Bicyclic ethers, formation

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. 

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. 

A pentacyclic diterpene 1 called dictyoxetane contains a most unusual subunit, a 2,7-dioxatricyclo[4.2.1.03>8 ]nonane. During model studies designed to provide access to this key subunit the bicyclic ether 2 was synthesised in the hope that Sn displacement would generate the unsaturated tricyclic oxetane. There was no reaction when 2 was treated with base. Reaction with a catalytic amount of p-toluenesulfonic acid in DMF at 75°C for 24 hours resulted only in formation of 4-methylacetophenone. The hydroxy mesylate 2 is also reported to decompose to 4-methylacetophenone on storage. 

Lead tetra-acetate oxidation of the allylic alcohols (170)—(172) and (182) leads to the formation of the epoxides (183)—(186), products of a novel internal addition reaction of the electron-deficient alcohol oxygen to the allylic double bond. In some cases, (171) and (172), the formation of a new type of acetoxylated enol ether (173) and (174) is observed. Oxidation of the allylic dienols (175) and (176) gives the epoxyacetates (187) and (188). A variety of cyclization products was also isolated. Their formation requires an isomerization of the allylic trans double bond to cis.69 Lead tetra-acetate oxidation of dihydro-y-ionol (189) gives the new bicyclic ether... 

Whereas the glucose ester 9 has been identified for the first time as a natural wine constituent, glycoconjugates of its reduced form, i.e. of the monoterpene diol 11, are known Riesling wine constituents (2). Under acidic conditions, diol 11 was partially converted into the bicyclic ether 12, the so-called dillether (2). In analogy to the formation of ether 12 from terpene diol 11, a likely formation of lactone 10 from acid 9A could be be expected (cf. Fig. 5). This so-called wine-lactone 10, first identified as an essential oil metabolite in the Koala (55), has recently been established by Guth (34) as a major aroma contributor in two white wine varieties. The 35,3a5,7aR-configured isomer of 10, which has been identified in wine, is reported to possess an unusual low flavor threshold of 0.01-0.04 pg/L of air and a sweet, coconut-like aroma (55). 

Zimmerman and Hofacker have studied the photochemically induced SET reactivity of the 1,4-dienes (74). The sensitizers used were dicyanoanthracene and dicyanonaphthalene. The radical cations of the 1,4-dienes undergo regioselective cyclization to the cyclic radical cations (75) which ultimately afford the final products (76). The SET-induced photochemistry of other non-conjugated dienes such as geraniol (77) has been studied. The results demonstrate that with DCA as the sensitizer in methylene chloride a contact radical-ion pair is involved and this yields the cyclopentane derivatives (78) and (79) in the yields shown. The cyclization is the result of a five-centre cyclization. With the more powerful oxidant dicyanobenzene as the sensitizer and in acetonitrile as solvent, separated radical-ion pairs are involved and this leads to the formation of the bicyclic ethers (80) and (81). DCA-sensitized reactions of the dienes (82) and E,E-(S3) and the bicyclohexane (84) have been studied. At low conversion the irradiation of (84) under these conditions affords a mixture of the dienes (82) and , -(83) in ratios that are independent of temperature. 

There are many examples of such reactivity and some of these have been reviewed by Roth and coworkers, a research group that is extremely active in this area. An example that is typical of the processes encountered involves the cyclization of the diene geraniol (1). In this case the sensitizer is 9,10-dicyanoanthracene (DCA) and the reactions are carried out in methylene chloride. The authors state that a contact radical-ion parr is involved, i.e. the radical cation of the diene is in close proximity to the radical anion of the DCA. Reaction within this yields the cyclopentane derivatives 2 and 3 in the yields shown. The ring formation is the result of a five centre CC cyclization within the radical cation of 1. When a more powerful oxidant such as p-dicyanobenzene is used as the sensitizer in acetonitrile as solvent, separated radical-ion pairs are involved. This leads to intramolecular trapping and the formation of the bicyclic ethers 4 and 5 . The bicyclic ether incorporates an aryl group by reaction of the radical cation of the diene with the radical anion of the sensitizer (DCB). This type of reactivity is referred to later. Other naturally occurring compounds such as (/fj-f-bj-a-terpineol (6) and (R)-(- -)-limonene (7)... 

Similarly, ion 68 is generated via transannular alkoxy transfer to the silicenium ion of 6966. It has not been definitively proven whether 70 is an intermediate or a transition state en route to 68. The study of the cis/trans isomeric pairs of 69 clearly suggests that the formation of 68 is much more enhanced for the cis isomer. When starting from trans-69, some ring-opening processes must be involved. The nature of the neutral formed in the reaction 70 - 68 has yet to be elucidated. It is suggested66 that starting from ds-69 the bicyclic ether 71 is formed (reaction 39). 

It is believed that the process involving the formation of intermediate A and its intramolecular cyclization with producing radical B is responsible for the formation of bicyclic ethers 7 and 9 (Fig. 9.2). Similar mechanism was suggested to explain the formation of bicyclic and spiro-ethers 10-13, obtained from the corresponding esters containing five- and six-membered alicyclic fragment. ... 

A majority of the remaining solvolytic studies involve base catalysis, and 0 is probably the reactive oxygen species present. 0 -5 participation was suggested to account for the formation of the bicyclic ether (192) from the alkaline hydrolysis of trans-4-chlorocyclohexanol. The rate of reaction is 1100 times less than that of 4-chloro-l-butanol under the same conditions, but, as discussed above, O attack was not suggested in the hydrolysis of the latter. 

In the same [3.2.1] bicyclic ether system with methyl substitution a to the carbonyl, (1) adds to the double bond without cyclobutanol formation (eq 12). With the monomethylated ketone (11) an 8 1 mixture of regioisomers is produced, with (12) predominating. 

Various bicyclic and polycyclic compounds are produced by intramolecular reactions] 127]. In the syntheses of the decalin systems 157 [38] and 158 [128], cis ring Junctions are selectively generated. In the formation of 158, allyhc silyl ether remains intact. A bridged bicyclo[3.3. l]nonane ring 159 was constructed... 

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