Acrylonitrile cross-metathesis

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). 

Crowe WE, Goldberg DR. Acrylonitrile cross-metathesis -coaxing olefin metathesis reactivity fiom a reluctant substrate. J Am Chem Soc 1995 117 5162-5163. 

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]. 

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). 

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). 

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]. 

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. 

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]. 

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

Another example that the successfiil discovery of new reactions may effect fine chemical synthesis is the selective cross-metathesis of acrylonitrile with terminal olefins to give substituted acrylonitriles. This is the first time that an olefin functionalized directly at the double bond undergoes cross-metathesis. ... 

Cross-metathesis. Functionalization of terminal alkenes by the metathetic method using catalyst 1 has been well established. The reaction between styrene and vinylsilanes gives (o-silylstyrenes, between allylarenes and acrylonitrile leads to 4-aryl-2-butenonitriles. Alternatively, homo-metathesis of two allylarene molecules to give 1,4-diary 1-2-butene is first carried out and the cross-metathesis follows. Also of interest is the homo-metathesis of monosubstituted allenes to symmetrical allenes. ... 

In early work, Crowe showed that an a-olefin would undergo selective cross metathesis with acrylonitrile, styrene, and vinylsilanes in the presence of Schrock s molybdenum... 

The Grubbs pyridine solvates are the fastest initiators of alkene metathesis and are valuable as synthetic intermediates to prepare other ruthenium carbene complexes. In particular, the 18-electron pyridine solvates 4a,b are very fast initiators that were developed to catalyze difficult alkene metatheses (e.g., the cross metathesis of acrylonitrile) [6]. The rates of initiation for several complexes are provided in Table 9.9. The pyridine solvate 4a has been found to initiate about 105 times faster than the parent Grubbs complex 2 and at least 100 times faster than the second-generation triphenylphosphine variant 26. When compared with the Hoveyda-Blechert complex 3a, 4a initiated about 100 times faster (c entry 3 vs. entry 5). The bromopyridine solvate 4b exceeded all of these in its initiation rate it was at least 20 times more reactive than 4a. 

Scheme 12.23 Cross metathesis of acrylonitrile and functionalized olefins using TifOi-Prj as an additive.

This complex was evaluated in a series of test reactions and compared to 3 and 6. It showed in most cases a higher activity than the above-mentioned complexes with excellent stability. Catalyst 20 was found to be particularly efficient for cross-metathesis (CM) reactions involving acrylonitrile (Scheme 13). 

Crowe and Goldberg and Grubbs et al. have found conditions under which cross-metathesis (CM) of two different monoalkenes can give good selectivity for the desired cross-dimer over other products. Equation 14.95 shows an example that relies on the fact that acrylonitrile is inactive for self-metathesis but t es part in the cross-reaction. Differential reactiviQr of different carbene intermediates is also responsible for the selectivity of ring-opening metathesis Eq. 14.96 shows a ROM example by Snrqrper et al. Asymmetric ROM catalysis is also possible. ... 

Love, J.A., Morgan, J.P., Tmka, T.M., and Grubbs, R.H. (2002) A practical and highly active ruthenium-based catalyst that effects the cross metathesis of acrylonitrile Angewandte Chemie-Intemational Edition, 41,4035. 

Fig. 21 Z-Selective cross metathesis of acrylonitrile with terminal olefins...

In the same year the Crowe group reported the first example of Z-selective cross metathesis of acrylonitrile and various terminal olefins catalyzed by Schrock catalyst shown in Fig. 21 [48]. Acrylonitrile was required to achieve moderate to good Z-selectivities. A model that minimizes steric interaction between imido ligand of the catalyst and the substituent on the aUcene was proposed to account for the Z-selectivity. In 2001 the Blechert group reported that second-generation Hoveyda-Grubbs catalyst promoted similar reactions with essentially the same level of Z-selectivity (typically 4 1 Z E) [49]. 

Boddaert T, Coquerel Y, Rodriguez J. Microwaves-assisted cross-metathesis of acrylonitrile. Compt. Rend. Chim. 2009 12 872-875. 

Gessler S, Randl S, Wakamatsu H, Blechert S. Highly selective cross metathesis with acrylonitrile using a phosphine free Ru-complex. Synlett 2001 430-432. 

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. 

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. 

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. 

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