In Situ-Generated Niobium-Catalyzed Synthesis of 3-Pyrroline Derivatives via Ring-Closing Metathesis Reactions.

An active in situ-generated Nb complex was used as a catalyst in the ring-closing metathesis reaction of N,N-diallyl-p-toluenesulfonamide to afford the corresponding 3-pyrroline derivative. The Nb complex was formed from NbCl5, trimethylsilyl chloride, Zn, and PhCHCl2 in tetrahydrofuran. The Nb complex displayed high catalytic activity toward ring-closing metathesis reactions.

Introduction

Olefin metathesis reactions are useful in organic syntheses. Ring-closing metathesis (RCM), in particular, is a powerful tool for the synthesis of numerous ring systems, including heterocyclic, polycyclic, medium-membered ring, and macrocyclic compounds from diolefins.[1] RCM has, therefore, been used in the synthesis of a wide-range of materials, such as drugs, functional materials, and natural products.[2] Generally, metathesis reactions are catalyzed by carbene complexes, such as the Schrock Mo-carbene complex (a)[3a] and the Grubbs Ru-carbene complexes (b and c)[3] (Scheme ). Research efforts with the aim of generating new and improved metathesis catalysts remain a significant interest. Likewise, studies of metathesis reactions catalyzed by early transition metals have been reported.[4a] Schrock reported a high oxidation state Ta and Nb-alkylidene complex (d) in the 1970s.[4]

Scheme 1

Various Carbene Complexes and Carbene Precursors

The Mashima group reported the development of metathesis catalysts based on Ta and Nb. The precatalysts e and f have been reported to show catalytic activity toward ring-opening metathesis polymerization (ROMP) of norbornene.[5a−5e] Nakayama et al. reported a system, in which an (aryloxy)tantalum or (aryloxy)niobium complex, in the presence of a trialkylaluminum co-catalyst, demonstrated catalytic activity in ROMP.[5] Galletti reported the ROMP reaction of norbornene catalyzed by niobium(V) N,N-dialkylcarbamates in the presence of methylaluminoxane.[5h] Recently, Veige et al. and Nomura et al. reported ROMP reactions catalyzed by a Nb-dineophyl complex with a [CF3-ONO]3 trianionic pincer-type ligand[5i] and the (imido)niobium-alkylidene complex Nb(CHSiMe3)(2,6-Me2C6H3N)[OC(CF3)3](PMe3)2,[5j] respectively. Bruno et al. used a niobium-imido complex as a catalyst for imine metathesis.[5k] However, synthesis of these catalysts requires multiple steps, including a thermally unstable step. Niobium-catalyzed RCM reactions have been less studied, and no examples have been reported.

RCM reactions catalyzed by the Tebbe reagent or Petasis reagent, which are titanium-based methylenation reagents, have been reported.[6a,6b] Takai reported the olefination of a carbonyl group using a titanium–zinc system, i.e., the Takai–Lombardo reaction (Scheme ).[6] This complex has also been employed as a precatalyst in RCM.[6g] However, elucidation of the structure of the active species is required.

Scheme 2

Olefination of Carbonyl Groups Using a Titanium-Based Complex

Niobium has multiple oxidation states, and numerous niobium complexes have been reported. Niobium catalysts have therefore received increasing attention in organic syntheses.[7] Our recent studies have demonstrated that niobium displays a high affinity for unsaturated bonds, such as olefin and alkyne bonds. In particular, low-valent niobium exhibits high catalytic activity toward cycloaddition reactions of alkynes with alkenes or nitriles.[7d−7i] High-valent niobium possesses strong Lewis acidity.[7j−7l]

In this study, Nb-based active species were generated in situ from niobium pentachloride. These materials catalyzed the RCM reactions of diallylic compounds quantitatively to yield various ring products. Additionally, the reactions proceeded via a one-step process.

Results and Discussion

The RCM of N,N-diallyl-p-toluenesulfonamide was initially investigated as a model substrate to optimize the reaction conditions (Table ). When a mixture of niobium pentachloride,[8] trimethylsilyl chloride (TMSCl), Zn, benzyl dichloride, and N,N-diallyl-p-toluenesulfonamide in tetrahydrofuran (THF) was heated at 60 °C for 2 h, the desired RCM product 1-(p-toluenesulfonyl)-3-pyrroline was isolated in 94% yield (Table , entry 1). The metathesis reaction also proceeded efficiently in the presence of NbCl4(THF)2 or NbCl3(DME) catalyst precursor (Table , entries 3 and 4). It was possible to reduce the amount of Zn when NbCl3(DME) was used (Table , entry 5). When substituting NbCl5 for Nb(OEt)5 catalyst, the RCM product yield was slightly lower, i.e., 91% (Table , entry 6). However, in the case of NbF5, the RCM product yield decreased significantly (Table , entry 7). Alternative metal chlorides, including TaCl5, TiCl4, and FeCl3, were also investigated; however, the desired RCM products were not obtained (Table , entries 8–10). The reaction did not proceed in the absence of a catalyst precursor (Table , entry 11). These results demonstrate that this catalytic transformation is specific for niobium-based catalysts. The reaction in the absence of TMSCl failed (Table , entry 12). In situ activation of zinc dust using TMSCl in THF has reported only a limited number of reactions,[9] such as the Reformatsky reaction.[9g]

Table 1

Optimization of Reaction Conditionsa

entry	catalyst precursor	additive	conv. (%)b	yield (%)b
1	NbCl5	PhCHCl2	>99	>99 (94)
2c	NbCl5	PhCHCl2	>99	>99
3	NbCl4(THF)2	PhCHCl2	>99	>99
4	NbCl3(DME)	PhCHCl2	>99	>99
5d	NbCl3(DME)	PhCHCl2	>99	>99
6	Nb(OEt)5	PhCHCl2	91	91
7	NbF5	PhCHCl2	14	5
8	TaCl5	PhCHCl2	9	nd
9	TiCl4	PhCHCl2	nr	nd
10	FeCl3	PhCHCl2	nr	nd
11	none	PhCHCl2	nr	nd
12e	NbCl5	PhCHCl2	nr	nd
13f	NbCl5	PhCHCl2	75	60
14g	NbCl5	PhCHCl2	1	trace
15h	NbCl5	PhCHCl2	nr	nd
16i	NbCl5	PhCHCl2	nr	nd
17j	NbCl5	PhCHCl2	nr	nd
18j	NbCl4(THF)2	PhCHCl2	nr	nd
19k	NbCl5	PhCHCl2	53	50
20l	NbCl5	PhCHCl2	56	4
21m	NbCl5	PhCHCl2	>99	>99
22n	NbCl5	PhCHCl2	>99	>99
23	NbCl5	PhCH2Cl	nr	nd
24	NbCl5	PhCCl3	nr	nd

Reaction conditions: 1a (1 mmol), catalyst (0.1 mmol), trimethylsilyl chloride (TMSCl, 0.5 mmol), Zn (1.5 mmol), additive (0.5 mmol), and THF (3 mL) at 60 °C for 2 h.

Conversions and yields were determined by gas chromatography (GC); the number in parentheses shows the isolated yield.

NbCl5 (5 mol %) was used.

Zn (1.0 mmol) was used.

In the absence of TMSCl.

Substituting 2-MeTHF for THF.

Substituting dioxane for THF.

Substituting tetrahydropyran (THP) for THF.

Substituting toulene for THF.

Substituting 1,2-dichloroethane (DCE) for THF.

Substituting Mn for Zn.

Substituting Mg for Zn.

Reaction temperature 40 °C.

At room temperature (ca. 22 °C).

Herein, the influence of solvents is also presented. When substituting THF for MeTHF, the desired RCM product was obtained, but in a lower yield, i.e., 60% (Table , entry 13). However, the use of dioxane afforded only trace quantities of the desired product (Table , entry 14).

Tetrahydropyran (THP), toluene, and 1,2-dichloroethane (DCE) are not suitable solvents, even in the presence of NbCl4(THF)2 (Table , entries 15–18). Notably, the replacement of Zn with Mn or Mg led to considerably decreased yields, which is attributed to a failure to form the organometallic compound and reduction of NbCl5 (Table , entries 19 and 20).

The investigations herein also examined the effects of reaction temperature. The reaction proceeded quantitatively at 40 °C and at room temperature (Table , entries 21 and 22). Furthermore, the reaction progress was examined at 60 °C to determine reproducibility.

When employing PhCH2Cl as a carbene precursor as a substitute to PhCHCl2, the reaction afforded 1,2-diphenylethane as a byproduct, with the desired RCM product not observed (Table , entry 23). Additionally, the use of PhCCl3 led to the formation of α,α′-dichlorostilbene and not the desired RCM product (Table , entry 24). When subjected to the model reaction conditions, stilbene formed as a dimer because of organozinc compound or a possible carbene complex formation during the reaction (vide infra, Scheme ). When TMSCl, Zn, THF, and PhCHCl2 were reacted at 60 °C for 2 h, stilbene was obtained in 66% yield (Scheme ), demonstrating that the organozinc compound dimerized yielding stilbene.[9c]

Scheme 6

Plausible Mechanism for the Formation of Nb-Based Active Species

Scheme 3

Generation of Stilbene in the Absence of NbCl5 and Trimethylsilyl Chloride

Substrate effect and limitations were examined using a variety of dienes under optimized conditions (Table ). First, the steric effects were investigated using N-allyl-N-(2-methylallyl)-p-toluenesulfonamide (1b), N,N-di(2-methylallyl)-p-toluenesulfonamide (1c), and N-allyl-N-(3-methyl-2-butenyl)-p-toluenesulfonamide (1d). When one side of the diene possessed bulky constituents, i.e., 1b and 1d, the corresponding pyrroline derivatives were obtained quantitatively. However, diene 1c, in which both sides are bulky, did not react (Table , entries 2–4). Additionally, 1e and 1f, differing in their carbon chain length, led to the corresponding six- or seven-membered ring, respectively, in moderate yields (Table , entries 5 and 6).

Table 2

Substrate Effect on Ring-Closing Metathesis (RCM) Reactionsa

Reaction conditions: diene (1 mmol), NbCl5 (0.1 mmol), TMSCl (0.5 mmol), Zn (1.5 mmol), PhCHCl2 (0.5 mmol), and THF (3 mL) at 60 °C for 2 h. Isolated yields.

No reaction.

40 °C for 6 h.

Selectivity determined by 1H NMR or 19F NMR.

Aniline derivatives were also examined. N,N-Diallylaniline (1g) reacted efficiently to give 2g in excellent yield. A small amount of the aromatized product, pyrrole 2g′, was also obtained. The reactions of the electron-rich anilines, N,N-diallyl-4-methylaniline (1h) and N,N-diallyl-4-methoxyaniline (1i), gave the corresponding products in high yields. Conversely, N,N-diallyl-4-trifluoroaniline (1j) was suitable, forming the corresponding product in excellent yield with high selectivity (Table , entries 7–10).

Benzyloxycarbonyl-protected diallylamine 1k was not suitable for this system. It is considered that the oxygen site inhibited the reaction (Table , entry 11). Furthermore, the malonate-based substrate 1l afforded a moderate amount of 2l (Table , entry 12).

The catalytic system in the cross-metathesis reaction having two different terminal olefins was also examined (Scheme ). 1-Dodecene (3a) (1 mmol) was reacted with vinylcyclohexane (3b) (10 mmol) to yield (22%) 1-cyclohexyl-1-dodecene (5ab) along with trace amounts of 11-docosene and dicyclohexylethene.

Scheme 4

Cross-Metathesis Study

The olefination reaction of ketone 4 was also examined (Scheme ). As a result, (cyclohexylidenemethyl)benzene (5c) was obtained in 20% yield. However, the product (5c) was not obtained in the absence of NbCl5, suggesting the formation of Nb-benzylidene species during the catalytic cycle.

Scheme 5

Olefination of Cyclohexanone Using the Present System

Although it is not possible to elucidate the detailed reaction mechanism, a possible reaction path for this transformation is shown in Scheme . First, a low-valent niobium species is generated by reduction of niobium chloride with Zn. The formation of an organozinc compound results from the reaction of PhCH2Cl2 with Zn and is activated by TMSCl. The low-valent Nb reacts with the organozinc compound to yield the Nb-based active species, and stilbene forms via dimerization of the organozinc compound.

The formation of Ru-carbene complexes by using PhCHCl2 was reported,[10] which suggests the formation of Nb-alkylidene analogues in our catalytic system. However, all of the attempts to isolate and characterize the Nb-alkylidene species were unsuccessful.

The subsequent carbene RCM reaction proceeds according to the general metathesis mechanism (Scheme ).[1j] The Nb-based active species A reacts with an olefin via B to give C, which reacts with another olefin via niobacycle D to yield the product, with regeneration of the active catalytic species A.

Scheme 7

Plausible Mechanism for the RCM Reaction

Conclusions

In summary, we have developed an in situ-generated Nb complex catalyst for the quantitative preparation of 3-pyrroline derivatives via the RCM reaction of N,N-diallyl-p-toluenesulfonamides. A series of RCM reactions with Nb as the catalyst was studied, and the desired products were obtained quantitatively. This study is one of only a few studies in this area, and the results will provide a platform for the development of other Nb-catalyzed metathesis reactions.

Experimental Section

General

GC analysis was performed with a flame ionization detector using a 0.22 mm × 25 m capillary column (BP-5). 1H and 13C NMR were measured at 400 and 100 MHz, respectively, in CDCl3 with Me4Si as the internal standard. Compounds 1a,[11]1b,[11]1c,[12]1d,[13]1e,[11]1f,[12]1g,[14]1h,[14]1i,[14]1j,[16]1k,[12]2a,[11]2b,[11]2e,[11]2f,[12]2g,[15]2g′,[14]2h,[18]2h′,[14]2i,[19]2i′,[14]2j,[20]2j′,[17] and 2l(12) are known compounds, which have previously been reported. Other compounds, including 1l, 3a, 3b, and NbCl5 (Wako, 95% purity), were purchased and used without purification.

Purification of Zinc (Wako, Powder, 75–150 μm)

Zn (5 g) was added to 10% HCl aq (20 mL) and stirred for 5 min. Thereafter, the mixture was filtered and washed with H2O (10 mL) and acetone (10 mL). The solid was dried under vacuum for 1 day.

Procedure for the Preparation of 2a (Entry 1, Table )

A mixture comprising THF (1.5 mL), Zn (98 mg, 1.5 mmol), and TMSCl (54 mg, 0.5 mmol) was stirred for 10 min at room temperature under an Ar atmosphere. Thereafter, PhCHCl2 (81 mg, 0.5 mmol) was added to the mixture and stirred for 10 min at 60 °C. At this time, a color change of the reaction mixture to grayish brown was observed. NbCl5 (27 mg, 0.1 mmol) in THF (1.5 mL) was added to the solution and stirred for 5 min, which resulted in the reaction mixture turning color from dark violet to dark brown. Finally, the substrate N,N-diallyl-p-toluenesulfonamide (1a, 251 mg, 1 mmol) was added to the solution and stirred for 2 h at 60 °C. The RCM product (2a) was isolated by column chromatography (silica gel (50 cc) neutralized by NEt3 (3 mL)/n-hexane/EtOAc = 100:0–4:1) in 94% yield (211 mg) as a white solid (mp 124–125 °C).

1a:[11] The product was prepared as follows: a mixture comprising N,N-diallylamine (27.5 mmol), TsCl (25 mmol), CH2Cl2 (100 mL), and triethylamine (40 mmol) was stirred for 16 h at room temperature. After the reaction, diethyl ether (100 mL) was added to the mixture, and the organic layer was washed with brine and concentrated under reduced pressure. Purification by silica gel chromatography (n-hexane/EtOAc = 8:1) gave 1a (22.9 mmol, 92%) as a colorless oil; 1H NMR (400 MHz; CDCl3) δ 2.43 (s, 3H), 3.80 (d, J = 6.4 Hz, 4H), 5.12–5.16 (m, 4H), 5.56–5.66 (m, 2H), 7.30 (d, J = 5.5 Hz, 2H), 7.71 (d, J = 5.3 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ 21.5 (CH3), 49.3 (CH2), 119.0 (CH2), 127.2 (CH), 129.7 (CH), 132.7 (CH), 137.4 (C), 143.2 (C); GC-MS (EI) m/z (relative intensity) 251 (7) [M+], 155 (49), 96 (58), 91 (100), 65 (27), 41 (51).

1b:[11] The product was prepared as follows: TsCl (12 mmol) in CH2Cl2 (20 mL) was added to a solution of N-allylamine (12.5 mmol) and triethylamine (12.5 mmol) in CH2Cl2 (20 mL) at 0 °C. The mixture was stirred at room temperature for 16 h. After the reaction, diethyl ether (50 mL) was added to the mixture, and the organic layer was washed with brine and concentrated under reduced pressure to afford N-allyl-p-toluenesulfonamide (11 mmol, 91%) as a white solid. Thereafter, a mixture composed of N-allyl-p-toluenesulfonamide (3 mmol), 1-bromo-2-methyl-2-propene (5 mmol), and Cs2CO3 (9 mmol) in CH3CN (35 mL) was stirred at 80 °C for 16 h. Thereafter, diethyl ether (50 mL) was added to the reaction mixture, and the organic layer was washed with brine and concentrated under reduced pressure. Purification by silica gel chromatography (n-hexane/EtOAc = 8:1) yielded 1b (2.6 mmol, 87%) as a colorless oil; 1H NMR (400 MHz; CDCl3) δ: 1.69 (s, 3H), 2.42 (s, 3H), 3.70 (s, 2H), 3.77 (d, J = 6.7 Hz, 2H), 4.85 (brs, 1H), 4.91 (brs, 1H), 5.06–5.08 (m, 1H), 5.10–5.11 (m, 1H), 5.47–5.57 (m, 1H), 7.29 (d, J = 7.9 Hz, 2H), 7.71 (d, J = 8.3 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 19.8 (CH3), 21.5 (CH3), 49.4 (CH2), 52.8 (CH2), 114.5 (CH2), 119.2 (CH2), 127.2 (CH), 129.6 (CH), 132.3 (CH), 137.4 (C), 140.1 (C), 143.2 (C); GC-MS (EI) m/z (relative intensity) 265 (9) [M+], 155 (77), 110 (33), 91 (100), 68 (27).

1c:[12] The product was prepared as follows: a mixture comprising p-toluenesulfonamide (3 mmol), 1-bromo-2-methyl-2-propene (9 mmol), and Cs2CO3 (9 mmol) in dimethylformamide (10 mL) was stirred at 50 °C for 24 h. Thereafter, diethyl ether (50 mL) was added to the mixture, and the organic layer was washed with brine and concentrated under reduced pressure. Purification by silica gel chromatography (n-hexane/EtOAc = 8:1) yielded 1c (2.9 mmol, 96%) as a colorless oil; 1H NMR (400 MHz; CDCl3) δ: 1.61 (s, 6H), 2.41 (s, 3H), 3.70 (s, 4H), 4.78 (brs, 2H), 4.86 (brs, 2H), 7.28 (d, J = 7.9 Hz, 2H), 7.71 (d, J = 8.1 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 19.9 (CH3), 21.4 (CH3), 53.0 (CH2), 114.4 (CH2), 127.1 (CH), 129.4 (CH), 137.3 (C), 140.0 (C), 143.0 (C); GC-MS (EI) m/z (relative intensity) 279 (10) [M+], 155 (72), 124 (33), 108 (21), 91 (100).

1d:[13] The procedure followed that of 1b except that 1-bromo-3-methyl-2-butene was used instead of 1-bromo-2-propene to afford 1d (2.9 mmol, 98%) as a yellow oil; 1H NMR (400 MHz; CDCl3) δ: 1.58 (s, 3H), 1.65 (d, J = 0.9 Hz, 3H), 2.42 (s, 3H), 3.78 (t, J = 5.8 Hz, 4H), 4.96–5.00 (m, 1H), 5.11 (t, J = 1.4 Hz, 1H), 5.14 (ddd, J = 7.9, 1.4, 0.7 Hz, 1H), 5.60–5.70 (m, 1H), 7.28 (d, J = 7.9 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H); 13C NMR (400 MHz; CDCl3) δ: 17.8 (CH3), 21.5 (CH3), 25.7 (CH3), 44.5 (CH2), 49.3 (CH2), 118.3 (CH2), 118.9 (CH), 127.2 (CH), 129.6 (CH), 133.3 (CH), 136.8 (C), 137.7 (C), 143.0 (C); GC-MS (EI) m/z (relative intensity) 279 (1) [M+], 155 (42), 124 (95), 68 (69), 41 (100).

1e:[11] The procedure was the same as for the preparation of 1b except that 1-bromo-3-butene substituted 1-bromo-2-propene to afford 1e (2.8 mmol, 93%) as a colorless oil; 1H NMR (400 MHz; CDCl3) δ: 2.27 (q, J = 7.3 Hz, 2H), 2.42 (s, 3H), 3.18 (t, J = 7.8 Hz, 2H), 3.81 (d, J = 6.4 Hz, 2H), 5.00–5.20 (m, 4H), 5.59–5.75 (m, 2H), 7.30 (d, J = 8.2 Hz, 2H), 7.70 (d, J = 8.2 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 21.5 (CH3), 32.9 (CH2), 46.7 (CH2), 50.7 (CH2), 117.0 (CH2), 118.8 (CH2), 127.1 (CH), 129.7 (CH), 133.2 (CH), 134.7 (CH), 137.1 (C), 143.2 (C); GC-MS (EI) m/z (relative intensity) 265 (1) [M+], 224 (92), 155 (78), 91 (100), 68 (33).

1f:[12] The procedure was the same as for the preparation of 1c except that 1-bromo-3-butene was used instead of 1-bromo-2-methyl-2-propene to afford 1f (2.7 mmol, 90%) as a colorless oil; 1H NMR (400 MHz; CDCl3) δ: 2.30 (q, J = 7.4 Hz, 4H), 2.42 (s, 3H), 3.19 (t, J = 7.7 Hz, 4H), 5.02–5.08 (m, 4H), 5.67–5.77 (m, 2H), 7.30 (d, J = 8.2 Hz, 2H), 7.70 (d, J = 8.2 Hz, 2H); 13C NMR (400 MHz; CDCl3) δ: 21.5 (CH3), 33.2 (CH2), 47.7 (CH2), 117.1 (CH2), 127.1 (CH), 129.6 (CH), 134.6 (CH), 136.9 (C), 143.1 (C); GC-MS (EI) m/z (relative intensity) 279 (1) [M+], 238 (44), 184 (46), 155 (66), 91 (100).

1g:[14] The product was prepared as follows: allylbromide (10 mmol) was added to a solution composed of aniline (3 mmol) and Cs2CO3 (3.5 mmol) in EtOH/H2O (12 mL, 4:1), and the mixture was stirred under reflux conditions (ca. 80 °C) for 2 days. After the reaction, diethyl ether (50 mL) was added to the mixture, and the organic layer was washed with brine and concentrated under reduced pressure. Purification by silica gel chromatography (n-hexane/EtOAc = 4:1) gave 1g (2.8 mmol, 93%) as a pale yellow oil; 1H NMR (400 MHz; CDCl3) δ: 3.82 (d, J = 4.9 Hz, 4H), 5.09–5.12 (m, 4H), 5.75–5.81 (m, 2H), 6.63 (t, J = 7.9 Hz, 3H), 7.14 (t, J = 7.9 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 52.6 (CH2), 112.3 (CH), 115.8 (CH2), 116.3 (CH), 129.0 (CH), 134.0 (CH), 148.6 (C); GC-MS (EI) m/z (relative intensity) 173 (79) [M+], 146 (100), 130 (56), 104 (76), 77 (80).

1h:[14] The procedure followed that of 1g except that p-methylaniline was used instead of aniline to afford 1h (2.7 mmol, 90%) as a colorless oil; 1H NMR (400 MHz; CDCl3) δ: 2.23 (s, 3H), 3.88 (d, J = 5.0 Hz, 4H), 5.12–5.19 (m, 4H), 5.82–5.87 (m, 2H), 6.62 (d, J = 8.6 Hz, 2H), 7.01 (d, J = 8.2 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 20.2 (CH3), 52.9 (CH2), 112.6 (CH), 115.9 (CH2), 125.5 (C), 129.6 (CH), 134.2 (CH), 146.6 (C); GC-MS (EI) m/z (relative intensity) 187 (100) [M+], 160 (90), 144 (36), 118 (75), 91 (76).

1i:[14] The procedure followed that of 1g except that p-methoxyaniline was used instead of aniline to afford 1i (2.7 mmol, 90%) as a colorless oil; 1H NMR (400 MHz; CDCl3) δ: 3.74 (s, 3H), 3.85 (d, J = 5.0 Hz, 4H), 5.12–5.20 (m, 4H), 5.80–5.89 (m, 2H), 6.68 (d, J = 9.1 Hz, 2H), 6.80 (d, J = 9.1 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 53.6 (CH2), 55.8 (CH3), 114.4 (CH), 114.6 (CH), 116.1 (CH2), 134.5 (CH), 143.5 (C), 151.5 (C); GC-MS (EI) m/z (relative intensity) 203 (100) [M+], 176 (41), 135 (55), 91 (9), 77 (16).

1j:[16] The procedure followed the preparation of 1g except that p-trifluoromethylaniline substituted aniline to afford 1j (2.0 mmol, 67%) as a colorless oil; 1H NMR (400 MHz; CDCl3) δ: 3.94 (d, J = 4.7 Hz, 4H), 5.14–5.17 (m, 4H), 5.80–5.83 (m, 2H), 6.67 (d, J = 8.9 Hz, 2H), 7.40 (d, J = 8.9 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 52.7 (CH2), 111.3 (CH), 116.3 (CH2), 117.7 (q, 2JC–F = 32.7 Hz, C), 125.2 (q, 1JC–F = 269 Hz, CF3), 126.4 (q, 3JC–F = 4.0 Hz, CH) 132.9 (CH), 150.8 (C); GC-MS (EI) m/z (relative intensity) 241 (84) [M+], 214 (79), 172 (36), 145 (51), 41 (100).

1k:[12] The product was prepared as follows: a solution of CbzCl (6.0 mmol) in DCE (10 mL) was added dropwise to a mixture comprising diallylamine (5.8 mmol) and triethylamine (6 mmol) in DCM (10 mL) and stirred for 20 min at room temperature. Thereafter, diethyl ether (50 mL) was added to the mixture, and the organic layer was washed with brine and concentrated under reduced pressure. Purification by silica gel chromatography (n-hexane/EtOAc = 3:1) yielded 1k (5.6 mmol, 97%) as a yellow oil; 1H NMR (400 MHz; CDCl3) δ: 3.88 (d, J = 12.6 Hz, 4H), 5.10–5.13 (m, 6H), 5.76 (brs, 2H), 7.34–7.35 (m, 5H); 13C NMR (100 MHz; CDCl3) δ: 48.8 (CH2), 49.1 (CH2), 67.1 (CH2), 116.9 (CH2), 117.1 (CH2), 127.7 (CH), 127.9 (CH), 128.4 (CH), 133.5 (C), 136.8 (CH), 155.9 (C); GC-MS (EI) m/z (relative intensity) 231(1) [M+], 140 (15), 114 (13), 91 (100), 65 (11).

2a:[11] yield 94% (211 mg), white solid (mp 124–125 °C) (lit.[11] 123.2–126.5 °C); 1H NMR (400 MHz; CDCl3) δ 2.43 (s, 3H), 4.12 (s, 4H), 5.65 (s, 2H), 7.32 (d, J = 8 Hz, 2H), 7.72 (d, J = 8 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ 21.5 (CH3), 54.8 (CH2), 125.5 (CH), 127.4 (CH), 129.8 (CH), 134.3 (C), 143.4 (C); GC-MS (EI) m/z (relative intensity) 223 (20) [M+], 155 (30), 91 (87), 77 (2), 68 (100), 63 (5).

2b:[11] yield 95% (225 mg), white solid (mp 98–99 °C) (lit.[11] 100.8–101.8 °C); 1H NMR (400 MHz; CDCl3) δ: 1.64 (s, 3H), 2.41 (s, 3H), 3.96 (s, 4H), 4.06 (s, 4H), 5.24–5.25 (m, 1H), 7.33 (d, J = 8.3 Hz, 2H), 7.72 (d, J = 8.3 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 14.0 (CH3), 21.5 (CH3), 55.1 (CH2), 57.7 (CH2), 119.1 (CH), 127.4 (CH), 129.8 (CH), 134.0 (C), 135.0 (C), 143.4 (C); GC-MS (EI) m/z (relative intensity) 237 (11) [M+], 222 (19), 91 (64), 82 (100), 65 (19).

2e:[11] yield 40% (95 mg) white solid (mp 94–95 °C) (lit.[11] 99.7–102.2 °C); 1H NMR (400 MHz; CDCl3) δ: 2.21 (s, 2H), 2.43 (s, 3H), 3.17 (t, J = 5.6 Hz, 2H), 3.57 (s, 2H), 5.61 (d, J = 9.5 Hz, 2H), 5.75 (d, J = 9.6 Hz, 2H), 7.32 (d, J = 7.7 Hz, 2H), 7.68 (d, J = 7.7 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 21.6 (CH3), 25.1 (CH2), 42.7 (CH2), 44.8 (CH2), 122.8 (CH), 125.0 (CH), 127.6 (CH), 129.6 (CH), 133.3 (C), 143.5 (C); GC-MS (EI) m/z (relative intensity) 237 (60) [M+], 155 (31), 91 (70), 82 (100), 55 (50).

2f:[12] yield 69% (173 mg), white solid (mp 60–63 °C); 1H NMR (400 MHz; CDCl3) δ: 2.32 (d, J = 4.5 Hz, 4H), 2.42 (s, 3H), 3.27 (t, J = 5.2 Hz, 4H), 5.75 (brs, 2H), 7.30 (d, J = 8.2 Hz, 2H), 7.67 (d, J = 8.2 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 21.5 (CH3), 29.9 (CH2), 48.3 (CH2), 116.1 (CH), 127.1 (CH), 129.7 (CH), 130.3 (CH), 136.2 (C), 143.1 (C); GC-MS (EI) m/z (relative intensity) 251 (13) [M+], 155 (7), 96 (27), 91 (26), 77 (2), 41 (100).

2g,[15]2g′:[14] yield 96% (96:4) (139 mg), white solid (mp 90–91 °C) (lit. 2g:[13] 101–102 °C, 2g′:[12] 56–60 °C)

1H NMR (400 MHz; CDCl3) δ: 4.08 (s, 4H), 5.93 (brs, 2H), 6.52 (d, J = 8.6 Hz, 2H), 6.68 (t, J = 7.3 Hz, 1H), 7.24 (t, J = 8.7 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 54.4 (CH2), 111.1 (CH), 115.5 (CH), 126.4 (CH), 129.3 (CH), 147.0 (C); GC-MS (EI) m/z (relative intensity) 145 (100) [M+], 127 (8), 104 (63), 91 (9), 77 (50).

1H NMR (400 MHz; CDCl3) δ: 6.34 (t, J = 2.2 Hz, 2H), 7.07 (t, J = 2.2 Hz, 2H), 7.10 (s, 1H), 7.2–7.5 (m, 4H); 13C NMR (100 MHz; CDCl3) δ: 110.4 (CH), 119.3 (CH), 120.5 (CH), 125.6 (CH), 129.5 (CH), 137.3 (C); GC-MS (EI) m/z (relative intensity) 143 (100) [M+], 115 (57), 104 (4), 77 (14).

2h,[18]2h′:[14] yield 75% (84:16) (119 mg), white solid (mp 88–90 °C) (lit. 2h:[18] 92–93 °C, 2h′:[14] 82.5–83.3 °C)

1H NMR (400 MHz; CDCl3) δ: 2.24 (s, 3H), 4.04 (s, 4H), 5.89 (s, 2H), 6.43 (d, J = 8.2 Hz, 2H), 7.04 (d, J = 8.3 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 20.2 (CH3), 54.5 (CH2), 111.1 (CH), 124.4 (C), 126.4 (CH), 129.7 (CH), 145.0 (C); GC-MS (EI) m/z (relative intensity) 159 (100) [M+], 143 (31), 118 (76), 91 (48), 77 (5).

1H NMR (400 MHz; CDCl3) δ: 2.33 (s, 3H), 6.31 (s, 2H), 7.03 (s, 2H), 7.17 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.1 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 20.8 (CH3), 110.0 (CH), 119.2 (CH), 120.4 (CH), 130.0 (CH), 135.2 (C), 138.4 (C); GC-MS (EI) m/z (relative intensity) 157 (100) [M+], 129 (26), 115 (21), 77 (5), 65 (10).

2i,[19]2i′:[14] yield 76% (82:18) (133 mg), white solid (mp 107–108 °C) (lit. 2i′:[14] 110–111 °C)

1H NMR (400 MHz; CDCl3) δ: 3.74 (s, 3H), 4.05 (s, 4H), 5.91 (s, 2H), 6.47 (d, J = 8.7 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 54.8 (CH3), 55.9 (CH2), 111.7 (CH), 115.1 (CH), 126.5 (CH), 142.1 (C), 150.7 (C); GC-MS (EI) m/z (relative intensity) 175 (100) [M+], 134 (62), 160 (35), 130 (17), 77 (18).

1H NMR (400 MHz; CDCl3) δ: 3.80 (s, 3H), 6.31 (s, 2H), 6.92 (d, J = 8.6 Hz, 2H), 6.98 (s, 2H), 7.28 (d, J = 8.6 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 55.4 (CH3), 109.8 (CH), 114.5 (CH), 119.6 (CH), 122.0 (CH), 134.4 (C), 157.6 (C); GC-MS (EI) m/z (relative intensity) 173 (88) [M+], 158 (100), 130 (43), 103 (16), 77 (12).

2j,[20]2j′:[17] yield 90% (97:3) (192 mg), white solid (mp 114–115 °C) (lit. 2j′:[17] 112–114 °C)

1H NMR (400 MHz; CDCl3) δ: 4.10 (s, 4H), 5.93 (t, J = 4.2 Hz, 2H), 6.49 (d, J = 8.6 Hz, 2H), 7.45 (d, J = 8.7 Hz, 2H); 13C NMR (100 MHz; CDCl3) δ: 54.3 (CH2), 110.5 (CH), 117.0 (q, 2JC–F = 32.6 Hz, C), 125.3 (q, 1JC–F = 270 Hz, CF3), 126.1 (CH), 126.5 (q, 3JC–F = 3.8 Hz, CH), 148.9 (C); GC-MS (EI) m/z (relative intensity) 213 (100) [M+], 194 (9), 172 (79), 145 (54), 115 (10).

GC-MS (EI) m/z (relative intensity) 211 (100) [M+], 192 (6), 164 (7), 145 (13), 115 (59).

2l:[12] yield 65% (138 mg), yellow oil; 1H NMR (400 MHz; CDCl3) δ: 1.25 (t, J = 7.1 Hz, 7H), 3.01 (s, 4H), 4.20 (dd, J = 7.1, 3.6 Hz, 4H), 5.58–5.63 (m, 2H); 13C NMR (100 MHz; CDCl3) δ: 14.0 (CH3), 40.8 (CH2), 58.8 (C), 61.5 (CH2), 127.8 (CH), 172.2 (C); GC-MS (EI) m/z (relative intensity) 212 (19) [M+], 79 (51), 66 (80), 55 (9), 29 (100).

5ab: A mixture composed of THF (1.5 mL), Zn (196 mg, 3.0 mmol), and TMSCl (108 mg, 1.0 mmol) was stirred for 10 min at room temperature under an Ar atmosphere. Thereafter, PhCHCl2 (162 mg, 1.0 mmol) was added to the mixture and stirred for 10 min at 60 °C. The mixture turned color slightly to grayish brown. NbCl5 (54 mg, 0.2 mmol) in THF (1.5 mL) was added to the solution and stirred for 5 min resulting in the mixture turning color from dark violet to dark brown. Finally, 1-dodecene (3a, 168 mg, 1 mmol) and the substrate vinylcyclohexane (3b, 1102 mg, 10 mmol) were added to the solution and stirred for 2 h at 60 °C. The yield of the metathesis product (5ab, 22%) was estimated from the peak areas based on an internal standard technique using GC and tridecane as the internal standard. The cross-metathesis product (5ab) was isolated (9% yield, 24 mg) by column chromatography (silica gel (25 cc)/n-hexane/EtOAc = 100:0–4:1) and Kugel-Rohr distillation (pot temperature 100–110 °C), as a colorless oil; 1H NMR (400 MHz; CDCl3) δ: 0.88 (t, J = 6.8 Hz, 3H), 1.32–1.02 (m, 21H), 1.72–1.61 (m, 5H), 1.97–1.93 (m, 3H), 5.35–5.33 (m, 2H); 13C NMR (100 MHz; CDCl3) δ: 14.1 (CH3), 22.7 (CH2), 26.1 (CH2), 26.2 (CH2), 29.1 (CH2), 29.4 (CH2), 29.5 (CH2), 29.64 (CH2), 29.65 (2CH2), 29.70 (CH2), 31.9 (CH2), 32.7 (CH2), 33.3 (2CH2), 40.7 (CH), 127.7 (CH), 136.4 (CH); IR (neat, cm–1) 2924, 1449, 967; GC-MS (EI) m/z (relative intensity) 250 (16) [M+], 109 (43), 96 (100), 81 (82), 67 (65); HRMS (EI) m/z calcd for C18H34 [M]+ 250.2661, found 250.2662.