Miao, X.; Dixneuf, P.H.; Fischmeister, C.; Bruneau, C. “A green route to nitrogen-containing groups: the acrylonitrile cross-metathesis and applications to plant oil derivatives.” Green Chem., 2011, 13, 2258-2271.
A straightforward route to organonitriles, versatile intermediates in organic synthesis, would be cross metathesis (CM) with acrylonitrile. Unfortunately, acrylonitrile is definitely not the best substrate for metathesis reactions. Electron deficient olefins are generally difficult substrates for metathesis reactions, but α,β-unsaturated esters, aldehydes and ketones can be crossed with terminal olefins in good yields using second-gen Grubbs catalyst. Acrylonitrile is less reactive under these conditions, probably due to the strong ability of the nitrile group to coordinate to the metal and decompose the catalyst.
One of the first successful CM reactions with acrylonitrile was reported in 1995 using a Mo-catalyst, but required high catalyst loadings and the yields weren’t the best.
Most Grubbs catalysts failed miserably in the CM of acrylonitrile with different substrates. Second-gen Hoveyda catalyst performed better, but high catalyst loadings were required and the outcome of the reaction depended a lot on the cross partner. It’s noteworthy that, independent of the catalyst used, more of the Z-olefin was formed in contrast to all other electron deficient substrates which show a high degree of E-selectivity. Fast initiating catalysts such as bis(3-bromopyridine) and mono(2-methylpyridine) second-gen catalysts were comparable to the Hoveyda.
Crosses with acrylonitrile with different partners were studied in the Blechert group in 2001. Most reactions gave decent yields of the cross products with the second-gen Hoveyda, but the catalyst loadings were pretty high (5-8%). Even methacrylonitrile produced the trisubstituted olefin in good yields. The reaction is very selective; a mixture of acrylonitrile and methyl acrylate produced almost exclusively the nitrile cross product. Usually no dimerization of the acrylonitrile was observed and very little of the homocoupled cross partner was formed with excess of acrylonitrile.
Using additives such as CuCl or Ti(OPri)4 improved significantly the yields of acrylonitrile cross products with the Grubbs second-gen catalyst. Increases of 20-30% were seen when 20mol% Ti(OPri)4 was used as an additive. For the first time, even an internal olefin was crossed in the presence of CuCl in 57% yield. It turned out that the concentration of the reaction mixtures was crucial for the outcome of the cross reactions: decreasing the concentration from 0.5M to 0.07M more than doubled the yield with the Hoveyda second-gen catalyst. Microwave irradiation was also found to increase the yields of the reaction.
CM of unsaturated fatty acid derivatives from plant oils with acrylonitrile offers the possibility of producing high value added products from renewable resources but, due to the difficulties even with simple olefins, was not attempted until recently. High temperature, low concentration and excess of acrylonitrile were necessary to achieve high yields. Once again the second-gen Hoveyda catalyst performed best. Adding the catalyst using a syringe pump allowed for the catalyst loadings to be decreased to 0.025mol% for the CM of methyl undec-10-enoate with acrylonitrile. No self metathesis of the methyl-10-undecenoate was observed under the reaction conditions.
CM of an internal olefin with acrylonitrile using the syringe pump addition method gave 88% yield of the desired functional nitrile compound. Even though some of the ethenolysis product was formed under these conditions, the catalyst loading was remarkably low for a cross between an internal olefin and acrylonitrile (0.05mol%). Even the cross between fumaronitrile and the same internal olefin worked very smoothly with 5mol% catalyst, however only 50% conversion was reached with 1 mol% catalyst.
The Green Chemistry review shows how the development of new metathesis catalysts and careful optimization of the reaction conditions can give good results with even the toughest substrates. There is still room for improvement, but CM with acrylonitrile has turned into a valuable route to produce organonitrile compounds.