New Results on the Functionalization of Terminal Alkenes by Cross-metathesis Reactions

Abstract

The ruthenium-catalyzed reaction of allylbenzene with several types of alkene provides good yields of the cross-metathesis products regardless of the structural characteristics of the alkene.In the course of our research on sugars we wished to prepare the mannose derivative 4. Our first approach, involving a Wittig-Horner reaction between the aldehyde 1 and the stabilized anion of phosphonate 2, afforded very low yields whatever the base and reaction conditions used. We then decided to try an intermolecular cross-metathesis reaction 1 , despite the lack of precedents, because the necessary precursors are readly prepared. Compound 3 2 reacted with acrolein dimethyl acetal in the presence of 5% of Grubbs' catalyst (Cl 2 (PCy 3 ) 2 Ru = CHPh; Ru) to give compound 4 in 77% yield with a 20:1 E/Z ratio (Scheme 1) 3 .There is considerable uncertainty as to the factors that influence the selectivity of intermolecular metathesis reactions: some authors 4-6 suggest that electronic factors predominate, while others 7,8 seem to have found that steric parameters and the influence of neighbouring heteroatoms may be the most important determinants of high selectivity. In view of this, the finding that the reaction of Scheme 1 was highly selective for cross-metathesis, no self-metathesis products having been detected, led us to study this type of process more thoroughly. Using allylbenzene as reference alkene and two equivalents of the alkene partner, we found that the reaction proceeds crossselectively for a variety of olefins (Table 1) 9 . The results obtained with allyltrimethylsilane and allyloxytrimethylsilane are similar to those previously reported by other authors 10,11 . However, reports that electron-poor olefins do not participate in Ru-catalyzed cross-metathesis reactions 12,13 were not corroborated: on the contrary, we found that acrylonitrile and acrolein couple to allylbenzene with high cross-selectivity and in good yield. We also obtained good results with allylalcohol, allylacetamide and in particular allylbromide. The unprecedented achievement of cross-metathesis with this last reagent shows that the presence of a neighboring heteroatom is not strictly necessary for cross-selectivity 9 .Although both allylbenzene and the other olefins underwent self-metathesis when subjected to the reaction conditions in the absence of a partner 14 , no significant amounts of self-metathesis products were detected when the two partners were present in the above 1:2 ratio; as expected, when just one equivalent of the second olefin was used, the self-metathesis product of allylbenzene was obtained in 20% yield as well as the cross-metathesis product (39%). In conclusion, the cross-metathesis reaction is favoured under the reaction conditions described above, is not totally dependent on the structural characteristics of the alkenes, and constitutes a simple method for functionalization of a variety of terminal olefins. It should prove particularly useful for obtaining primary allylic bromides, a type of compound of great synthet...

Cross‐metathesis with acrylonitrile and applications to fatty acid derivatives

“…Among the less functionalized olefins, allylbenzene has been used as a model compound [6][7][8][9][10]. From Table 1, it appears that this reaction requires heating at 40 7C and that Grubbs I (2) and II (3) catalysts are not very efficient unless an excess of acrylonitrile or an additive such as CuCl is used.…”

“…This reaction was first reported in 1995 in the presence of the Schrock molybdenum catalyst [Mo(CHCMe 2 Ph)(NAr)][-OCMe(CF 3 ) 2 ] 2 1, which made the cross-metathesis with simple terminal alkenes and O-protected o-hydroxyalkenes possible in excellent yields [4]. The first-generation Grubbs catalyst RuCl 2 (=CHPh)(PCy 3 ) 2 2 generally exhibited a poor reactivity in cross-metathesis reactions with conjugated olefins such as acrylonitrile or acrolein [5], and the crossmetathesis of acrylonitrile with allylbenzene in 60% yield represents one of the rare examples of acceptable reactivity with this catalyst [6]. Then, the development of crossmetathesis with acrylonitrile and a variety of functional terminal olefins started with the introduction of Grubbs secondgeneration RuCl 2 (=CHPh)(PCy 3 )(N-heterocyclic carbene), and more robust Hoveyda-type catalysts.…”

Recent Developments in Olefin Cross‐Metathesis

“…The lack of material on this potentially important reaction would seem to point towards incompatibility; however, two reports have appeared which cast doubt on this conjecture, at least in the case of certain substrates. Castedo and Blanco [21] found that allylbenzene could efficiently react with a range of CM partners (2 equiv), including acrylonitrile or acrolein, in the presence of 6 (5 mol %). This report also detailed the first example of CM with allyl bromide catalyzed by 6.…”

“…If one sees a typical CM reaction as a competition between three reaction pathways, that is, selective CM or dimerization of either starting material, then if one partner dimerizes relatively slowly, the selectivity naturally increases. The first such report came from Grubbs and co-workers at Caltech, [32] who observed that CM between a,b-unsaturated compounds (esters, aldehydes, [33] and ketones [19][20][21][22][23][24] and simple terminal olefins 16-18 in the presence of 3 (5 mol %) in CH 2 Cl 2 at 45 8C proceeded in good to excellent yields with impressive E selectivity ( Table 2). In most cases, an excess of one olefin component is used to improve selectivity.…”

5.26 Cross Metathesis

“…The example of CM between allylbenzene, a type I olefin, and allyl bromide, promoted by Gru-I, was published by Castedo et al (Scheme 12). 31 Further improvements in terms of yield were made by using the more active Gru-II, 32,33 Hov-II, 34 and finally Est-II 35 catalysts. It was noted that the internal alkene 39 can act as a convenient replacement for the more volatile allyl chloride.…”