Elsevier

Applied Catalysis A: General

Volume 486, 22 September 2014, Pages 94-104
Applied Catalysis A: General

Synthesis of α,β-unsaturated aldehydes and nitriles via cross-metathesis reactions using Grubbs’ catalysts

https://doi.org/10.1016/j.apcata.2014.08.032Get rights and content

Highlights

  • Ru-catalysed cross-metathesis of electron-deficient olefins successfully carried out.

  • Aldehydes/nitriles relevant to the fragrance industry prepared with good selectivity.

  • Valuable intermediates derived from 2-allyloxy-6-methylheptane have been prepared.

Abstract

A series of α,β-unsaturated aldehydes and nitriles of significant interest in the fragrance industry have been prepared using Grubbs’ catalysts in cross-metathesis reactions of electron-deficient olefins (i.e., acrolein, crotonaldehyde, methacrolein, and acrylonitrile) with various 1-alkenes, including 1-decene, 1-octene, 1-hexene and 2-allyloxy-6-methylheptane. The latter is of particular interest, as it has not previously being used as a substrate in cross-metathesis reactions and allows access to valuable intermediates for the synthesis of new fragrances. Most reactions gave good selectivity of the desired CM product (≥90%). Detailed optimisation and mechanistic studies have been performed on the cross-metathesis of acrolein with 1-decene. Recycling of the catalyst has been attempted using ionic liquids.

Introduction

α,β-Unsaturated aldehydes and nitriles are of significant interest in the fragrance and flavour industries, either by themselves or as key intermediates in the preparation of other synthetic scents [1]. They are also important intermediates in numerous organic processes, such as Diels Alder reactions [2], Michael additions [3] or aldol condensations [4], to name a few. Wittig-type reactions are commonly used to prepare α,β-unsaturated aldehydes and nitriles [5], but a variety of other methods have also been reported, including, for example, catalytic oxidation of allylic alcohols [6], Ru-catalysed isomerisation of propargylic alcohols [7], or synthesis via Grignard reagents [8]. In addition, cross-metathesis (CM) reactions have been applied to prepare α,β-unsaturated aldehydes and nitriles, but this route is still relatively unexplored, in particular with substrates containing electron deficient double bonds such as acrolein and related α-carbonyl compounds [9]. It should be noted that synthetic routes involving cross-metathesis have been shown to be advantageous over more conventional methods. For example, they allow direct access to chiral pharmaceutical intermediates without the need for a chiral resolution step [9c].

It has been established that α,β-unsaturated aldehydes and nitriles do not react with Grubbs’ first generation catalyst (1, Chart 1) [10], but are able to react in cross-metathesis reactions using ruthenium catalysts with NHC ligands (e.g., 23 in Chart 1). This is attributed to the greater electron donating ability of the NHC ligand compared to tricyclohexylphosphine (PCy3) [10a]. Thus, good yields of CM products using NHC-Ru catalysts have been reported, for example, in reactions involving acrolein, methacrolein, acrylic acid, crotonaldehyde or acrylates [9], [11]. Cross-metathesis reactions using acrylonitrile as substrate are more common and include processes using Schrock's molybdenum catalyst [12], as well as a variety of NHC-ruthenium catalysts [9], [13]. As in the case of acrolein, acrylonitrile shows poor reactivity with catalyst 1 [10], [13]. Some of these reactions have been reported to work in neat conditions [11].

Selective formation of the cross-metathesis product can be achieved by combining an olefin that shows slow or no self-metathesis (classified as Type II/III olefins) with an olefin able of fast self-metathesis or Type I (e.g., 1-alkenes; see Scheme 1) [14]. In these reactions, the Type I homo-dimer may form initially [Scheme 1(b)], but undergoes secondary metathesis with the Type II/III olefin to produce the desired CM product [Scheme 1(c)]. Although the classification of a particular olefin depends on the catalyst, acrolein and related compounds, including acrylonitrile, are generally classified as Type II or Type III olefins [14].

Ruthenium-catalysed cross-coupling reactions with terminal olefins almost always occur with a high degree of E-selectivity [15], although strategies to favour Z-selectivity have been developed [16]. Acrylonitrile, however, generally produces cross-metathesis products where the Z isomer is predominant, and it has been proposed that this Z-stereoselectivity must be kinetically controlled and most likely related to the small size and/or electron-withdrawing properties of the cyano group [12], [13], [17]. A few examples in which cross-metathesis reactions of acrylonitrile have produced the E-isomer as the major component have also been reported [18].

In order to improve recyclability of Grubbs’ catalysts, ionic liquids (ILs) have been used as reaction media or for the immobilisation of the catalyst onto silica (e.g., using the ‘supported ionic liquid phase’ or SILP concept) [19]. For example, Grubbs’ second generation catalyst 2 has shown enhanced activity in CM reactions in ionic liquids, compared to dichloromethane [20], and Hoveyda-Grubbs’ type catalysts immobilised onto silica gave excellent yields in RCM metathesis reactions [19a]. In both cases, the catalysts could be easily recycled up to four times. In addition to conventional Grubbs’ catalysts, ionic analogues have been developed (e.g., complex 4 in Chart 1) with the aim of increasing the catalyst's retention time in the ionic liquid, thus improving its recyclability and reducing leaching into the organic phase [21].

In this paper, a series of α,β-unsaturated aldehydes and nitriles of significant interest in the fragrance industry have been prepared using Grubbs’ catalysts in cross-metathesis reactions of electron-deficient olefins (i.e., acrolein, crotonaldehyde, methacrolein, and acrylonitrile) with various 1-alkenes. Detailed kinetic and mechanistic studies have been performed on the cross-metathesis of acrolein with 1-decene and attempts to recycle the catalyst by using ILs are also reported. Of particular interest are the reactions using 2-allyloxy-6-methylheptane, as this substrate has not previously being used in cross-metathesis. The product from its reaction with acrolein, 6,10-dimethyl-5-oxoundec-2-enal, is of use in the synthesis of a novel fragrance material [22].

Section snippets

Catalyst preparation

Catalysts 13 were obtained from Aldrich and used as received. Ionic catalyst 4 was synthesised following a literature procedure [21e]. The ionic liquids were prepared as described elsewhere [23]. Catalysts and ionic liquids were handled and stored in a glovebox.

Cross-metathesis between acrolein and 1-decene

The cross-metathesis reaction of acrolein and 1-decene was studied in the first instance (Scheme 2). The effect of varying the catalyst, solvent, concentration of 1-decene and ratio of starting materials was analysed. The results are summarised in Table 1. In all cases, the reactions yielded the cross-metathesis (CM) product, undec-2-enal (normally as the major product), together with the self-metathesis (SM) product of 1-decene (octadec-9-ene). As expected, self-metathesis of acrolein was not

Conclusions

The Ru-catalysed cross-metathesis reaction of acrolein and 1-decene has been studied in detail. Overall, the best results (81% yield of undec-2-enal, 99% selectivity, 88% conversion of 1-decene) have been obtained in dichloromethane using catalyst 3 at relatively low loading (1.4 mol%) and added gradually over a period of 3 h (see Table 2, entry 2c). It is interesting to note that, in contrast with previous studies, using excess of acrolein in the reactions did not significantly affect the

Acknowledgments

The authors acknowledge support from QUILL. S.M.R. acknowledges support from the Department of Education and Learning in Northern Ireland and Givaudan SA. The authors thank Dominique Lelievre and Alain Alchenberger (Givaudan SA) for odour assessments.

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