Stereocontrol in organic synthesis using silicon-containing compounds. A synthesis of a (±)-carbacyclin analogue with the geometry of the exocyclic double bond controlled by the protodesilylation of an allylsilane

Abstract

The known ketone, 7-tert-butyldimethylsilyloxybicyclo[3.3.0]oct-8-en-2-one 11, was converted in five steps into 3-(4′-methoxycarbonylbutylidene)-7-tert-butyldimethylsilyloxy-8-cyanobicyclo[3.3.0]octan-2-one 13. Reduction gave the diastereoisomeric pair of allylic alcohols 14 and 15, both of which were converted into the allylsilane, 3-(1′-dimethylphenylsilyl-4′-methoxycarbonyl)butyl-7-tert-butyldimethylsilyloxy-8-cyanobicyclo[3.3.0]oct-2-ene 20. Protodesilylation of the allylsilane gave a high level of selectivity (>96∶4) in favour of the carbacyclin analogue, 5-(4′-methoxycarbonyl)butylidene-3-tert-butyldimethylsilyloxy-2-cyanobicyclo[3.3.0]octane 22, having the exocyclic double bond with the E-configuration.