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.
Hibbs
David E.
DE
Department of Chemistry, University of Wales, Bangor, Gwynedd, LL57 2UW, UK, Peboc Division of Eastman Chemical (UK) Ltd., Industrial Estate, Llangefni, Anglesey, Gwynedd, LL77 7YQ, UK, and Department of Chemistry, University of Wales, Cardiff, P.O. Box 912, Park Place, Cardiff CF1 3TB, UK.
Hursthouse
Michael B.
MB
Jones
Iwan G.
IG
Jones
Wyn
W
Malik
K. M. Abdul
KM
North
Michael
M