Dioxepins, synthesis

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. 

Bismuth(III) Triflate-Catalyzed Synthesis of Dioxolanes, Dioxanes, and Dioxepines... 

This methodology was also applicable to the synthesis of dioxepines from aldehydes and cA-2-butene-l, 4-diol (Table 6). 

Podgorski DM, Krabbe SW, Le L, Sierszulski PS, Mohan RS (2010) Bismuth compounds in organic synthesis. Synthesis of dioxanes, dioxepines and dioxolanes catalyzed by bismuth (III) triflate. Synthesis 2771-2775... 

Synthesis of 1,2-dioxepane derivatives can be achieved through mainly four methods, three of which have the potential 0-0 bond already in one reactant, namely ozone, oxygen gas, or a hydroperoxide moiety. The fourth method involves the linking of two oxygen atoms to form a 1,2-dioxepine bond. 

Dihydroxy-l,3-dioxepins readily undergo vinylacetal rearrangement in the presence of a Lewis acid to give tetrahydrofuran-3-carbaldehydes (CHEC-II(1996)). This methodology was applied in a tandem Heck reaction -rearrangement process for the synthesis of a variety of 2,4-substituted tetrahydrofuran-3-carbaldehydes (Scheme 19) <2006CC3119>. 

In the synthesis of the monocyclic bisabolene-type sesquiterpenoids (-f)-curcuquinone and (—)-curcuhydro-quinone, 1,3-diol 107 was obtained by ozonolysis of 4,5-dihydro-l,3-dioxepin 106 (obtained by Heck reaction, see Section 13.11.10) and reductive workup (Scheme 25) <2003ARK232>. 

For the synthesis of several other biaryl-derived dioxepins for second-order nonlinear optics, see <1996JA6841>. 

Only a few reports have dealt with this type of synthesis of the 1,3-dioxepin and 1,3-dithiepin moiety. Dithiepane 148 could be obtained by an intramolecular transacetalization of mercaptane 147 (Scheme 40) <2000T10101>. 

Synthesis of acetonides can also be performed using 2-methoxypropene instead of 2,2-dimethoxypropane <20050L5011> however, 4,5-dihydro-l,3-dioxepins, such as 216 (Scheme 61), can only be obtained by direct acetalization or transacetalization with special substrates. 

Another useful procedure for the synthesis of dioxepins, oxathiepins, as well as dithiepins under basic conditions involves deprotonation of a diol or dithiol precursor and treatment of the resulting anion with a gdihalo compound, as demonstrated with the synthesis of the TADDOL-derived oxathiepin 64 <1991SL844> and biaryl derivative 132 <2005TL7291> (Scheme 62) ... 

The Heck reaction of 4,7-dihydro-l,3-dioxepins has found further applications in the total synthesis of naturally occurring compounds. For example, 4,5-dihydro-l,3-dioxepin 241 was prepared as an intermediate in the synthesis of Brefeldin A <1999JOC3800>, and the /fV/-butyl derivative of 106 in the synthesis of (-l-)-curcuquinone and (—)-curcuhydroquinone (Scheme 72) <2003ARK232>. 

However, it has turned out that there are a few synthetic methods having broad scope, that is, (a) for the synthesis of dioxepins and dithiepins (i) transacetalization of the corresponding diol or dithiol, respectively, with an open chain acetal (ii) treatment of the corresponding diol or dithiol with sodium borohydride and reaction of the resulting dianion with a gem-dihalogen derivative. The latter method is particularly useful for the synthesis of dioxepins and dithiepins unsubstituted in the 2-position (b) for the synthesis of 4,5-dihydro-l,3-dioxepins (i) metal- or base-catalyzed double-bond isomerization and (ii) Heck vinylation or arylation, respectively, for the synthesis of 6-substituted 4,5-dihydro-l,3-dioxepins. 

Dihydro-l,3-dioxepins were used as chiral building blocks <2001AG(E)177> and substrates for the synthesis of naturally occurring compounds <2003ARK232>. 

The reaction of trifluoroacetylnaphthylamine 25 with diols and dithiols offers a convenient high yield synthesis of 1,4-dioxepins and dithiepins (Equation 14) <1998H(49)297>. 

A serendipitous synthesis of the l,4-dioxepin-5-one derivative 228 has been reported based on acid chloride formation from the acid 227, followed by a ring opening and ring closing sequence on exposure of the acid chloride to 48% HBr solution [01TL2305]. 

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