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.

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

References

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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

<A NAME="RA33703ST-50">50</A>

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.

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