Metathesis Transformations of Natural Products: Cross-Metathesis of Natural Rubber and Mandarin Oil by Ru-Alkylidene Catalysts

This study reports on the degradation of natural rubber (NR) via cross-metathesis with mandarin oil and d-limonene, an abundant compound in essential oils; that were used as chain transfer agents (CTAs) and green solvents. Reactions were performed in the presence of the ruthenium-alkylidene catalysts (PCy3)2(Cl)2Ru=CHPh (I) and (1,3-dimesityl-4,5-dihydroimidazol-2-ylidene) (PCy3)Cl2Ru=CHPh (II), respectively. Catalyst II bears an N-heterocyclic carbene ligand (NHC) bounded to the ruthenium atom, which has a strong basic character; therefore it is more active toward trisubstituted olefins in comparison with catalyst I. In both cases, isolated monoterpene-terminated isoprene oligomers were obtained as products of the cross-metathesis degradation of NR. In the presence of catalyst II molecular weight values around Mn × 102 and yields of 80% were obtained; whereas with catalyst I, the molecular weights of products were about Mn × 104 with yields ranging 70 to 74%. The composition and yield of NR degradation products were determined by GC/MS (EI) analysis and it was found that the oligomers obtained have primarily one vinyl group and one terpene-monocyclic group at the chain end, with isoprene units Am = 2, 3 y 4.


Introduction
Catalytic transformations of biobased molecules into useful chemicals have attracted great interest. Numerous renewable resources such as natural fats, oils and terpenes have been tested using metathesis reactions [1][2][3][4][5][6]. For example, monoterpenes such as d-limonene and β-pinene have been used as chain transfer agents for the ring-opening metathesis polymerization (ROMP) of cycloolefins [7,8]. Recently, β-pinene has been tested as a cross-metathesis partner for the degradation of natural rubber [9]. It is worth noting that several natural products such as natural rubber, terpenes, plant polyprenols and dolichols, among others, are trialkylsubstituted olefin-based compounds [10][11][12]. Trisubstituted olefins are challenging substrates for metathesis reactions and these molecules exhibit less reactivity as compared to disubstituted olefins [13]. Computational and experimental studies show that rutheniumalkylidene catalysts coordinated with the N-heterocyclic carbene (NHC) ligand are preferred for the metathesis of challenging highly functionalized substituted olefins [14,15]. Thus, computational modeling of (Z)-3-methyl-2-pentene metathesis using the first and second generation rutheniumalkylidene catalysts demonstrated that the activation energy of the metathesis by using the second generation Grubbs catalyst is lower than that of the first generation one due to the ability of the NHC to stabilizing the Ru center in a transition state [15]. A recent computational study of -pinene ringopening metathesis using the second generation Grubbs catalyst, tungsten based Schrock and Fischer type metal carbenes revealed the importance of the steric factors in both the metathesis catalyst and the monomer substrate. The successful catalyst for the metathesis of terpene structure-containing molecules should have small substituents at the metal active center and the carbon carbene atom. Thus, the lowest activation and reaction energies were found for methylene metalcarbenes [16].
The mandarin oil is extracted from Citrus reticulate of the Rutaceae family [17]. Mandarin, lemon and other citrus essential oils are very attractive plant based compounds for the metathesis reactions. The metathesis ability and the direct transformation of these terpene based oils via cross-metathesis reactions have been less studied [18].
Natural rubber is a linear polyterpene compound which is isolated from the latex of Hevea brasiliensis and other tropical plants [19]. Metathesis degradations of natural rubber via cross-metathesis with ethylene (ethenolysis) and functionalized olefins using the classical W-based catalyst as well as the rutheniumalkylidene coordinated with the N-heterocyclic carbene (NHC) ligand have been published [20][21][22][23].

Results and Discussion
The major constituents of mandarin oil are monoterpenes such as d-limonene (74%), γ-terpinene (15.6%) and α-pinene (4.2%). Terpenes such as d-limonene, contained in the mandarin oil, have in their structure carbon-carbon double bonds that are involved in the cross-metathesis reactions. Table 1 presents the composition of mandarin oil according to GS/MS (EI) analysis. It is worth noting that d-limonene, β-pinene and other monoterpenes during the cross-metathesis can undergo the isomerization and self-metathesis reactions to produce non-desired products [7,9]. The control experiments with mandarin oil in the presence of catalyst I at 45 °C during 24 h showed that d-limonene, γ-terpinene and α-pinene did not participate in the isomerization and self-metathesis reactions. The composition of mandarin oil after these control experiments was examined by GC/MS, 1 H-NMR ( 13 C-NMR).  Table 2 shows the results of the metathesis degradation of NR using d-limonene and mandarin oil as CTAs in the presence of ruthenium-alkylidene catalysts I and II. When NR was depolymerized via cross-metathesis with d-limonene in the presence of catalyst II, the oligomeric products had low molecular weights giving values around M n × 10 2 with yields ranging from 80 to 97% (entries 1-3). It is observed in Table 2, that oligomers with similar molecular weights were obtained using mandarin oil or d-limonene as CTAs (entries 1 and 9). Table 2 (entries 6-10) also describes the degradation of NR in the function of the time. The molecular weights of products decreased an order of magnitude over the period from 2 to 8 h (entries 6 and 7) until they reached an equilibrium, giving molecular weight values around M n × 10 2 and yield of 80% (entries 9 and 10).
The function of a CTA is to control the molecular weight by the NR/CTA molar ratio in the cross metathesis degradation. Table 2 shows the degradation of NR using NR/CTA molar ratios of 1:1, 5:1 and 10:1 (entries 9, 11 and 12).  On the other hand, mandarin oil and d-limonene were used as solvents in the degradation reaction of NR. It can be seen in Table 2 that when a large excess of mandarin oil or d-limonene (entries 3 and 4) is used, the degradation of NR proceeds with a similar efficiency as compared to the degradation when 1,2-dichloroethane is used as solvent (entry 5) to obtain low molecular weight products. The formation of terpene terminated isoprene oligomers was confirmed by 1 H and 13 C-NMR spectroscopy. Figure 1 presents the 1 H-NMR spectra of NR before (A) and after the degradation (B) using d-limonene as a CTA and catalyst II (entry 2). The spectrum (B) shows two new peaks of C=CH 2 protons of the terpene group at 4.68 and 4.71 ppm. It also, shows the signals of the isoprene proton (C=CH) at 5.12 ppm, and that corresponding to an olefin proton (C=CH) in the monocyclic terpene at 5.38 ppm. The signals of the aliphatic protons of d-limonene are observed at 1.1-1.4 ppm. As shown in Table 2, the experimental molecular weights of isoprene oligomers determined by gel permeation chromatography (GPC) and end-group analysis using 1 H-NMR spectroscopy were higher than the theoretical molecular weights, the latter can be attributed to intramolecular cyclization reactions of the polymer chains as well as the acyclic diene metathesis polymerization that takes place during the cross-metathesis of methylene terminated products [9]. According to the results shown in Table 2, the metathesis degradation of NR produces oligomers with molecular weight distributions close to 2. The molecular weight of products may be controlled by changing the molar ratio of NR to CTAs (Table 2, entries 9, 11 and 12).

Figure 1. 1 H-NMR (300 MHz, CDCl 3 ) spectra of NR before (A) and after (B) the cross-metathesis degradation with d-limonene.
Moreover, a study on the composition and yields of isolated oligomers obtained in the degradation via cross-metathesis of NR with d-limonene, using GC/MS (EI) analysis (entry 2) was carried out. The results indicated that the oligomers are formed by one unit of d-limonene attached to the end chain of the isoprene. The Scheme 2 shows the isolated products of this reaction A m (91%) and B m (6%) with m = 2, 3 and 4 isoprene units, respectively.

Products
It is worth noting that the formation of oligomers with terpene terminated groups at both sides was not detected. Further analysis of the cross-metathesis products demonstrated that the reaction proceeded with high selectivity leading to the desired products with monoterpene terminated groups A m . These results confirmed that the reaction degradation of NR in the presence of d-limonene as a CTA proceeded via the formation of less substituted intermediate in a transition state. A computational study regarding to a model compound of NR (Z)-3-methyl-2-pentene metathesis using rutheniumalkylidene catalysts revealed that the secondary metalcarbene active center is the principal reactive intermediate in this reaction due to the formation of less sterically hindered transition states. Scheme 3 shows the metathesis initiation reaction of (Z)-3-methyl-2-pentene mediated by ruthenium-alkylidene catalysts [15]. The highly substituted metalcyclobutane intermediate will show highest activation energy compared to those of unsubstituted or less substituted intermediates. The cross-metathesis degradation of NR is accompanied by the intramolecular cyclization reactions of the polymer chains giving the cyclic trimer trans,trans,trans-1,5,9-trimethyl-1,5,9-cyclododecatriene (C 15 H 24 , M = 204) with yield of 3%. This fact has been corroborated by experimental and computational studies, where the formation of the trans cyclic trimer is the most thermodynamically favored among all the cyclic molecules [23,24].

Degradation Procedure in Organic Solvents
Metathesis degradation of NR was carried out in a glass vial under a dry nitrogen atmosphere at different temperatures. After terminating the reaction by addition of a small amount of ethyl vinyl ether, the solution was poured into an excess of methanol. The oligomers obtained were dried under a vacuum.

Conclusions
Mandarin oil and d-limonene were successfully used as CTAs in the metathesis degradation of NR. Mandarin oil was also found to be very suitable as a green solvent and it can be used instead of 1,2-dichloroethane and other non-green solvents. Catalyst II depolymerized NR completely in comparison with catalyst I when the reactions were conducted in the same conditions. Molecular weights of products were controlled primarily by the NR/CTA molar ratio giving values around M n × 10 2 . The main products of the cross metathesis degradation of NR with mandarin oil were monoterpene terminated oligomers of series A m = 2, 3 and 4. Metathesis transformations of NR in the presence of mandarin oil allowed the synthesis of desired monoterpene-terminated products with higher selectivities than previously reported metathesis degradation procedures using -pinene as a cross-metathesis partner.