Electric Literature of C27H39ClN2On October 5, 2021 ,《Activated Hoveyda-Grubbs Olefin Metathesis Catalysts Derived from a Large Scale Produced Pharmaceutical Intermediate – Sildenafil Aldehyde》 was published in Advanced Synthesis & Catalysis. The article was written by Monsigny, Louis; Piatkowski, Jakub; Trzybinski, Damian; Wozniak, Krzysztof; Nienaltowski, Tomasz; Kajetanowicz, Anna; Grela, Karol. The article contains the following contents:
Two EWG-activated Hoveyda-Grubbs-type ruthenium complexes (Sil-II and Sil-II’) were obtained, characterized, and screened in a set of olefin metathesis reactions. These catalysts were conveniently synthesized from a com. available pharmaceutical building block – Sildenafil aldehyde – in two steps only. Stability and catalytic activity tests disclosed that the bulkier NHC-ligand bearing catalyst Sil-II’ is visibly more stable and productive than its smaller NHC-analog Sil-II. Good application profile of catalyst Sil-II’ was confirmed in a set of diverse metathesis reactions including ring-closing metathesis (RCM) and cross-metathesis (CM) of complex polyfunctional substrates of medicinal chem. interest, including a challenging macrocyclization of the Pacritinib precursor. Compatibility of the new catalyst with various green solvents was checked and metathesis of Sildenafil and Tadalafil-based substrates was successfully conducted in acetone. The mechanism of Sil-II’ initiation has been investigated through kinetic experiments unveiling that the decrease of the steric hindrance of the chelating alkoxy moiety (from iPrO to EtO) favors the interchange initiation pathway over the typical dissociation pathway for other popular 2nd generation Hoveyda-Grubbs catalysts. The results came from multiple reactions, including the reaction of 1,3-Bis(2,6-diisopropylphenyl)-4,5-dihydro-1H-imidazol-3-ium chloride(cas: 258278-25-0Electric Literature of C27H39ClN2)
1,3-Bis(2,6-diisopropylphenyl)-4,5-dihydro-1H-imidazol-3-ium chloride(cas: 258278-25-0) may be used as a precursor to the free carbene 1,3-bis(2,6-diisopropylphenyl)-2-imidazolidinylidene, and also used as an in situ formed catalyst in a variety of reactions, e.g. amination, Heck coupling reaction, the ring-opening metathesis polymerization (ROMP), hydrogenation.Electric Literature of C27H39ClN2In addition, it can efficiently catalyze the Suzuki-Miyaura coupling of aryl chlorides with aryl boronic acids.
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem