Nitro-Substituted Hoveyda−Grubbs Ruthenium Carbenes:  Enhancement of Catalyst Activity through Electronic Activation

Abstract

The design, synthesis, stability, and catalytic activity of nitro-substituted Hoveyda-Grubbs metathesis catalysts are described. The highly active and stable meta- and para-substituted complexes are attractive from a practical point of view. These catalysts operate in very mild conditions and can be successfully applied in various types of metathesis [ring-closing metathesis, cross-metathesis (CM), and enyne metathesis]. Although the presence of a NO(2) group leads to catalysts that are dramatically more active than both the second-generation Grubbs's catalyst and the phosphine-free Hoveyda's carbene, enhancement of reactivity is somewhat lower than that observed for a sterically activated Hoveyda-Grubbs catalyst. Attempts to combine two modes of activation, steric and electronic, result in severely decreasing a catalyst's stability. The present findings illustrate that different Ru catalysts turned out to be optimal for different applications. Whereas phosphine-free carbenes are catalysts of choice for CM of various electron-deficient substrates, they exhibit lower reactivity in the formation of tetrasubstituted double bonds. This demonstrates that no single catalyst outperforms all others in all possible applications.

Ruthenium‐Catalyzed Ring‐Closing Metathesis: Recent Advances, Limitations and Opportunities

“…Direct comparison of the merits of these catalysts versus C35, C38, and C39 is hampered by differences in substrate and reaction conditions. Highly suggestive, however, is the finding that RCM of 27 (Scheme 18) via C41b or C42a requires 40 minutes or one hour, respectively, to proceed to 95-99% completion, under conditions comparable to those noted for C39 above [110]. The activity of C39 thus appears greater than any other Ru metathesis catalyst developed to date, within the range of substrates explored.…”

“…Catalyst C42a achieved up to 76% yield in RCM of 29 within 2 h at 40 ˚C (2.5 mol %) [110]. Tetrasubstituted olefins are more difficult targets: under similar conditions, but double the catalyst loading, yields of 32 were <10% for C40, C41b and C42a after 24 h, vs. 14% for C2b.…”

“…Our purpose in this section is to trace some of the major current themes in design of new ruthenium catalysts, rather than to undertake a comprehensive review. Overviews of recent developments in the design of individual catalyst classes have appeared elsewhere [32][33][34][35][36][108][109][110].…”

“…Initiation of C40 itself is slow, despite the low oxophilicity of Ru(II), owing to the high thermodynamic stability of the five-membered chelate ring. Improved turnon efficiency was achieved by steric (C41 [133,134]) or electronic (C42 [109,110,135]) destabilization of the chelate.…”

“…Substrates bearing terminal olefins were rapidly cyclized to five-to sevenmembered rings under mild conditions (0-23 ˚C, 1 mol % Ru) [109,110,[133][134][135]; slightly greater activity was generally manifested by C41b [110]. The substrates shown in Scheme 19 proved more challenging.…”