Total syntheses of (S)-(-)-zearalenone and lasiodiplodin reveal superior metathesis activity of ruthenium carbene complexes with imidazol-2-ylidene ligands.
Total syntheses of the bioactive orsellinic acid derivatives zearalenone 3 and lasiodiplodin 1 are reported based on a ring-closing metathesis (RCM) reaction of styrene precursors as the key steps. These and closely related macrocyclizations are catalyzed with high efficiency by the "second generation" ruthenium carbene catalyst 5 bearing a N-heterocyclic carbene ligand, whereas the standard Grubbs carbene 4 fails to afford any cyclized product. Only the (E)-isomer of the macrocyclic cycloalkene is formed in all cases. The substrates for RCM can be obtained either via a Stille cross-coupling reaction of tributylvinylstannane or, even more efficiently, by Heck reactions of the aryl triflate precursors with pressurized ethene. Furthermore, the synthesis of 1 via RCM is compared with an alternative approach employing a low-valent titanium-induced McMurry coupling of dialdehyde 47 for the formation of the large ring. This direct comparison clearly ends in favor of metathesis which turned out to be superior in all preparatively relevant respects.
Fürstner
A
A
Max-Planck-Institut für Kohlenforschung, D-45470 Mülheim/Ruhr, Germany. fuerstner@mpi-muelheim.mpg.de
Thiel
O R
OR
Kindler
N
N
Bartkowska
B
B
D004968:Estrogens, Non-Steroidal / Q000138:chemical synthesis*; D006838:Hydrocarbons; D008024:Ligands; D008697:Methane / Q000031:analogs & derivatives* / Q000494:pharmacology; D012428:Ruthenium / Q000494:pharmacology*; D015025:Zearalenone / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
D004968:Estrogens, Non-Steroidal; D006838:Hydrocarbons; D008024:Ligands; C417552:lasiodiplodin; C030011:carbene; D015025:Zearalenone; D012428:Ruthenium; D008697:Methane