Simple Syntheses of Seven-Membered Rings via an Entropy/Strain Reduction Strategy

Abstract

The straightforward four-step synthesis of unsaturated seven-membered carbocycles and heterocycles via a route starting from catechols and quinones is described. The route is based on the Perkin ring-closure reaction and was designed to alleviate the usual problems associated with the formation of medium rings. This is achieved through the presence of unsaturation in the starting mater­ial, which alleviates ring strain problems, reduces the entropy of ­activation and ensures that the chain ends are suitably orientated to encourage ring closure.

Key words

ring closure - carbocycles - heterocycles - seven-membered rings - catechol

References

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30

We use the cis,cis terminology to mean the general stereochemistry that places the carboalkoxy group and other alkene moiety on the same side of the double bonds. Individual compounds are of course named according to the E/Z nomenclature.

44

Throughout the work 3,5-di-tert-butylcatechol is widely used as the substrate of choice. It is a cheap readily available compound and the corresponding quinone is exceptionally stable in comparison with other quinones and as a result less polymeric material is observed. However as a result of the capricious nature of this substrate the results reported for 3,5-di-tert-butylcatechol are potentially not general to all substrates.

49

The current Aldrich catalogue (2003-2004) has the high grade LTA 17 times more expensive than the technical grade. High grade LTA is currently priced at £ 94.10 for 25 g. The same quantity of technical grade LTA costs just £ 5.50

50

Typical procedure: Catechol (1 equiv) was added slowly to a stirred solution of technical grade (95%) LTA (22 equiv) in toluene-MeOH (8 mL/g substrate). The mixture became deep red in colour initially and then darkened as the addition proceeded to finally yield a deep red solution. After stirring overnight a pale yellow solution resulted. The reaction mixture was evaporated and the red/yellow solid residue was treated with Et₂O. The resultant white precipitate was filtered and to the filtrate ethylene glycol (5 mL) was added. This prevented a black scum forming from the reaction of the residual lead salts during work up. The filtrate was washed with water, NaHCO₃ and water once more then dried over anhyd Na₂SO₄ The solvent was evaporated and the crude product purified via column chromatography on silica.