Benzodioxepines, synthesis

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>. 

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... 

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. 

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>. 

This collection begins with a series of three procedures illustrating important new methods for preparation of enantiomerically pure substances via asymmetric catalysis. The preparation of 3-[(1S)-1,2-DIHYDROXYETHYL]-1,5-DIHYDRO-3H-2.4-BENZODIOXEPINE describes, in detail, the use of dihydroquinidine 9-0-(9 -phenanthryl) ether as a chiral ligand in the asymmetric dihydroxylation reaction which is broadly applicable for the preparation of chiral dlols from monosubstituted olefins. The product, an acetal of (S)-glyceralcfehyde, is itself a potentially valuable synthetic intermediate. The assembly of a chiral rhodium catalyst from methyl 2-pyrrolidone 5(R)-carboxylate and its use in the intramolecular asymmetric cyclopropanation of an allyl diazoacetate is illustrated in the preparation of (1R.5S)-()-6,6-DIMETHYL-3-OXABICYCLO[3.1. OJHEXAN-2-ONE. Another important general method for asymmetric synthesis involves the desymmetrization of bifunctional meso compounds as is described for the enantioselective enzymatic hydrolysis of cis-3,5-diacetoxycyclopentene to (1R,4S)-(+)-4-HYDROXY-2-CYCLOPENTENYL ACETATE. This intermediate is especially valuable as a precursor of both antipodes (4R) (+)- and (4S)-(-)-tert-BUTYLDIMETHYLSILOXY-2-CYCLOPENTEN-1-ONE, important intermediates in the synthesis of enantiomerically pure prostanoid derivatives and other classes of natural substances, whose preparation is detailed in accompanying procedures. 

Natural products with a ew-dimethyl benzodioxepin ring have been detected, for example, the antifungal natural product strobilurin (31) <90JAN661>, and several benzodioxepin derivatives, i.e., compounds (32) and (33), with a similar structural feature have been synthesized in the total synthesis of (-I-)-paraherquamide B <90TL6325, 96JA557>. 

The ew-dimethyl 2,3-dihydro-5/f-l,4-benzodioxepin moiety occurs in several natmal products, for example, in the paraherquamides, which exhibit potent anthelmintic and antinematodal activity, and in the marcfortines (72 marcfortine B). In the course of the total synthesis of (+)-para-herquamide B (71), the synthesis of the benzodioxepin unit by phenylselenoetherification and by epoxidation followed by a Lewis add-mediated ring closure was explored, but the phenylselenoetherification only gave poor yields of (74). The dehydration of the secondary alcohol (77) was effected with methyltriphenoxyphosphonitun iodide (MTPI) in HMPA (Scheme 7) <90TL6325, 96JA557). 

Analogous to the synthesis of l,4-benzodioxepin-5-ones, the benzoxathiepinones (166) were prepared by the reaction of ethyl 2-thiobenzoates with chlorohydrin and glycerol chlorohydrin and cyclization of intermediate (165) (Scheme 17) <75BSF277>. The sodium borohydride reduction of bienzoxathiepinone (167) has also been studied <82NJC149>. 

Flavanones undergo a Baeyer-Villiger rearrangement to dihydro-l,5-benzodioxepin-2-ones on treatment with H2O2 and methyltrioxorhenium <01TL5401>. The synthesis of benzoxazepines from chromanones forms part of a review of the 7-membered ring compounds <01JHC1011>. 

Nunez MC, Pavani MG, Diaz-Gaviltm M, Rodriquez-Serrano F, Gomez-Vidal JA, Marchal JA, Aranefa A, GaUo MA, Espinosa A, Campos JM (2006) Synthesis and anticancer activity studies of novel l-(2,3-dihydro-5ff-l,4-benzodioxepin-3-yl)uracil and (6 -substituted)-7-or 9-(2,3-dihydro-5i7-l,4-benzodioxepin-3-yl)-7//- or 9//-purines. Tetrahedron 62 ... 

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