Premium
Preparation of 2,4‐Disubstituted Cyclopentenones by Enantioselective Iridium‐Catalyzed Allylic Alkylation: Synthesis of 2′‐Methylcarbovir and TEI‐9826
Author(s) -
Dübon Pierre,
Schelwies Mathias,
Helmchen Günter
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200800495
Subject(s) - enantioselective synthesis , tsuji–trost reaction , allylic rearrangement , chemistry , amination , iridium , enantiomer , ruthenium , alkylation , catalysis , enone , stereochemistry , combinatorial chemistry , medicinal chemistry , organic chemistry
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‐Δ 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.