Chelate-Assisted Ring-Closing Metathesis: A Strategy for Accelerating Macrocyclization at Ambient Temperatures

Abstract

Ring-closing metathesis (RCM) offers versatile catalytic routes to macrocycles, with applications ranging from perfumery to production of antiviral drugs. Unwanted oligomerization, however, is a long-standing challenge. Oligomers can be converted into the cyclic targets by catalysts that are sufficiently reactive to promote backbiting (e.g., Ru complexes of N-heterocyclic carbenes; NHCs), but catalyst decomposition limits yields and selectivity. Incorporation of a hemilabile o-dianiline (ODA) chelate into new catalysts of the form RuCl(NHC)(ODA)(=CHPh) accelerates macrocyclization, particularly for dienes bearing polar sites capable of H-bonding: it may also inhibit catalyst decomposition during metathesis. Significant improvements relative to prior Ru-NHC catalysts result, with fast macrocyclization of conformationally flexible dienes at room temperature.

Sequential Alkene Isomerization and Ring‐Closing Metathesis in Production of Macrocyclic Musks from Biomass

“…A very important fact in favour of the RCM reaction of isomerized dienes is that much lower levels of by‐products (cyclic dimers and oligomers) were formed during metathesis. This can be rationalized by the fact that the internal double bonds are generally less reactive in metathesis, so are less likely to create dimeric and oligomeric side products …”

“…In our tests, the commerciallya vailablem etathesis catalyst F [29] was used (for the structure see Scheme 1). [35,36] All dienes with at least one isomerised doubleb ond have undergone ring closing metathesisw ith satisfactory yields of 84-86 %. [30] Based on various examples of RCM macrocyclisations availableinl iterature, [31][32][33] we chose to keep the substrate concentration near 1.5 mm.A ccordingt ot he general optimized procedure, we performed several RCM reactions obtaining macrocyclic lactones with different ring sizes (Table 3), varying from 15 to 19 atoms.…”

“…This can be rationalized by the fact that the internal double bonds are generally less reactive in metathesis, so are less likely to create dimerica nd oligomeric side products. [35,36] All dienes with at least one isomerised doubleb ond have undergone ring closing metathesisw ith satisfactory yields of 84-86 %. Only in the case of dienes with less reactive trisubstituted CÀCd ouble bonds (7a and 8a)l ower yields were observed.…”

Volume intensified dilution of a ring‐closing metathesis in ethyl acetate by means of a membrane‐assisted process in solvent recycle

“…Indeed, Fogg and co‐workers reported oligomers as intermediates in RCM reactions. However, despite the fact that this equilibrium ring‐closing metathesis (ERCM) can potentially be expoited during the synthesis of macrocycles there is often still the necessity to use high dilution conditions …”

“…However, despite the fact that this equilibrium ring-closing metathesis (ERCM) 15 can potentially be expoited during the synthesis of macrocycles there is often still the necessity to use high dilution conditions. 16,17 Reducing the amount of waste from industrial chemical production is of fundamental importance both from an environmental and an economic point of view. Because 80% to 90% 18 of the reaction mass and a significant portion of energy use can be directly attributed to solvents, a reduction of the quantites used can have a significant effect on emissions, 19 economics and health and safety issues related to a chemical macrocyclization process.…”