Preparation of 2,4-disubstituted cyclopentenones by enantioselective iridium-catalyzed allylic alkylation: synthesis of 2'-methylcarbovir and TEI-9826

A broadly applicable synthesis of chiral 2- or 2,4-substituted cyclopent-2-enones has been developed by combining asymmetric iridium-catalyzed allylic alkylation reactions and ruthenium-catalyzed ring-closing metathesis. Enantiomeric excesses (ee values) in the range of 95-99 % ee have been achieved. This method offers a straightforward access to biologically active prostaglandins of the PGA type. As an example, an enantioselective synthesis of the prostaglandin-analogue 13,14-dihydro-15-deoxy-Delta(7)-prostaglandin-A1-methyl ester (TEI-9826) has been carried out. Furthermore, the carbonucleoside 2'-methylcarbovir has been prepared from O-protected 4-hydroxymethyl-2-methyl-cyclopent-2-enone by Pd-catalyzed allylic amination.