Acrylonitrile metathesis

In 1995 Crowe and co-workers underlined the potential of the molybdenum alkylidene 3 as a catalyst for cross-metathesis when they reported the first examples of productive acrylonitrile metathesis [27] (for example Eq. 10). 

Case Study Developing a Ruthenium-Carbene Catalyst for Acrylonitrile Metathesis... 

Recently, a few examples of the metathesis of alkenes carrying functional groups have been reported. According to a patent, acrylonitrile reacts with propene to crotononitrile (cis and trans) and ethene 10) ... 

A first evaluation of complex 71a by Blechert et al. revealed that its catalytic activity differs significantly from that of the monophosphine complex 56d [49b]. In particular, 71a appears to have a much stronger tendency to promote cross metathesis rather than RCM. Follow-up studies by the same group demonstrate that 71a allows the cross metathesis of electron-deficient alkenes with excellent yields and chemoselectivities [50]. For instance, alkene 72 undergoes selective cross metathesis with 3,3,3-trifluoropropene to give 73 in excellent yield and selectivity. Precatalyst 56d, under identical conditions, furnishes a mixture of 73 and the homodimer of 72 (Scheme 17) [50a]. While 56d was found to be active in the cross metathesis involving acrylates, it failed with acrylonitrile [51]. With 71a, this problem can be overcome, as illustrated for the conversion of 72—>74 (Scheme 17) [50b]. 

Previously acrylonitrile had proved to be inert towards transition metal catalysed cross- and self-metathesis using ill-defined multicomponent catalysts [lib]. Using the molybdenum catalyst, however, acrylonitrile was successfully cross-metathesised with a range of alkyl-substituted alkenes in yields of40-90% (with the exception of 4-bromobut-l-ene, which gave a yield of 17.5%). A dinitrile product formed from self-metathesis of the acrylonitrile was not observed in any of the reactions and significant formation (>10%) of self-metathesis products of the second alkene was only observed in a couple of reactions. 

Like styrene, acrylonitrile is a non-nucleophilic alkene which can stabilise the electron-rich molybdenum-carbon bond and therefore the cross-/self-metathe-sis selectivity was similarly dependent on the nucleophilicity of the second alkene [metallacycle 10 versus 12, see Scheme 2 (replace Ar with CN)]. A notable difference between the styrene and acrylonitrile cross-metathesis reactions is the reversal in stereochemistry observed, with the cis isomer dominating (3 1— 9 1) in the nitrile products. In general, the greater the steric bulk of the alkyl-substituted alkene, the higher the trans cis ratio in the product (Eq. 11). 

The success of the cross-metathesis reactions involving styrene and acrylonitrile led to an investigation into the reactivity of other Ji-substituted terminal alkenes [27]. Vinylboranes, enones, dienes, enynes and a,p-unsaturated esters were tested, but all of these substrates failed to undergo the desired cross-metathesis reaction using the molybdenum catalyst. 

Cross-metathesis reactions with styrenes or acrylonitrile gave yields and cist trans selectivities that were comparable with the best results obtained in the previous reports (for example Eq. 12). 

The ratio of cross-/self-metathesis products, with respect to the alkyl-substituted alkene, was generally poorer (typically 3 1) than the analogous reactions with styrene or acrylonitrile, probably due to the absence of a good alkylidene stabilising substituent on either alkene and the closer nucleophilicities of the two substrates. 

Although the Grubbs ruthenium benzylidene 17 has a significant advantage over the Schrock catalyst 3 in terms of its ease of use, the molybdenum alkylidene is still far superior for the cross-metathesis of certain substrates. Acrylonitrile is one example [28] and allyl stannanes were recently reported to be another. In the presence of the ruthenium catalyst, allyl stannanes were found to be unreactive. They were successfully cross-metathesised with a variety of alkenes, however, using the molybdenum catalyst [39] (for example Eq. 20). 

A subsequent publication by Blechert and co-workers demonstrated that the molybdenum alkylidene 3 and the ruthenium benzylidene 17 were also active catalysts for ring-opening cross-metathesis reactions [50]. Norbornene and 7-oxanorbornene derivatives underwent selective ring-opening cross-metathesis with a variety of terminal acyclic alkenes including acrylonitrile, an allylsilane, an allyl stannane and allyl cyanide (for example Eq. 34). 

The examples listed in Table 3.21 illustrate the synthetic possibilities of cross metathesis. In many of the procedures reported, advantage is taken of the fact that some alkenes (e.g. acrylonitrile, styrenes) undergo slow self metathesis only. Interestingly, it is also possible to realize cross metathesis between alkenes and alkynes (Table 3.21, Entries 11-13), both in solution and on solid supports [927,928]. 

The stereoselectivity of olefin formation is crucial to the utility of CM. To date, a general metathesis catalyst capable of effecting diastereomeric control over a broad range of substrates has yet to be realized. Of particular interest is the development of a Z-selective catalyst, as Z olefins are a prevalent structural motif within both natural products and pharmaceutical agents.Current examples of Z-selective olefin CM have proved to be substrate dependent. These include the CM of enynes with alkenes, acrylonitrile the CM reaction... 

The CM of olefins bearing electron-withdrawing functionalities, such as a,/ -unsaturated aldehydes, ketones, amides, and esters, allows for the direct installment of olefin functionality, which can either be retained or utilized as a synthetic handle for further elaboration. The poor nucleophilicity of electron-deficient olefins makes them challenging substrates for olefin CM. As a result, these substrates must generally be paired with more electron-rich crosspartners to proceed. In one of the initial reports in this area, Crowe and Goldberg found that acrylonitrile could participate in CM reactions with various terminal olefins using catalyst 1 (Equation (2))." Acrylonitrile was found not to be active in secondary metathesis isomerization, and no homodimer formation was observed, making it a type III olefin. In addition, as mentioned in Section 11.06.3.2, this reaction represents one of the few examples of Z-selectivity in CM. Subsequent to this report, ruthenium complexes 6 and 7a were also observed to function as competent catalysts for acrylonitrile... 

The compound (dppe)PtMe(OMe),256 which is prepared by a metathesis reaction involving NaOMe and (dppe)PtMe(Cl) in a mixed benzene/methanol solvent system (dppe = bis(l,2-di-phenylphosphino)ethane), does not react with ethylene or pentene but does react with activated alkenes such as acrylonitrile, methylacrylate and fluoroalkenes. The reaction involving tetrafluoro-ethylene has been shown to give (dppe)PtMe(CF2CF2OMe), providing the first example of an alkene insertion into an M—OR bond.256 Interestingly, no insertion into the Pt—Me bond was observed. 

Where there is no spacer group between the C=C bond and the functional group, productive self-metathesis does not occur, but cross-metathesis reactions with other olefins are still possible. Recent impressive examples of this are the cross-metathesis reactions of acrylonitrile (equation 19). The reaction occurs with a wide variety of R groups. For 15 different compounds the yield of the new nitrile after 3 h at room temperature is 40-90%, with the cis isomer always strongly preferred (75-90%). Only minor amounts of RCH2CH=CHCH2R are formed, and no NCCH=CHCN182. The fact that acrylonitrile... 

The results of some cross-metathesis experiments for a series of nitriles CH2=CH(CH2) CN reacting with c -hept-3-ene are summarized in Table 4. No crossmetathesis occurs with acrylonitrile (n = 0). For n = 1, 2, 5, 8, 9 cross-metathesis products are formed in substantial amount, but for n = 3, 4 very little reaction occurs, an effect which is attributed to intramolecular coordination of the nitrile group to the metal centre in [Mt]=CH(CH2) CN (n = 3, 4), thereby reducing its metathesis activity or causing its destruction. With n > 5 the nitrile group has little influence on the reaction and its self-metathesis is preferred over that of hept-3-ene, whereas the reverse is true for n = 1,2. 

Vinyl chloride, like acrylonitrile, is not able to self-metathesize but will cross-metathesize with simple alkenes190,191. Both allyl chloride and allyl bromide will undergo metathesis on l CVAEOs/RjSn with good conversion and high selectivity192,193. 

Cross-metathesis of two different alkenes 11 and 42 usually produces a mixture of products 6 and 15. However, depending on the functional groups R1 and R2, the cross-product 6 is obtained with high selectivity rather than the homoproduct 15 from 11 and 42. Some terminal alkenes, such as allylstannane [16], acrylonitrile [17,18] and allylsilane [19], undergo clean cross-metathesis to give cross-products 6 as the main product, rather than homoproducts 15. Cross-metathesis of the cyclic alkenes 43 with terminal alkenes 42 can be used for the synthesis of dienes 44. 

The Mo-catalysed cross-metathesis of acrylonitrile (59) [17,18] and allylsilane (60) [19] with alkenes 61 and 62 produced cross-products 63 and 64 with high selectivity. Reaction of 1-octene with 2 equivalents of styrene (65) afforded 66 in 89% yield. Only small amounts of stilbene (68) and 67 as the homoproducts were formed [23]. 

To achieve selectivity in these reactions, a steric or electronic bias is required to favour one particular product or (more importantly given the reversible nature of CM) one metal-alkylidene precursor in the catalytic cycle.1 In particular, it has been known for some time that metathesis reactions involving one highly electron deficient olefin partner can be selective (for the first example using acrylonitrile or styrene and 1 see Ref. [40]) however,readily available potential substrates such as enones, acrylates and acrylamides are generally incompatible with either 1 or 2 (for two reported exceptions see Ref. [41]). This was partially overcome by the use of acrolein acetals as a,/i-unsaturated car-... 

Figure 6.5 The olefin metathesis reaction of acrylonitrile with Ru-4.

Scheme 7 Cross metathesis of allylbenzene and acrylonitrile with catalysts bearing N-aryl, N -alkyl NHCs...

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