Synthesis of enantio- and diastereomerically pure, tetra- and penta-substituted cyclopentanes by the desymmetrization of endo-norborn-5-ene-2,3-dicarboxylic anhydrides

The desymmetrization of endo-norborn-5-ene-2,3-dicarboxylic anhydrides by methyl (S)-prolinate followed by ozonolysis of the resulting carboxylic acids is used to prepare enantio- and diastereomerically pure, tetra- and penta-substituted cyclopentane derivatives in which all of the substituents on the cyclopentane ring are syn to one another. The initial products of this chemistry (2a,b and 18a,b) contain two aldehyde groups, one of which exists as a hemiacetal. This allows subsequent chemistry to be carried out regioselectively at one of the two aldehyde groups. Hence, the sodium borohydride reduction of hemiacetals 2a,b can be controlled to give either a bicyclo[3.2.1] (4) or bicyclo[3.3.0] lactone (5) as the product. The addition of allylindium to hemiacetals 2a,b occurs both regio- and diastereoselectively to give polycyclic acetal 12, the stereochemistry of which is consistent with a chelation controlled addition. It is possible to remove the proline ester based auxiliary from the cyclopentane derivatives by gamma-lactone formation under mild reaction conditions.