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.
Dübon
Pierre
P
Organisch-Chemisches Institut der Universität Heidelberg, Im Neuenheimer Feld 270, Heidelberg, Germany.
Schelwies
Mathias
M
Helmchen
Günter
G
D000478:Alkylation; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D015224:Dideoxynucleosides / Q000138:chemical synthesis*; D007495:Iridium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011455:Prostaglandins A, Synthetic / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
C532172:2'-methylcarbovir; D015224:Dideoxynucleosides; D011455:Prostaglandins A, Synthetic; C469647:TEI9826; D007495:Iridium