Efficient Conversion of Renewable Unsaturated Fatty Acid Methyl Esters by Cross-Metathesis with Eugenol.

Cross-metathesis of unsaturated fatty acid methyl esters (methyl oleate (MO), methyl petroselinate (MP), and methyl erucate (ME), obtained from vegetable oils) with eugenol (obtained from clove oil) proceeded under green, mild conditions (in 2-propanol or ethanol at 50 °C) in the presence of a ruthenium-carbene catalyst (called a second-generation Grubbs catalyst). These metathesis reactions proceeded with both high conversion (>90% of MO, MP) and selectivity (>98%) even with low catalyst loading (0.1 mol % Ru).

Introduction

Olefin metathesis has been known as an efficient method for synthesis of various intermediates and fine chemicals;[1−16] both cross-metathesis (CM) and ring closing metathesis have been employed especially for the purpose.[1−11] One of the recent promising applications in the olefin metathesis is the utilization of renewable bio-source materials to complement or replace petroleum-based specialty chemicals.[12−16] In particular, CM of unsaturated fatty acid esters (shown in Scheme ), which are obtained from plant oils or algae-derived feedstocks,[1−3,17−20] has been considered as a promising subject in terms of both green chemistry and oleochemistry.[12−16,21−41] Methyl oleate (MO) is the predominant component of fatty acid methyl esters of the triglycerides in many vegetable oils, such as olive, canola oil, or Jatropha oil,[17−20] and is usually obtained from the transesterification of vegetable oils with alcohol. Therefore, considerable attention has been paid for utilization of MO as the starting material for the production of intermediates and polymer precursors via CM.[30−41] For instance, CM of MO with functionalized olefins, such as allyl chloride,[32] methyl acrylate,[33,34] acrylonitrile,[35,36] allyl acetate,[37] allyl glycidyl ether, and allyltrimethylsilane (ATMS),[41] has been studied to obtain renewable α,ω-bifunctional compounds.

Scheme 1

Typical Unsaturated Fatty Acid Methyl Esters Derived from Plant Oils or Algae-Derived Feedstocks, and Eugenol (UG) Obtained from Biomass

Eugenol (UG), featuring a phenolic allyl benzene (shown in Scheme ), is also an interesting bio-based compound. UG is typically obtained from clove oil and has been widely used not only in foods, perfumes, and antioxidants but also in the medical and pharmaceutical fields, due to its unique properties in reducing blood sugar, triglyceride, and cholesterol.[42] UG can also be considered as a lignin derivative and be extracted potentially from lignocellulosic biomass. Moreover, UG can be easily converted to many types of chemicals owing to its bifunctional nature. The aliphatic chain and methoxy group (−OCH3) affect the physical properties of polymers derived from UG,[43−45] whereas the hydroxyl (−OH) group and the terminal olefin provide further chemical modification exemplified in designing polymer networks via thiol–ene coupling[46,47] or bis-maleimide networks,[48,49] particularly for performing metathesis reactions.[50] Therefore, reports concerning self-metathesis (SM)[50,51] and CM of UG with symmetrical internal olefins[13,52,53] and electron deficient terminal olefins (such as methyl acrylate, methyl methacrylate, acrylonitrile, and with acrylamides)[50,52] have been known in the presence of ruthenium catalysts.

The CM of unsaturated fatty acid methyl esters with UG should thus afford multifunctional products having hydrophobic (long alkyl chain length) and hydrophilic (phenolic group) properties and/or olefinic double bonds. These suggest that UG is the promising candidate as a substrate for the CM reaction with fatty acid methyl esters; however, comprehensive studies of CM (shown in Scheme ) still have not been conducted.

In this paper, we wish to introduce our explored results for CM of UG with a series of unsaturated fatty acid methyl esters having an internal double bond, such as MO, methyl petroselinate (MP), and methyl erucate (ME), and that having a terminal double bond (methyl 10-undecanoate, MU), in the presence of ruthenium-carbene catalysts (Scheme ). We herein present that these CM reactions proceed efficiently in ethanol, isopropanol, and dimethyl carbonate (DMC) (environmentally benign solvent) under sustainable conditions, although these reactions are often conducted either in chlorinated solvents (dichloromethane (DCM) and 1,2-dichloroethane)[54] or aromatic solvents (toluene, benzene, and chlorobenzene).[36,51] The influence of reaction conditions (such as time, temperature, substrate concentration, and ratio of UG/substrate) toward both activity and selectivity has been investigated in detail.

Scheme 2

Cross Metathesis (CM) of Eugenol (UG) with Methyl Oleate (MO) or Other Unsaturated Fatty Acid Methyl Esters

Results and Discussion

Cross Metathesis of Methyl Oleate (MO) with Eugenol (UG) Using Ruthenium Catalysts

MO has been chosen as a model substrate in this CM with UG using ruthenium-carbene catalysts (shown in Scheme , G1, G2, G3, and HG2). Greener solvents such as dimethyl carbonate (DMC), ethanol, and 2-propanol were chosen for the purpose of adopting environmentally benign conditions, although dichloromethane (DCM) or toluene was often used with these ruthenium catalysts. Table summarizes the selected results conducted under various conditions.a,b As shown in Scheme , four types of CM products (expressed as CM1, CM2, CM3, and CM4) as well as SM products can be considered in the reaction. 1H- and 13C NMR spectra of the CM products[50,55−57] are shown in Figures S17–S26 in the Supporting Information (SI).a,b

Table 1

Effect of Solvent and MO Concentration in Cross-Metathesis (CM) of Methyl Oleate (MO) with Eugenol (UG) by G2a

					metathesis products (%)e
run	solvent	UG (equiv)b	MO conc. (M)c	MO conv.d (%)	CM1	CM2	CM3	CM4	SM1 trans	SM1 cis	SM2 trans	SM2 cis	select.(1)f (%)	select.(2)g (%)	TONh
1	CH2Cl2 (DCM)	10	1.0	70	21	30	17	19	1	0	0	0	63	98	440
2	DMC	10	1.0	82	23	34	17	21	1	0	1	0	59	98	480
3	ethanol	10	1.0	60	14	23	15	18	1	0	0	0	61	98	370
4	2-propanol	10	1.0	94	34	46	16	19	1	0	1	0	63	98	590
5	nonei	10		41	12	16	11	12	1	0	0	0	63	98	260
6	DMC	10	4.0	42	8	13	9	10	1	0	0	0	48	97	200
7	ethanol	10	4.0	90	27	41	17	21	1	0	1	0	61	98	550
8	ethanol	10	10.0	91	31	48	17	21	1	0	1	0	65	98	590
9	ethanol	10	20.0	91	35	45	17	20	1	0	1	0	65	98	590
10	2-propanol	10	4.0	95	43	57	17	19	1	0	1	0	73	98	690
11	2-propanol	10	10.0	84	33	43	19	22	1	0	1	0	71	98	600
12	2-propanol	10	20.0	85	34	44	19	22	1	0	1	0	71	98	600

Conditions: 2.00 mmol of MO, catalyst (G2) 0.002 mmol (0.1 mol %), temperature 50 °C, reaction time 10 min.

Based on MO.

Initial MO conc. in solvent.

Conversion of MO estimated by gas chromatography (GC) using an internal standard (IS).

GC yield estimated according to the effect of carbon number (ECN) rule.

Selectivity of CM1–4 and SM1,2 based on the conversion of MO.

Selectivity of CM products (%) = (CM1 + CM2 + CM3 + CM4)/(CM1 + CM2 + CM3 + CM4 + SM1 + SM2). CM1: dec-1-ene, CM2: methyl dec-9-enoate, CM3: 2-methoxy-4-(undec-2-en-1-yl)phenol, CM4: methyl 11-(4-hydroxy-3-methoxyphenyl)undec-9-noate, SM1: octadec-9-ene, SM2: dimethyl octadec-9-enedioate.

Turnover number (TON) = molar amount of metathesis product from MO (on the basis of MO conv. and select.(1))/Ru (mol).

Conducted without solvent (MO and UG). Detailed analysis data are shown in the Supporting Information (SI).a,b

It should be noted that the high conversions of MO have been attained under mild conditions (50 °C) even for a short reaction period (10 min), when the reaction was conducted in the presence of G2 (Table , runs 1–4).b Importantly, the MO conversion carried out in DCM was relatively close to those carried out in DMC and 2-propanol.b Moreover, the selectivity of CM and SM products (defined as select.(2)) in DMC, ethanol, and 2-propanol is almost identical to that in DCM; the selectivity of CM and SM products reached almost 98%. The catalytic activities evaluated as turnover number (TON) values on the basis of metathesis products are higher than those in the CM reactions of MO with cis-4-octene (CO), cis-1,4-diacetoxy-2-butene (DAB), and allyltrimethylsilane (ATMS) reported previously (conducted under similar conditions);[41],b the selectivity of CM products (defined as select.(2)) is close to those in the CM reactions with ATMS, CO, and DAB.[41] It also turned out that the CM reaction of MO with UG proceeded without solvent (Table , run 5), although the conversion of MO was rather low.c These facts thus clearly indicate that the CM can be performed in environmentally friendly solvents (such as DMC, 2-propanol, and ethanol) without decreasing the catalyst efficiency.

On basis of the above results, DMC, 2-propanol, and ethanol were chosen for optimization of the reaction conditions (at 50 °C, the same catalyst loading, reaction time in Table ). Note that no significant changes in both MO conversion and selectivity of CM products (defined as select.(1)) were observed upon increasing the MO concentration (runs 7–10).b In contrast, both MO conversion and selectivity in DMC (run 6) decreased upon increasing the MO concentration. The CM reaction conducted in ethanol under high MO concentration (10 or 20 M), which was similar to that in 2-propanol with 4.0 M in terms of both MO conversion and selectivity (runs 8, 9 vs 10), seems to be thus appropriate for further study.

As shown in Table , the MO conversion in the CM slightly increased over time course (runs 8, 13, 14), and the conversion reached 96% after 30 min (from 91% after 10 min).b However, a longer reaction time led to an increase in the percentage of the SM product of UG (SM4, from 4 to 12%) as well as the degree of isomerization (UG to isoeugenol) in the reaction mixture (observed on the GC chromatogram, Figure S7 and Table S8, SI),a as reported previously.[41] Hence, extension of the reaction time (after 10 min) is not beneficial under these conditions.

Table 2

Cross-Metathesis (CM) of Methyl Oleate (MO) with Eugenol (UG) by G2.a,b

					metathesis products (%)e
run	UG (equiv)c	temp. (°C)	time (min)	MO conv.d (%)	CM1	CM2	CM3	CM4	SM1 trans	SM1 cis	SM2 trans	SM2 cis	select.(1)f (%)	select.(2)g (%)	TONh
13	10	50	5	72	31	36	17	18	1	0	1	0	72	98	520
8	10	50	10	91	31	48	17	21	1	0	1	0	65	98	590
14	10	50	30	96	44	60	15	17	1	0	1	0	72	98	690
15	1.0	50	10	92	34	29	13	21	4	1	8	3	61	86	560
16	5.0	50	10	95	33	44	14	19	1	0	2	0	60	97	570
17	20	50	10	81	28	39	13	10	1	0	0	0	56	99	450
18	10	25	10	48	15	20	10	9	1	0	0	0	56	98	270
19	10	80	10	91	35	47	14	11	1	0	1	0	61	98	560

Effect of UG/MO molar ratio, reaction time, and temperature.

Conditions: 2.00 mmol of MO, solvent ethanol, MO concentration 10.0 M, catalyst (G2) 0.002 mmol (0.1 mol %).

Based on MO.

Conversion of MO estimated by GC using an internal standard.

GC yield estimated according to the effect of carbon number (ECN) rule.

Selectivity of CM1–4 and SM1,2 based on the conversion of MO.

Selectivity of CM products (%) = (CM1 + CM2 + CM3 + CM4)/(CM1 + CM2 + CM3 + CM4 + SM1 + SM2). CM1: dec-1-ene, CM2: methyl dec-9-enoate, CM3: 2-methoxy-4-(undec-2-en-1-yl)phenol, CM4: methyl 11-(4-hydroxy-3-methoxyphenyl)undec-9-noate, SM1: octadec-9-ene, SM2: dimethyl octadec-9-enedioate.

TON = molar amount of metathesis product from MO (on the basis of MO conv. and select.(1))/Ru (mol). Detailed analysis data are shown in the SI.a

Moreover, it turned out that the UG/MO molar ratio (10 equiv of UG to MO) plays an important role in obtaining the CM products with high selectivity (defined as select.(2), runs 8, 15–17), whereas high MO conversion could be attained even with 1 equiv of UG (run 15). The high UG/MO ratio is crucial due to the low reactivity of UG, and this would be mostly considered in ordinary CM (with terminal olefins) of this type.[4−11,41] Consistently, formation of the SM products was considerably reduced at a high UG/MO molar ratio,a thereby confirming that the SM of MO was inhibited upon increasing the UG concentration. Further UG addition led to a decrease in the MO conversion (20 equiv, run 17), probably due to the increased degree of isomerization of UG observed on the GC chromatogram (Figure S8, SI).a

It also turned out that the reaction temperature affected both reaction rate and selectivity in this catalysis. The MO conversion at 50 °C reached 90% with exclusive CM selectivity (>98%, defined as select.(2), run 8), but the MO conversion was low at room temperature (25 °C, run 18). No significant improvements in both MO conversion and CM selectivity were, however, observed at 80 °C, and the degree of isomerization of UG increased instead (ca. 5 times compared to that at 50 °C, on the basis of the GC chromatogram, Figure S9 and Table S9, SI).a Isomerization of terminal olefin (to internal olefin) is often observed in olefin metathesis in the presence of ruthenium catalysts,[4−11,58−61] probably due to catalyst decomposition. These results revealed that the CM at 50 °C seems to be thus the appropriate condition in this catalysis.

Table summarizes CM of MO with UG in the presence of various ruthenium-carbene catalysts (shown in Scheme ) under the optimized conditions (conducted as run 8, in ethanol at 50 °C). Catalyst G2 (called a second-generation Grubbs catalyst) showed exceptionally better performance and higher MO conversion in the CM than G1 and G3 (runs 21, 22). The reason for the observed low activity by G1 would be due to catalyst decomposition because G1 is known to react with ethanol to form Ru-hydride species Ru(H)(Cl)(CO)(PCy3)2,[62] which is active in olefin isomerization catalysis. Indeed, the reaction with G1 led to the isomerization of UG predominantly (10%, Figure S10, SI).a Moreover, the conversion of MO and selectivity of CM and SM products (defined as select.(1)) by HG2 was lower than those by G2 (Table , runs 8, 23). An apparent increase in the activity (TONs on the basis of Ru) was not observed when the CM by G2 was conducted at low catalyst loading (from 0.1 to 0.05 mol %, runs 8, 20); moreover, an apparent decrease in the selectivity was not observed under these conditions.

Table 3

Cross-Metathesis of Methyl Oleate (MO) with Eugenol (UG)a,b

				metathesis products (%)e
run	catalyst (mol %)	UG (equiv)c	MO conv.d (%)	CM1	CM2	CM3		SM1 trans	SM1 cis	SM2 trans	SM2 cis	select.(1)f (%)	select.(2)g (%)	TONh
20	G2 (0.05)	10	58	20	26	12	12	1	0	0	0	62	98	720
8	G2 (0.1)	10	91	31	48	17	21	1	0	1	0	65	98	590
21	G1 (0.1)	10	8	1	1	1	1	0	0	0	0	28	84	22
22	G3 (0.1)	10	16	3	4	2	2	0	0	0	0	31	93	50
23	HG2 (0.1)	10	32	12	14	5	2	1	0	1	0	53	96	170

Effect of catalyst loading and different types of Ru-carbene catalysts.

Conditions: 2.00 mmol of MO, MO concentration 10.0 M, temperature 50 °C, reaction time 10 min.

Based on MO.

Conversion of MO estimated by GC using an internal standard.

GC yield estimated according to the effect of carbon number (ECN) rule.

Selectivity of CM1–4 and SM1,2 based on the conversion of MO.

Selectivity of CM products (%) = (CM1 + CM2 + CM3 + CM4)/(CM1 + CM2 + CM3 + CM4 + SM1 + SM2). CM1: dec-1-ene, CM2: methyl dec-9-enoate, CM3: 2-methoxy-4-(undec-2-en-1-yl)phenol, CM4: methyl 11-(4-hydroxy-3-methoxyphenyl)undec-9-noate, SM1: octadec-9-ene, SM2: dimethyl octadec-9-enedioate.

TON = molar amount of metathesis product from MO (on the basis of MO conv. and select.(1))/Ru (mol). Detailed analysis data are shown in the SI.a

In summary, CM of MO with UG has been performed with both high MO conversion and high selectivity of CM products using the G2 catalyst in ethanol (green solvent). Effects of the UG/MO molar ratio, reaction temperature (50 °C), initial MO concentration and others (catalyst, time etc.) play a role in obtaining the desired product in an efficient manner.

Cross-Metathesis (CM) of Various Methyl Esters (Methyl Petroselinate (MP), Methylerucate (ME), and Methyl 10-undecanoate (MU)) with Eugenol (UG)

On the basis of the above results from the CM of MO with UG, CM of the other unsaturated fatty acid methyl esters such as MP, ME, and MU with UG was conducted in ethanol in the presence of G2 (Scheme , conditions: Ru 0.1 mol % at 50 °C for 10 min, UG/substrate = 10 (molar ratio)). The selected results are summarized in Table .a As shown in Scheme (as well as explained in Scheme ), the CM of internal olefins (MP and ME) affords 4 types of CM products (expressed as CM1, CM2, CM3, and CM4), in addition to SM products. CM of MU with UG should afford one CM product (expressed as CM1).a

Scheme 3

Cross-Metathesis (CM) of Various Methyl Esters (Methyl Petroselinate (MP), Methylerucate (ME), and Methyl 10-undecanoate (MU)) with Eugenol (UG)

Table 4

Cross-Metathesis (CM) of Methyl Esters (MP, ME, and MU) with Eugenol (UG) by G2a

					metathesis products (%)d
run	substrate	UG (equiv)b	cat. (mol %)	conv.c (%)	CM1	CM2	CM3	CM4	SM1 trans	SM1 cis	SM2 trans	SM2 cis	select.(1)e (%)	select.(2)f (%)	TONg
24	MP	10	0.1	93	80	74	18	24	2	0	0	2	>99	98	920
25	ME	10	0.1	55	30	29	19	0	0	0	0	0	71	99	390
26	ME	10	0.2	95	78	70	8	0	1	0	0	0	83	99	390
27	MU	10	0.1	0	0	N/A	N/A	N/A	0	0	N/A	N/A	0	0	0
28	MU	5.0	0.5	47	4	N/A	N/A	N/A	2	0	N/A	N/A	7	67	7
29	MU	1.0	1.0	83	18	N/A	N/A	N/A	10	0	N/A	N/A	17	65	14

Conditions: 2.00 mmol of substrates (MP, ME, MU), solvent ethanol, substrate concentration 10.0 M, catalyst (G2), temperature 50 °C, time 10 min.

Based on substrates.

Conversion of substrates estimated by GC using an internal standard.

GC yield estimated according to the effect of carbon number (ECN) rule.

Selectivity of CM1–4 and SM1,2 based on the conversion of substrates.

Selectivity of CM products (%) = (CM1 + CM2 + CM3 + CM4)/(CM1 + CM2 + CM3 + CM4 + SM1 + SM2). CM1: tridec-1-ene (from MP), dec-1-ene (from ME), methyl 12-(4-hydroxy-3-methoxyphenyl)dodec-10-enoate (from MU), CM2: methyl hept-6-enoate (from MP), methyl tetradec-13-enoate (from ME), CM3: 2-methoxy-4-(tetradec-2-en-1-yl)phenol (from MP), 2-methoxy-4-(undec-2-en-1-yl)phenol (from ME), CM4: methyl 8-(4-hydroxy-3-methoxyphenyl)oct-6-enoate (from MP), methyl 15-(4-hydroxy-3-methoxyphenyl)pentadec-13-enoate (from ME), SM1: tetracos-12-ene (from MP), octadec-9-ene (from ME), dimethyl icos-10-enedioate (from MU), SM2: dimethyl dodec-6-enedioate (from MP), dimethyl hexacos-13-enedioate (from ME). N/A: not applicable.

TON = molar amount of metathesis product from MO (on the basis of MO conv. and select.(1))/Ru (mol). Detailed analysis data are shown in the SI.a

It should be noted that the CM of MP with UG proceeded with both high activity (920 turnovers after 10 min, high MP conversion) and exclusive selectivity (>98%, defined as select.(2), run 24).d In contrast, the CM of ME with UG only reached 55% under the same conditions (run 25, 390 turnovers). However, high ME conversion (95%), maintaining the exclusive selectivity of CM product (>99%, defined as select.(2)), could be achieved upon increasing G2 loading (0.2 mol %, run 26), although the percentage of one CM product (defined CM3), however, decreased upon increasing the catalyst loading probably due to the second metathesis. These results clearly indicate that these CM reactions (of MO, MP, and ME) with UG can be achieved in ethanol in an efficient manner in the presence of G2.

In contrast, unfortunately, attempted CM of MU (terminal olefins) with UG, conducted under the same conditions as those in the CM of MO (UG/MU = 10, molar ratio), afforded negligible MU conversion (run 27). Further attempts conducted under different MU/UG molar ratios with high G2 loading improved the MU conversion (up to 83%, run 29), but the yields of the desired CM products were very low (runs 28, 29), probably due to the subsequent isomerization of MU in situ leading to other metathesis reactions. In fact, the formation of the isomerized product of MU (methyl undec-9-enoate) and methyl 11-(4-hydroxy-3-methoxyphenyl)undec-9-enoate (CM1′), which should be formed by the subsequent CM with UG, in addition to dimethyl octadec-9-enedioate (SM1′) as the SM product was observed on the GC chromatogram (Scheme and Figures S15,S16, SI).a

Concluding Remarks

We have shown that CM reactions of renewable fatty acid methyl esters (MO, MP, and ME) with UG were successfully conducted by a ruthenium-carbene catalyst (G2, Scheme ) under environmentally benign conditions (in isopropanol or ethanol at 50 °C). The reaction conditions have been optimized to reach high substrate conversions with high CM selectivity, particularly for the CM of MO with UG. It turned out that both MO conversion and selectivity of CM products were highly affected by the initial MO concentration, UG/MO molar ratio, and reaction temperature. The catalyst performance was also affected by the substrate employed (in the order of MP > MO > ME); it thus seems likely that olefinic double bonds relatively close to the methyl ester showed better performance in the CM reaction with UG. It was also revealed that the subsequent isomerization of either UG or fatty acid methyl esters in situ significantly affects the CM and the SM product yields.

Experimental Section

All experiments were carried out under a nitrogen atmosphere unless otherwise specified. All chemicals used were of reagent grade and were purified by the standard purification procedures. Anhydrous grade dichloromethane (DCM, >99.5%) and n-hexane (Kanto Chemical Co., Inc.) were transferred into a bottle containing molecular sieves (mixture of 3A 1/16, 4A 1/8 and 13X 1/16) in a drybox. Ethanol dehydrated (>99.5%) and 2-propanol dehydrated (>99.7%) were supplied by Kanto Chemical Co., Inc. MO (>60%), MU (>96.0%), ME (methyl cis-13-docosenoate, >90.0%), MP (methyl cis-6-octadecenoate, >98.0%), UG (>99.0%), and DMC dehydrated (>98.0%) were obtained from Tokyo Chemical Industry, Co., Ltd. and were used as received. RuCl2(PCy3)2(CHPh) (G1, Cy = cyclohexyl), RuCl2(PCy3)(IMesH2)(CHPh) (G2, IMesH2 = 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene), RuCl2(IMesH2)(CH-2-OPr-C6H4) (HG2), and RuCl2(PCy3)(IMesH2)(CHPh)(3-BrC5H4N)2 (G3) were used in the drybox as received (Aldrich Chemical Co.). Methyl heptadecanoate (C17, GC standard, >99.0%), used as the internal standard (IS) for GC analyses, was also purchased from Aldrich.

Analytical GC characterization of mixtures was performed on GC-2025, Shimadzu, equipped with a DB-1 column (30 m × 0. 25 mm × 0.25 μm), using a flame ionization detector. Nitrogen gas was used as a carrier gas at a flow rate of 2.0 mL/min. The oven temperature program profile was as follows: column oven was kept at 50 °C for 10 min (initial temperature) and increased at 15 °C/min to 200 °C, and was held for 55 min (a total of 100 min for analyzing products of MU with UG). The quantitative analyses were performed by comparing the peak area of the products with a known amount of methyl heptadecanoate as an IS. The calibration coefficient was determined by analyzing the mixtures of substrates (MO, MP, ME, and MU) and the IS with different mass ratios. The amounts of substrates (MO, MP, ME, and MU) were thus calculated by normalizing using the internal standard method with the calibration coefficient. The conversion of substrates (MO, MP, ME, and MU) was estimated from the comparison of peak areas before and after the reactions. The effective carbon number (ECN) concept for GC-flame-ionization detector (FID) analyses was used to calculate the yields of products.[63−66] GC–MS analysis was carried out on a Shimadzu GC-17A gas chromatograph directly coupled to a mass spectrometer (MS) system of Shimadzu GCMS QP5050, equipped with a DB-1 column (30 m × 0.25 mm × 0.25 μm, with polyethylene glycol stationary phase). Helium gas was used as the carrier gas at a flow rate of 2.0 mL/min. The oven temperature program profile was the same as that employed for the ordinary GC analysis (a total of 100 min for analyzing products of MU with UG).

Thin layer chromatography (TLC) was carried out glass-backed silica plates, PLC Silica gel 60 F254, 0.5 mm (dimension 20 × 20 cm, Merck KGaA). The reaction products were identified by visualizing the plates under UV light (wavelength 254 nm). Silica gel column chromatography was carried out using dry silica (size 20–60 μm).

1H- and 13C NMR spectra were obtained by dissolving the samples in CDCl3 and recording the spectra using a Bruker AV500 NMR spectrometer (500.13 MHz for 1H and 125.77 MHz for 13C). All spectra were obtained in the solvent indicated at 25 °C unless otherwise noted. Chemical shifts (δ) were reported as ppm with tetramethylsilane as the IS (δ 0.00 ppm, 1H, 13C). The coupling constants are given in Hz. For 1H NMR and 13C NMR characterization, after solvent evaporation, the metathesis products of MO with UG were purified by column chromatography on silica gel (ethyl acetate/hexane mixtures) followed by thin layer chromatography (TLC, ethyl acetate/hexane mixtures).

Cross-Metathesis Reaction of Fatty Acid Methyl Esters (MO, MP, ME, and MU) with Eugenol

A typical procedure (Table , run 8) is as follows. The second-generation Grubbs catalyst, RuCl2(PCy3)(H2IMes)(CHPh) (G2, 1.7 mg, 0.1 mol %, 0.0020 mmol), was weighed in a 10 mL vial under a nitrogen atmosphere. Fatty acid methyl esters (MO (593 mg, 2.00 mmol), ME (706 mg, 2.00 mmol), MP (593 mg, 2.00 mmol), or MU (397 mg, 2.00 mmol)) and UG (3.284 g, 20.0 mmol, 10 equiv) were dissolved in solvent, and then quickly transferred to the catalyst vial. The mixture was stirred at 50 °C for 10 min, then the resulting mixture was passed through a packed column of Celite. Methyl heptadecanoate (10 mg) as an IS for GC analyses was added into the obtained filtrate. The mixture was then analyzed by using the gas chromatograph with the FID (GC-FID) and the gas chromatograph mass spectrometer (GC–MS). The GC-FID and GC–MS spectra are shown in the Supporting Information.

For characterization by the NMR spectra, the metathesis products of MO with UG were purified by column chromatography on silica gel (ethyl acetate/hexane mixtures) followed by thin layer chromatography (TLC, ethyl acetate/n-hexane = 2:8 v/v mixtures). Typical 1H NMR and 13C NMR spectra of CM products of MO with UG are shown in the Supporting Information.