 2, which was shown to contain a benzodioxepin moiety rather than epoxide <1999T10101>. 9-Methoxystrobilurin K was also shown to contain a 1,4-benzodioxepin <1997TL7465>. 

Ring-closing metathesis (RCM) has been employed for the construction of 1,5-benzodioxepine derivatives (Equation 6) <2004TL2631>. 

A highly regio- and stereoselective synthesis of 3-arylidene-l,4-benzodioxepin-5-ones has been achieved with palladium-copper catalysis (Scheme 7) <2000J(P1)775>. 

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