A practical larger scale preparation of second-generation hoveyda-type catalysts

Finding a subtle balance between the stability of the catalyst (and its insensitivity to impurities) and its high activity has been called one of the "Holy Grails" of catalysis. This is especially visible in the field of olefin metathesis: a fairly old reaction that has long remained as a laboratory curiosity without significance in advanced organic chemistry.(1) New ruthenium catalysts 1 and 2 (Figure 1), which combine high catalytic activity with fairly good stability, however, have revolutionized the field.(2-4) As a result, recent years have seen a tremendous development of research efforts in Ru catalyst design, driven by the fascinating challenge to improve the already impressive performances of the original Grubbs precatalyst 1 and 2. We have recently found that the 5-nitro-substituted Hoveydatype(5) catalyst 4b possesses a dramatically enhanced reactivity in model ring-closing (RCM), cross, (CM), and enyne metathesis.(6) Interestingly, the air and thermodynamic stability of 4b is not reduced as compared with the parent Hoveyda-Grubbs complex 3b.(7) As a result, 4b has found successful applications in the synthesis of alkaloids,(8a,b) antitumor,(8c,d) antiviral,(8e,f) and antifungal agents,(8g) and a porphyrin- fullerene dyad(8h) as well as porphyrin,(8i) sulfone,(8j) and azulene-containing building blocks,(8k) chiral phosphine ligand precursors,(81) and other ruthenium complexes.