Bicyclic ethers

Yokoyama, Y. and Hall, H. K. Ring-Opening Polymerization of Atom-Bridged and Bond-Bridged Bicyclic Ethers, Acetals and Orthoesters. Vol. 42, pp. 107—138. 

The difference in behavior of the cis- and trans-isomers 43 and 45 is ascribed mainly to the greater ring strain in the trans-isomer which results in a more favorable free energy change for its polymerization. This result is similar to that reported for the polymerization of cis- and frans-8-oxabicyclo[4.3. OJnonane 48 and 4936. The molecular weights of the polymers of the bicyclic ether 49 were, however, much higher than those of the polymers of the bicyclic acetal 45. 

Bicyclic ether Four-membered rlng(22) W423... 

Vinylfurans can be formed from 2,3-epoxy-6-octenols via a C-O coupling reaction leading sometimes also to bicyclic ethers as by-product 1[67]... 

The isolation of benzvalene (61) from the irradiation of benzene at 254 nm and the observation that this compound produces the expected bicyclic ethers when treated with acidified methanol lend credence to the intermediacy of (61).(90> Photolysis of benzene in acetic acid was found to result in formation of acetates (64)—(67), with the product composition changing with time ... 

It is believed that the regiospecifidty of the dioxabicyclization and the concurrent formation of bicyclic ethers 48 and 49 both result from equilibrium control of reversible (per)oxymercuration — de(per)oxymercuration. Thus to optimise the yield of 47 it is important to minimize the amount of water present in the reaction mixture and use of concentrated hydrogen peroxide (>80%) with anhydrous mercury(II) trifluoroacetate is recommended. 

For example, the parent bicyclo[2.2.1] system 9 affords the epoxy-aldehyde 64 in high yield (97 %) in nonpolar solvents (cyclohexane)62). The mechanism is rationalized in equation 52. Small amounts (ca. 1 %) of the bicyclic ether 65 are also formed, but it is known that 64 rearranges into 65 on heating 62). 

Scheme 5.6. Synthesis of fused oxetanes 5-28 and bicyclic ethers 5-29.

Let us now discuss heterocyclic propellanes and dispirans. 8,1 l-Dioxa[4.3.3]propell-3-ene 34 was prepared (in 73% yield) by heating the tetrol 33 with KHS04 at 190-200 °C4e). This was accompanied by the bicyclic ether 35 (10% yield) but no... 

The intramolecular Heck cyclization of 4-iodopyridine 175 with a pendant crotyl ether led to a mixture of bicyclic ethers 176 and 177 in which the endocyclic isomer 176 was predominant [138],... 

Tributyl tin radical mediated cyclization of the glucose derived exo-methylene furanose derivatives led to highly functionalized cA-fused bicyclic ethers. The product could subsequently be transformed into optically active tricyclic nucleoside analogue or oxepine derivative (Fig. 51).67... 

Fig. 51 Radical approach towards highly functionalised fused bicyclic ethers.

The reaction of hexamine dinitrate (241) with 98% nitric acid at —30°C, followed by quenching with aqueous sodium nitrate, yields the nitrosamine (244). When the same reaction is cautiously quenched with ethanol the ethoxyether (245) is obtained. Treatment of the ethoxyether (245) with cold absolute nitric acid yields the bicyclic ether (246). ° Treatment of any of the cyclic nitramines (242)-(246) with nitric acid and ammonium nitrate in acetic anhydride yields RDX. ° Hexamine dinitrate is often used in low temperature nitrolysis experiments in order to avoid the initial exotherm observed on addition of hexamine to nitric acid. 

The bicyclic ethers 277 and 278 are obtained by a transannular oxidative cyclization using HTIB. Although this reaction shows poor regioselectivity, the addition to the double bond proceeds with high trans stereoselectivity (87TL5229) (Scheme 70). 

More structurally complex epoxides can be ring-opened intramolecularly in a synthetically useful fashion. Thus, in their approach to methyl-substituted trmis-fused tetrahydropyran subunits found in marine natural products, Mori and co-workers <99TL8019> treated the polyfunctional arylsulfonyl epoxide 67 with Lewis acid to induce a (s-endo cyclization onto the epoxide moiety, with concomitant ejection of arylsulfinate, to provide the bicyclic ether 68. This system was found to be highly sensitive to the nature of the Lewis acid catalyst used. 

Plumet et al. described domino metathesis of propargyl (2-endo-7-oxanorborn-5-enyl) ethers 62a-62c with allyl acetate in the presence of Grubbs ruthenium catalyst Ic (Scheme 22). The reaction proceeds stereoselectively to produce substituted m-fused bicyclic ethers 63a-63c. In a similar manner, indolizidinone derivative 64 is obtained from compound 62d instead of pyrrolizidine derivative 63d. ... 

Novel preparative possibilities arise when cyclopropylidene intermediates are generated from functionalized dihalocyclopropanes. Thus Baird has shown that bicyclic ethers may be formed in high yield by an intramolecular insertion from cyclopropyl alkyl ethers [120],... 

Brominative cycHzadon of polyenes. Treatment of ncrolidol (2) with 1 results in formation (in low yield) of a- and /5-synderol (3 and 4) and the bicyclic ethers 3/3-bromo-8-epicaparrapi oxide (5) and the C -cpimcr. 

Presumably, compound 115 has also been isolated, as an extremely volatile liquid, in 15% yield from a complex mixture of other bicyclic ethers by oxidation of 1,6-hexanediol (118) with lead tetraacetate198,199 (see Scheme... 

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