Synthesis of Various Heterocycles Having a Dienamide Moiety by Ring-Closing Metathesis of Ene-ynamides

Abstract

Ring-closing metathesis (RCM) of ynamides, having alkene substituents of various lengths on the side chain, was demonstrated using the second-generation Grubbs catalyst. When the reaction of ene-ynamides was carried out in the presence of 5 mol% of the catalyst, RCM proceeded smoothly to give quinoline or isoquinoline derivatives having a dienamide unit in good yields. Furthermore, RCM of ene-ynamides, having one more carbon on the side chain, proceeded smoothly to provide seven-membered heterocycles having a dienamide component. Similarly, eight-membered heterocycles, diazocine and benzodiazocine, were also synthesized by RCM of ene-ynamides in good yields.

Key words

ruthenium carbene complex - ynamide - ring-closing metathesis - heterocycles - medium-sized ring

Carbon–carbon double bonds have been shown to be useful building blocks in synthetic organic chemistry.[1] Olefin metathesis, which is catalyzed by transition metal complexes, is one of the most powerful tools for the construction of the C=C bonds.[2] Ring-closing metathesis (RCM) is used as a key reaction for the synthesis of various natural products, and is the essential method for the construction of the carbon framework at this moment. Likewise, ring-closing enyne metathesis (RCEYM) has attracted much interest because various cyclic products having a conjugated diene moiety can be obtained in a single step.[3] The distinctive reactivity of ynamides, which have an electron-deficient π-orbital and higher stability relative to ynamines, is attractive for organic chemists.[4] As useful synthetic methods for the preparation of ynamides have already been reported by Kitamura,[5] Brückner[4i] [6] and Hsung,[7] a variety of ynamides can be synthesized at present.

Several kinds of transition-metal-catalyzed reactions of ynamides, including [2+2+1] cycloaddition,[8g] Pauson–Khand reaction,[8h] cycloisomerization,[8i] triazole synthesis,[8j] [4+2] cycloaddition,[8k] [2+2] cycloaddition,[8l] and Sonogashira cross-coupling,[8m] [n] have been reported in recent years.[8] We have studied RCM of ene-ynamides, which can be applied for the synthesis of pyrrolizidine and piperidine derivatives. Furthermore, the diene derivative, which was obtained by RCM of ene-ynamide, can afford indole and quinoline derivatives by Diels–Alder reaction (Scheme [1]).[9]

Scheme 1 Synthesis of pyrrolidine and piperidine derivatives using RCM of ene-ynamide

On the basis of the above discussion, we decided to explore the further expansion of the RCM of ene-ynamides. Herein, we wish to report the synthesis of various heterocyclic compounds having a dienamide moiety, especially to establish the efficient synthesis of seven- and eight-membered heterocycles.[10] Ene-ynamide derivatives were prepared by the several synthetic methods, as shown in Schemes 2 through 5.

Tosyl amides 2–4, which were synthesized by the literature procedure,[11] [12] [13] were treated with butyllithium, followed by treatment with formylbenzotriazole, to provide N-formyl derivatives 5–7. The ynamide unit was constructed by the modified Corey–Fuchs alkyne synthesis[6] [14] to obtain ene-ynamides 11–13. Ene-ynamide 12c, having a phenyl group on the alkyne, was obtained from compound 9 by Negishi coupling (Scheme [2]).[15]

Scheme 2 Preparation of substrate for the synthesis of quinoline, isoquinoline, and benzazepine derivatives

Mitsunobu reaction[16] of 14 and 15, followed by dichloro­olefination, provided 16, which could be converted into 17 in good yield by treatment with butyllithium (Scheme [3]).

Scheme 3 Preparation of substrate for the synthesis of azepine derivative

Allyl tosyl amide 19, whose synthesis was reported by Stetter,[17] was reacted with butyllithium and iodonium salt 20 to provide 21d in 61% yield. Ene-ynamide 21a was obtained from 21d by the removal of the TMS group on the alkyne. The synthesis of ene-ynamide 21b and 21c from 21a was accomplished by lithiation on the terminal alkyne or Sonogashira cross-coupling[18] (Scheme [4]).

Scheme 4 Preparation of substrate for the synthesis of benzodiazepine derivatives

Alcohols 24 and 25 were prepared from 22 [19] by the easy exchange of its protecting group. Mitsunobu reaction of N-tosylformamide 14 and alcohol 23–25, followed by treatment with carbon tetrachloride and triphenylphosphine, provided dichloroolefins 26–28, which were treated with butyllithium and ammonium chloride or ethyl chlorocarbonate to obtain ene-ynamides 29–31 in good yields (Scheme [5]).

Scheme 5 Preparation of substrate for the synthesis of azocine derivatives

The synthetic route for the preparation of compounds 46 and 47 is shown in Scheme [5]. N-Boc-protected tosylamide derivative 36 was obtained through a stepwise Mitsunobu reaction of propanediol derivative 33 with allyl tosyl amide 32 and N-Boc tosylamide 35, in good yield. On the other hand, the synthesis of an another N-Boc tosylamide derivative 39 having a phenyl group on the alkyl chain was accomplished by Mitsunobu reaction of 38, which was synthesized by a literature procedure.[20] N-Boc deprotection of the compounds 36 and 39 by treatment with trifluoroacetic acid afforded tosylamide derivatives 40 and 41, which upon formylation, dichloroolefination, and alkynylation provided ene-ynamides 46a, 46b, and 47a, 47b, respectively. TMS-protected ene-ynamide 47c, on the other hand, was obtained by the reaction of tosylamide 41 with butyllithium and iodonium salt 20.

The synthesis of quinoline derivative 48 is shown in Table [1]. The reaction of 11a in the presence of 5 mol% of the second-generation Grubbs catalyst 1b in toluene at 80 °C for 0.5 hour under ethylene atmosphere furnished quinoline derivative 48a in 93% yield (Table [1], entry 1). The reaction of ene-ynamide having an ethoxycarbonyl group on the alkyne did not give good results (entry 2). However, this problem was solved by replacing ethylene by argon, leading to the formation of the cyclized product 48b in 79% yield (entry 3).

Table 1 Construction of Quinoline Ring

Entry	Substrate	Atmosphere	Time (h)	48	Yield (%)
1	11a	CH2=CH2	0.5	48a	93
2	11b	CH2=CH2	12	48b	49a
3	11b	Ar	1	48b	79

^a Starting material 11b was recovered in 11% yield.

Next, Diels–Alder reaction of 48a with dimethyl acetylenedicarboxylate (DMAD) was examined. It was found that the construction of acridine skeleton was possible, and compound 49 was obtained in 45% yield (Scheme [6]).

Scheme 6 Synthesis of acridine derivative by Diels–Alder reaction of cyclic dienamides

The synthesis of isoquinoline derivatives was examined as further application of the construction of 6+6 ring system. The reaction of ene-ynamide 12a with 5 mol% of catalyst 1b under an identical reaction conditions proceeded smoothly to furnish the cyclized product 50a in 70% yield, in only 30 minutes (Table [2], entry 1). Substituted alkynes can be used in this isoquinoline synthesis, in contrast to the quinolone synthesis. The cyclized product 50b was obtained in 78% yield, when the ethoxycarbonyl group was substituted on the alkyne (entry 2). Although a slightly longer reaction time was required in the case of the phenyl-substituted alkyne, the resulting isoquinoline derivative 50c was obtained in almost identical yield (entry 3).

Table 2 Construction of Isoquinoline Ring

Entry	Substrate	Time (h)	50	Yield (%)
1	12a	0.5	50a	70
2	12b	1	50b	78
3	12c	1.5	50c	77

When a toluene solution of 50a and DMAD was stirred at 80 °C for 21 hours, the Diels–Alder reaction proceeded smoothly to provide phenanthridine derivative 51 in 50% yield. However, the double bond of 51 was isomerized to a conjugated position, which was different from the expected position. On the other hand, tricyclic compound 52 was obtained without isomerization of the double bond when the metathesis reaction of 12a was carried out under identical conditions, followed by the treatment with DMAD under argon atmosphere (Scheme [7]).[21] It is not clear at this stage why the double bond of 52 is not isomerized to a conjugated position. If the lone pair of nitrogen or π electrons is associated to ruthenium center, the double bond isomerization is suppressed.

Scheme 7 Synthesis of phenanthridine derivatives

Table 3 Construction of Benzazepine Ring

Entry	Substrate	Atmosphere	1b (mol%)	Time (h)	53	Yield (%)a
1	13a	CH2=CH2	10	1.5	53a	22
2	13a	Ar	5	0.5	53a	49
3	13b	CH2=CH2	10	3.5	53b	69
4	13b	Ar	5	0.5	53b	84

^a Isolated yield.

The construction of a benzazepine ring was examined next. When a toluene solution of 13a was stirred with 10 mol% of the catalysts 1b at 80 °C for 1.5 hours under an ethylene atmosphere, the cyclized product 53a was obtained in 22% yield (Table [3], entry 1). A corresponding reaction carried out under an argon atmosphere led to an improved yield of 53a at 49% (entry 2). RCM of 13b, which was prepared by the introduction of an ethoxycarbonyl group on the alkyne, was attempted next. When the reaction of 13b was carried out in a manner similar as that used for the synthesis of 53a, benzazepine derivative 53b was obtained in 69% yield (entry 3). This yield could be enhanced to 84% by performing the reaction under an argon atmosphere (entry 4).

Furthermore, the synthesis of 54 was examined with the aim of constructing the dibenzoazepine skeleton (Scheme [8]). Tricyclic heterocycle 54 was obtained in 36% yield when 13a was exposed to a catalytic amount of 1b in toluene at 80 °C for 0.5 hour under argon atmosphere, followed by treatment with DMAD at the same temperature.

Scheme 8 Synthesis of dibenzoazepine derivative

Next, RCM of linear α,ω-ene-ynamides was examined. When the reaction of 17a was carried out in the presence of the catalyst 1b in toluene at 80 °C for 1 hour, starting material 17a was recovered in 53% yield (Table [4], entry 1). Replacement of toluene by CH₂Cl₂ led to a better result, and 55a was obtained in 36% yield after heating for 15 hours, together with 38% of 17a (entry 2). A similar result was achieved when the reaction was conducted under an argon atmosphere or upon prolonging the reaction time (entries 3 and 4). In the case of 17b, a substrate having an ethoxycarbonyl group on the alkyne, the yield of the cyclized product 55b was only 5% when the reaction was carried out in toluene with heating (entry 5). However, a higher yield of 55b was obtained when the reaction was carried out in CH₂Cl₂ (entry 6).

Table 4 Construction of Azepine Ring

Entry	Substrate	Atmosphere	Time (h)	55	Yield (%)a	17	Recovery of 17 (%)a
1b	17a	CH2=CH2	1	–	–	17a	53
2	17a	CH2=CH2	15	55a	36	17a	38
3	17a	Ar	26	55a	37	17a	33
4	17a	Ar	48	55a	33	17a	31
5b	17b	CH2=CH2	3	55b	5	17b	74
6	17b	CH2=CH2	1.5	55b	74c	17b	–

^a Yields were determined by ¹H NMR spectroscopy using (E)-stilbene as an internal standard.

^b Reaction was carried out in the presence of 5 mol% 1b in toluene at 80 °C.

^c Isolated yield.

Subsequently, the synthesis of 1,5-benzodiazepine derivatives was also examined. When a solution of 21a in toluene­ was exposed to a catalytic amount of 1b at 80 °C for 1 hour, the starting material 21a was not consumed, and an inseparable complex mixture consisting of 21a, cyclized product 56a, an intermolecular metathesis product with ethylene, and undefined products was obtained (Table [5], entry 1). Replacement of the solvent and a longer reaction time gave a similar result (entry 2). The reaction of the TMS-substituted ene-ynamide 21d did not proceed and the starting material was recovered (entry 3). Surprisingly, when 21b was used as the substrate instead of 21a, benzodiazepine 56b was obtained in quantitative yield (entry 4). Reduction of the catalyst amount did not affect the yield of 56b (entry 5). The RCM also proceeded smoothly in CH₂Cl₂ as the solvent, although a longer reaction time was required (entry 6). An excellent yield of 56b was also observed when the reaction was carried out under an argon atmosphere (entry 7). Likewise, when the phenyl-substituted ene-ynamide 21c was used as the substrate, benzodiazepine 56c was obtained in quantitative yield (entry 8).

Table 5 Construction of Benzodiazepine Ring

Entry	Substrate	Solvent	Temp (°C)	Time (h)	56	Yield (%)a
1	21a	toluene	80	1	–	–
2	21a	CH2=CH2	reflux	28	–	–
3	21d	toluene	80	5	–	–b
4	21b	toluene	80	0.5	56b	99
5c	21b	toluene	80	0.5	56b	99
6	21b	CH2Cl2	reflux	15	56b	97
7d	21b	CH2Cl2	reflux	20	56b	95
8	21c	toluene	80	1	56c	97

^a Isolated yield.

^b Recovered 21d: 87%.

^c Catalyst 1b used: 5 mol%.

^d Reaction was carried out under an argon atmosphere.

Encouraged by the successful construction of the six-membered rings and a seven-membered ring, we became interested in the synthesis of eight-membered heterocycles. Initially, various linear ene-ynamides were examined for the synthesis of azocine derivative 57. However, the desired cyclized product 57 was not obtained in any case, and the only a trace amount of alkene dimer, formed by the intermolecular reaction of the ene-ynamides was observed in NMR experiment (Scheme [9]).

Scheme 9 Construction of azocine ring

Furthermore, RCM of linear ene-ynamide 46, which contains two tosylamide groups in the chain, was examined. When a CH₂Cl₂ solution of 46a was heated for 21 hours in the presence of 10 mol% of 1b, starting material 46a was recovered in 33% yield (Table [6], entry 1). The introduction of an ethoxycarbonyl group on the alkyne promoted the formation of an eight-membered ring, and diazocine 58b was obtained in 15% yield (entry 2). Improved yield was achieved when the reaction was performed under an argon atmosphere (entry 3). Higher recovery of starting material 46b was observed when toluene was used as the solvent (entry 4). However, an encouraging result was observed in the construction of an eight-membered ring, and 58b was obtained in 78% yield when the reaction was conducted under­ high-dilution conditions (entry 5).

Table 6 Construction of Diazocine Ring

Entry	Substrate	Atmosphere	Time (h)	58	Yield (%)a	46	Recovery of 46 (%)a
1	46a	CH2=CH2	21	–	–	46a	33
2	46b	CH2=CH2	21	58b	15	46b	49
3	46b	Ar	21	58b	33	46b	25
4b	46b	CH2=CH2	6	58b	–	46b	68
5c	46b	Ar	24	58b	78d	–	–

^a Yields were determined by ¹H NMR spectrum using (E)-stilbene as an internal­ standard.

^b Reaction was carried out in the presence of 5 mol% 1b in toluene at 80 °C.

^c Reaction was carried out under low concentration (0.002 M).

^d Isolated yield.

Next, the synthesis of benzodiazocine was examined. The reaction of 47a with the catalyst 1b did not proceed, and starting material was recovered (Table [7], entry 1); shortening of the reaction time did not affect the result (entry 2). Then, a solution of 47b in CH₂Cl₂ was heated in the presence of 1b for 21 hours, and the reaction was monitered by TLC (entry 3). A new spot appeared on the TLC plate, suggesting the formation of 59b. However, it was difficult to deduce the correct structure of 59b due to the broad peaks in its ¹H NMR spectrum. This was probably due to the rapid interconversion of several stable confomers under the influence of the benzene ring, at room temperature. The peaks were clearly separated when the ¹H NMR spectrum was recorded at low temperature of –50 °C (Figure [1]). We have reported that the dimeric compound was obtained, because the largest m/z value of FAB-MS spectra was observed at 1133 (M⁺ + H).[10] However, the structure of the metathesis product was conclusively established by X-ray crystallography (Figure [2]), and it was found that the desired eight-membered ring 59b was obtained in 14% yield.

Table 7 Construction of Benzodiazocine Ring

Entry	Substrate	Atmosphere	Time (h)	59	Yield (%)a	47	Recovery of 47 (%)a
1	47a	CH2=CH2	21	–	–	47a	58
2b	47a	CH2=CH2	0.5	–	–	47a	53
3	47b	CH2=CH2	21	59b	14	47b	63
4	47b	Ar	21	59b	52	47b	44
5b	47b	CH2=CH2	6	–	–	47b	86
6b	47b	Ar	2	59b	77	–	–
7b	47c	Ar	17	–	–	47c	83
8	47c	Ar	6	–	–	47c	99

^a Isolated yield.

^b Reactions were carried out in the presence of 5 mol% 1b in toluene at 80 °C.

Figure 1 ¹H NMR spectrum of 59b

Figure 2 X-ray crystal structure of 59b

An argon atmosphere was effective for the cyclization of 47b, and the yield of 59b was increased to 52% (Table [7], entry 4). Appropriate combination of the solvent and the atmosphere was important for the formation of 59b. Upon changing the solvent to toluene from CH₂Cl₂, high recovery of 47b was observed under an ethylene atmosphere (entry 5) and a higher yield of 59b was observed under an argon atmosphere (entry 6). Unfortunately, in the case of the phenyl-substituted ene-ynamide 47c, the formation of the eight-membered heterocycle 59c was not observed, and the starting material was recovered in high yield (entries 7, 8).

Furthermore, the effect of temperature on the construction of the eight-membered-ring compounds was examined (Table [8]). A lower reaction rate was observed with the decreasing reaction temperature, and 59b was obtained in 45% yield at room temperature with the recovery of the starting material 47b in 16% yield (entry 3).

Table 8 Temperature Effect for the Construction of Eight-Membered Ring

Entry	Temp (°C)	Time (h)	Yield of 59b (%)a	Recovery of 47b (%)a
1	80	2	77	–
2	50	10	57	4
3	r.t.	42	45	16

^a Isolated yield.

It is thought that this reaction progresses via one of the two pathways described in Scheme [10]. In the yne-then-ene pathway (cycle a), the carbene complex 1 first reacts with substrate A or ethylene to provide ruthenium carbene complex I, which is the active species for the metathesis reaction. Carbene complex I then reacts with the alkyne part of A to provide ruthenacyclobutene II, which is converted to complex III. If the ruthenium carbene part of III reacts with the alkene part intramolecularly, ruthenacyclobutane IV would be obtained, which then converts to product B, regenerating ruthenium carbene complex I. On the other hand, ruthenium carbene V is thought to be formed, when 1 reacts with the alkene part of A (cycle b, ene-then-yne pathway). The carbene part of complex V then reacts with the alkyne part of V intramolecularly to provide ruthenacyclobutene VI, which converts into complex VII. If the carbene part of VII reacts with A intermolecularly, the desired product B would be obtained together with V. Two intriguing results were observed in the construction of the seven- and eight-membered ring:

1) The desired product was obtained in high yield when substituents were present on the terminal alkyne, while the yield of the cyclized product was decreased in the case of unsubstituted ene-ynamides.

2) The reaction proceeded under an argon atmosphere to provide the cyclized product in a yield similar to that obtained under an ethylene atmosphere.

Scheme 10 Proposed reaction mechanism

The reactivity of the ruthenium complex with the C≡C bond should increase because of the higher electron density of ynamides. As a result, the yne-then-ene mechanism would predominate (cycle a). On the other hand, it is thought that the reaction of the ruthenium complex and the double bond have an advantage when a substituent exists on the terminal alkyne. The ruthenium carbene should react with the double bond instead of the triple bond, by the introduction of the ethoxycarbonyl group on the alkyne. These effects, which decrease the electron density of ynamides, would favor the predominance of the ene-then-yne mechanism (cycle b).

Taking into consideration the ring-closure factor, it is proposed that the rate of ring closure for medium-sized rings is lower than that for five- or six-membered rings. If the conversion rate from III to IV decreases, complex III would react with the substrate or the other alkene species to provide a variety of alkene compounds. On the other hand, if the conversion rate from V to VI decreases, complex V would react intermolecularly with the alkene part of an another substrate to form the alkene dimer. In addition, complex V would react only with ethylene in the case of the reaction of 47b under ethylene atmosphere.

It is more than evident from the current study that the reaction can proceed by both mechanisms, depending on the substituent on the terminal alkyne, although a recent study strongly supports the predominance of the initial cyclometalation on an alkene over an alkyne.[22] It is presumed that the reaction progresses via cycle b in the substrate with the ethoxycarbonyl group on the alkyne. In other words, the construction of medium-sized rings, which is a challenging task in organic chemistry, is achieved by the modification of the substrates suitable for cycle b.

In conclusion, the synthesis of various heterocycles having a dienamide unit was attempted by RCM of ene-ynamides. The reaction proceeded smoothly to provide the products in high yields in the synthesis of quinoline and isoquinoline derivatives, and the argon atmosphere was acceptable for the synthesis of quinoline derivatives. The introduction of an ethoxycarbonyl group on the terminal alkyne of the ene-ynamide was conducive for the construction of the seven-membered ring, although the synthesis of benzodiazepine derivatives from non-substituted ene-ynamides was difficult. Further, the presence of an ethoxycarbonyl group on the terminal alkyne of the ene-ynamides and an argon atmosphere under the given reaction conditions were necessary for the formation of the eight-membered ring. In particular, an eight-membered ring could be constructed under these reaction conditions; thus, this method would serve as a useful strategy for the construction of eight-membered rings, which is a challenging task in organic chemistry.

The metathesis reactions were carried out under an atmosphere of ethylene (1 atm) or an argon atmosphere (1 atm). All other manipulations were carried out under an atmosphere of argon, unless otherwise mentioned. Ru complexes were purchased from Aldrich Chemical Company. All other solvents and reagents were purified when necessary using standard procedure. Column chromatography was performed on silica gel 60 N (spherical, neutral, 40–60 μm, Kanto Chemical Co.). IR spectra were recorded on PerkinElmer FT-IR 1725X spectrophotometer. ¹H and ¹³C NMR spectra were recorded on a Jeol JNM-EX400 (¹H: 400 MHz, ¹³C: 100 MHz) spectrometer. Chemical shift values were reported in ppm (δ) downfield from TMS as an internal standard, or residual solvent peak [¹H NMR, CHCl₃ (7.24): ¹³C NMR, CHCl₃ (77.0)]. Coupling constants (J) are reported in hertz (Hz). EI mass spectra were recorded on a Jeol JMN-DX 303/JMA-DA 5000 mass spectrometer.

N-(2-Allylphenyl)-N-formyl-p-toluenesulfonamide (5)

To a solution of 2 (1.37 g, 4.77 mmol) in THF (25 mL) was added BuLi (3.6 mL, 5.72 mmol, 1.58 M hexane solution) slowly at –78 °C, and stirred at the same temperature for 1 h. To the resulting mixture was added 1-formylbenzotriazole (1.40 g, 9.53 mmol), and warmed to –30 °C for 1 h. Sat. aq NH₄Cl was added, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, and dried (MgSO₄). The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/Et₂O 3:1) to provide 5 (1.15 g, 77%) as a colorless oil.

IR (neat): 1715 (s), 1597 (m), 1361 (s), 1172 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 9.29 (br, 1 H), 7.61 (d, J = 8.2 Hz, 2 H), 7.40–7.29 (m, 4 H), 7.16 (dt, J = 1.5, 7.7 Hz, 1 H), 6.66 (d, J = 7.7 Hz, 1 H), 5.68 (dddd, J = 6.3, 7.3, 10.1, 16.9 Hz, 1 H), 5.08–5.00 (m, 2 H), 3.19 (dd, J = 7.3, 15.9 Hz, 1 H), 2.99 (dd, J = 6.3, 15.9 Hz, 1 H), 2.47 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 161.1, 145.8, 140.4, 135.3, 134.5, 130.4, 130.2, 130.1, 130.1, 129.9, 128.2, 127.1, 117.2, 35.1, 21.7.

MS (EI): m/z = 315 (M⁺), 287, 160, 132, 117, 91.

HRMS (EI): m/z calcd for C₁₇H₁₇NO₃S (M⁺): 315.0929; found: 315.0926.

N-Formyl-N-(2-vinylbenzyl)-p-toluenesulfonamide (6)

According to the procedure for the synthesis of 5, a solution of 3 (1.76 g, 6.12 mmol), BuLi (4.7 mL, 7.35 mmol, 1.58 M hexane solution) and 1-formylbenzotriazole (1.80 g, 12.25 mmol) in THF (30 mL) was stirred at 0 °C for 1 h to afford 6 (1.54 g, 80%) after purification by column chromatography on silica gel (hexane/EtOAc 5:1) as a colorless oil.

IR (neat): 1699 (s), 1597 (m), 1361 (s), 1166 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 9.21 (s, 1 H), 7.40 (d, J = 8.2 Hz, 2 H), 7.26–7.09 (m, 6 H), 6.85 (dd, J = 11.1, 17.4 Hz, 1 H), 5.36 (dd, J = 1.5, 17.4 Hz, 1 H), 5.25 (dd, J = 1.5, 11.1 Hz, 1 H), 4.87 (s, 2 H), 2.37 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 161.3, 144.9, 137.1, 135.2, 133.9, 131.0, 129.7, 128.9, 128.0, 127.7, 127.1, 126.2, 117.1, 42.9, 21.5.

MS (EI): m/z = 315 (M⁺), 160, 133, 115, 91.

HRMS (EI): m/z calcd for C₁₇H₁₇NO₃S (M⁺): 315.0929; found: 315.0922.

N-(2-Allylbenzyl)-N-formyl-p-toluenesulfonamide (7)

According to the procedure for the synthesis of 5, a solution of 4 (2.95 g, 9.78 mmol), BuLi (7.4 mL, 11.74 mmol, 1.58 M hexane solution) and 1-formylbenzotriazole (2.88 g, 19.57 mmol) in THF (50 mL) was stirred at 0 °C for 40 min to afford 7 (3.18 g, 99%) after purification by column chromatography on silica gel (hexane/Et₂O 2:1) as a colorless oil.

IR (neat): 1699 (s), 1597 (m), 1361 (s), 1166 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 9.24 (s, 1 H), 7.50 (d, J = 8.2 Hz, 2 H), 7.20 (d, J = 8.2 Hz, 2 H), 7.14 (d, J = 7.7 Hz, 1 H), 7.06–6.99 (m, 3 H), 5.86 (ddt, J = 10.3, 16.9, 6.0 Hz, 1 H), 5.05 (dd, J = 1.5, 10.3 Hz, 1 H), 4.88 (dd, J = 1.5, 16.9 Hz, 1 H), 4.77 (s, 2 H), 3.35 (d, J = 6.0 Hz, 2 H), 2.29 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 161.0, 144.8, 136.9, 135.9, 134.7, 132.0, 129.5, 129.2, 127.3, 127.2, 126.8, 126.1, 115.7, 42.2, 36.4, 21.0.

MS (EI): m/z = 329 (M⁺), 174, 130, 115, 91.

HRMS (EI): m/z calcd for C₁₈H₁₉NO₃S (M⁺): 329.1086; found: 329.1082.

N-(2-Allylphenyl)-N-(2,2-dichlorovinyl)-p-toluenesulfonamide (8)

To a solution of 5 (1.15 g, 3.65 mmol) and PPh₃ (2.39 g, 9.12 mmol) in THF (24 mL) was added CCl₄ (2.9 mL, 29.90 mmol) in THF (12 mL, total 0.1 M) at 60 °C over 3 h, and stirred at the same temperature for 1 h. After cooling the reaction mixture to r.t., sat. aq NaHCO₃ was added, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, and dried (MgSO₄). The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 10:1) to provide 8 (1.12 g, 81%) as a pale red oil.

IR (neat): 1598 (w), 1367 (s), 1170 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.55 (d, J = 8.3 Hz, 2 H), 7.33–7.28 (m, 4 H), 7.10 (s, 1 H), 7.08 (m, 1 H), 6.71 (d, J = 7.8 Hz, 1 H), 5.83 (m, 1 H), 5.15–5.10 (m, 2 H), 3.35 (d, J = 4.9 Hz, 2 H), 2.46 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.7, 140.7, 135.6, 135.2, 134.4, 130.0, 129.7, 129.7, 129.0, 127.8, 126.4, 125.9, 116.9, 112.8, 35.4, 21.5.

MS(EI): m/z = 381 (M⁺), 285, 226, 191, 150, 130, 115, 91.

HRMS (EI): m/z calcd for C₁₈H₁₇ ³⁵Cl₂NO₂S (M⁺): 381.0357; found: 381.0360.

N-(2,2-Dichlorovinyl)-N-(2-vinylbenzyl)-p-toluenesulfonamide (9)

According to the procedure for the synthesis of 8, a solution of 6 (1.42 g, 4.50 mmol), PPh₃ (2.95 g, 11.26 mmol) and CCl₄ (3.6 mL, 36.92 mmol) in THF (45 mL) was stirred at 60 °C for 12 h to afford 9 (1.53 g, 89%) as a pale yellow solid after purification by column chromatography on silica gel (hexane/EtOAc 10:1); mp 93 °C.

IR (KBr): 1596 (w), 1356 (m), 1164 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.73 (d, J = 8.2 Hz, 2 H), 7.48 (d, J = 7.7 Hz, 1 H), 7.35 (d, J = 8.2 Hz, 2 H), 7.29 (dd, J = 7.2, 7.7 Hz, 1 H), 7.21 (dd, J = 7.2, 7.7 Hz, 1 H), 7.17 (d, J = 7.7 Hz, 1 H), 7.07 (dd, J = 11.1, 17.4 Hz, 1 H), 6.04 (s, 1 H), 5.63 (dd, J = 1.5, 17.4 Hz, 1 H), 5.35 (dd, J = 1.5, 11.1 Hz, 1 H), 4.53 (s, 2 H), 2.46 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.3, 137.7, 135.0, 133.7, 131.4, 130.0, 129.9, 128.6, 128.0, 127.7, 127.5, 126.2, 124.5, 116.9, 50.8, 21.6.

MS (EI): m/z = 381 (M⁺), 285, 226, 117, 91.

HRMS (EI): m/z calcd for C₁₈H₁₇N³⁵Cl₂O₂S (M⁺): 381.0357; found: 381.0385.

N-(2-Allyl-benzyl)-N-(2,2-dichloro-vinyl)-p-toluenesulfonamide (10)

According to the procedure for the synthesis of 8, a solution of 7 (2.65 g, 8.05 mmol), PPh₃ (5.28 g, 20.13 mmol) and CCl₄ (6.4 mL, 66.02 mmol) in THF (40 mL) was stirred at 60 °C for 9 h to afford 10 (3.03 g, 95%) as a white solid after purification by column chromatography on silica gel (hexane/Et₂O 2:1); mp 72–73 °C.

IR (KBr): 1598 (w), 1356 (m), 1165 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.73 (d, J = 8.2 Hz, 2 H), 7.36 (d, J = 8.2 Hz, 2 H), 7.27–7.15 (m, 4 H), 6.05 (s, 1 H), 5.94 (ddt, J = 10.1, 16.9, 6.3 Hz, 1 H), 5.08 (ddt, J = 1.9, 10.1, 1.5 Hz, 1 H), 4.97 (ddt, J = 1.9, 16.9, 1.5 Hz, 1 H), 4.46 (s, 2 H), 3.50 (dt, J = 6.3, 1.5 Hz, 2 H), 2.47 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.3, 138.6, 136.5, 134.7, 132.4, 130.0, 129.9, 129.8, 128.4, 127.7, 127.4, 126.3, 124.7, 116.0, 50.8, 36.4, 21.5.

MS (EI): m/z = 395 (M⁺), 299, 155, 131, 105, 91.

HRMS (EI): m/z calcd for C₁₉H₁₉ ³⁵Cl₂NO₂S (M⁺): 395.0514; found: 395.0492.

N-(2-Allylphenyl)-N-ethynyl-p-toluenesulfonamide (11a)

To a solution of 8 (228.1 mg, 0.60 mmol) in THF (10 mL) was added BuLi (0.85 mL, 1.31 mmol, 1.55 M hexane solution) at –78 °C, and stirred at the same temperature for 0.5 h. Sat. aq NH₄Cl was added, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, and dried (MgSO₄). The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 10:1) to provide 11a (157.5 mg, 85%) as a white solid; mp 87–88 °C.

IR (KBr): 2131 (m), 1597 (w), 1369 (s), 1168 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.71 (d, J = 8.2 Hz, 2 H), 7.36 (d, J = 8.2 Hz, 2 H), 7.32–7.29 (m, 2 H), 7.12 (m, 1 H), 6.82 (d, J = 7.7 Hz, 1 H), 5.91 (ddt, J = 10.6, 16.9, 6.8 Hz, 1 H), 5.15–5.09 (m, 2 H), 3.49 (br, 2 H), 2.76 (s, 1 H), 2.47 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 145.1, 139.6, 136.4, 135.6, 133.6, 130.4, 129.5, 129.5, 128.2, 127.6, 127.0, 116.7, 76.9, 57.7, 35.2, 21.5.

MS (EI): m/z = 311 (M⁺), 263, 246, 156, 128, 91.

HRMS (EI): m/z calcd for C₁₈H₁₇NO₂S (M⁺): 311.0980; found: 311.0979.

Ethyl [(2-Allylphenyl)-(p-toluenesulfonyl)amino]propynoate (11b)

To a solution of 8 (0.33 g, 0.86 mmol) in THF (17 mL) was added BuLi (1.2 mL, 1.90 mmol, 1.58 M hexane solution) at –78 °C, and stirred at the same temperature for 0.5 h. To the resulting mixture was added ethyl chlorocarbonate (0.17 mL, 1.73 mmol) and warmed to –50 °C over 0.5 h. Sat. aq NH₄Cl was added, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine and dried (MgSO₄). The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 10:1) to provide 11b (0.25 g, 76%) as a pale yellow oil.

IR (neat): 2220 (s), 1706 (s), 1597 (w), 1375 (s), 1177 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.75 (d, J = 8.2 Hz, 2 H), 7.40–7.30 (m, 4 H), 7.16 (ddd, J = 1.9, 6.8, 8.2 Hz, 1 H), 6.83 (dd, J = 1.0, 7.7 Hz, 1 H), 5.87 (ddt, J = 10.6, 17.4, 6.8 Hz, 1 H), 5.14–5.07 (m, 2 H), 4.22 (q, J = 7.3 Hz, 2 H), 3.40 (br, 2 H), 2.49 (s, 3 H), 1.30 (t, J = 7.3 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 153.9, 145.9, 139.4, 135.3, 135.2, 133.2, 130.6, 130.1, 129.9, 128.4, 127.8, 127.2, 117.1, 82.6, 65.9, 61.4, 35.1, 21.6, 14.0.

MS (EI): m/z = 383 (M⁺), 338, 319, 290, 272, 244, 228, 154, 128, 115, 91.

HRMS (EI): m/z calcd for C₂₁H₂₁NO₄S (M⁺): 383.1191; found: 383.1185.

N-Ethynyl-N-(2-vinylbenzyl)-p-toluenesulfonamide (12a)

According to the procedure for the synthesis of 11a, a solution of 9 (305.9 mg, 0.80 mmol) and BuLi (1.1 mL, 1.76 mmol, 1.58 M hexane solution) in THF (16 mL) was stirred at –78 °C for 1 h to afford 12a (209.6 mg, 84%) as a white solid after purification by column chromatography on silica gel (hexane/EtOAc 10:1); mp 88–89 °C.

IR (KBr): 2141 (m), 1596 (w), 1360 (s), 1174 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.79 (d, J = 8.2 Hz, 2 H), 7.49 (d, J = 7.7 Hz, 1 H), 7.34 (d, J = 8.2 Hz, 2 H), 7.29 (ddd, J = 1.9, 7.3, 7.7 Hz, 1 H), 7.24–7.17 (m, 2 H), 7.01 (dd, J = 11.1, 17.4 Hz, 1 H), 5.62 (dd, J = 1.5, 17.4 Hz, 1 H), 5.32 (dd, J = 1.5, 11.1 Hz, 1 H), 4.52 (s, 2 H), 2.59 (s, 1 H), 2.45 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.8, 137.5, 133.9, 133.3, 130.5, 130.3, 129.7, 128.7, 127.6, 127.5, 125.9, 117.0, 75.8, 59.8, 52.4, 21.5.

MS (EI): m/z = 310 (M⁺ – 1), 156, 129, 117, 91.

HRMS (EI): m/z calcd for C₁₈H₁₇NO₂S (M⁺): 311.0980; found: 311.0992.

Ethyl [(p-Toluenesulfonyl)-(2-vinylbenzyl)amino]propynoate (12b)

According to the procedure for the synthesis of 11b, a solution of 9 (313.3 mg, 0.82 mmol), BuLi (1.2 mL, 1.97 mmol, 1.58 M hexane solution), and ethyl chlorocarbonate (0.16 mL, 1.64 mmol) in THF (16 mL) was stirred at –50 °C for 0.5 h to afford 12b (240.7 mg, 77%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/benzene 2:3).

IR (neat): 2219 (s), 1702 (s), 1375 (m), 1172 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.75 (d, J = 8.7 Hz, 2 H), 7.47 (d, J = 7.2 Hz, 1 H), 7.34–7.29 (m, 3 H), 7.24–7.21 (m, 2 H), 6.94 (dd, J = 10.9, 17.2 Hz, 1 H), 5.59 (dd, J = 1.2, 17.2 Hz, 1 H), 5.33 (dd, J = 1.2, 10.9 Hz, 1 H), 4.67 (s, 2 H), 4.14 (q, J = 7.2 Hz, 2 H), 2.46 (s, 3 H), 1.25 (t, J = 7.2 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 153.8, 145.4, 137.7, 133.9, 133.2, 130.3, 130.3, 129.9, 129.1, 127.8, 127.8, 126.3, 117.6, 82.5, 68.1, 61.4, 52.7, 21.6, 14.0.

MS (EI): m/z = 383 (M⁺), 228, 182, 154, 129, 117, 91.

HRMS (EI): m/z calcd for C₂₁H₂₁NO₄S (M⁺): 383.1191; found: 383.1194.

N-Phenylethynyl-N-(2-vinylbenzyl)-p-toluenesulfonamide (12c)

To a solution of 9 (239.0 mg, 0.63 mmol) in THF (8 mL) was added BuLi (0.87 mL, 1.38 mmol, 1.58 M hexane solution) at –78 °C, and stirred at the same temperature for 0.5 h. To the resulting mixture was added ZnBr₂ (168.9 mg, 0.75 mmol) in THF (2 mL), and stirred at r.t. for 0.5 h to provide the crude alkynylzinc solution. This alkynylzinc solution was transferred with THF (3 mL) to the alkylpalladium complex in THF solution (5 mL), which was prepared from PhI (0.08 mL, 0.75 mmol), Pd₂(dba)₃·CHCl₃ (32.4 mg, 31.26 μmol) and PPh₃ (32.8 mg, 0.13 mmol). The resulting mixture was stirred at r.t. for 21 h. After the volatiles were removed under reduced pressure, brine was added and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, and dried (MgSO₄). The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 10:1) to provide 12c (134.9 mg, 56%) as a pale yellow oil.

IR (neat): 2238 (s), 1598 (m), 1366 (s), 1170 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.85 (d, J = 8.2 Hz, 2 H), 7.52 (d, J = 7.7 Hz, 1 H), 7.38–7.27 (m, 5 H), 7.25–7.14 (m, 5 H), 7.07 (dd, J = 11.1, 17.4 Hz, 1 H), 5.65 (dd, J = 1.0, 17.4 Hz, 1 H), 5.33 (dd, J = 1.0, 11.1 Hz, 1 H), 4.61 (s, 2 H), 2.46 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.7, 137.8, 134.0, 133.4, 130.8, 130.7, 129.7, 128.8, 128.0, 127.7, 127.6, 127.4, 126.8, 126.0, 122.7, 117.0, 82.4, 71.5, 52.8, 21.6.

MS (EI): m/z = 387 (M⁺), 248, 232, 217, 155, 117, 91.

HRMS (EI): m/z calcd for C₂₄H₂₁NO₂S (M⁺): 387.1293; found: 387.1291.

N-(2-Allylbenzyl)-N-ethynyl-p-toluenesulfonamide (13a)

According to the procedure for the synthesis of 11a, a solution of 10 (182.5 mg, 0.46 mmol) and BuLi (0.64 mL, 1.01 mmol, 1.58 M hexane solution) in THF (9 mL) was stirred at –78 °C for 1 h to afford 13a (131.5 mg, 88%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 10:1).

IR (neat): 2132 (w), 1597 (w), 1369 (m), 1173 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.80 (d, J = 8.2 Hz, 2 H), 7.36 (d, J = 8.2 Hz, 2 H), 7.30–7.14 (m, 4 H), 5.93 (ddt, J = 10.1, 16.9, 6.0 Hz, 1 H), 5.06 (dd, J = 1.5, 10.1 Hz, 1 H), 4.96 (dd, J = 1.5, 16.9 Hz, 1 H), 4.47 (s, 2 H), 3.45 (d, J = 6.0 Hz, 2 H), 2.60 (s, 1 H), 2.47 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.8, 138.7, 136.4, 133.9, 131.7, 130.3, 129.9, 129.7, 128.7, 127.6, 126.3, 116.0, 76.0, 59.7, 52.4, 36.5, 21.5.

MS (EI): m/z = 324 (M⁺ – 1), 260, 170, 143, 131, 117, 91.

HRMS (EI): m/z calcd for C₁₉H₁₉NO₂S (M⁺): 325.1136; found: 325.1143.

Ethyl [(2-Allylbenzyl)-(p-toluenesulfonyl)amino]propynoate (13b)

According to the procedure for the synthesis of 11b, a solution of 10 (179.5 mg, 0.45 mmol), BuLi (0.69 mL, 1.09 mmol, 1.58 M hexane solution), and ethyl chlorocarbonate (0.09 mL, 0.91 mmol) in THF (9 mL) was stirred at –10 °C for 2 h to afford 13b (142.7 mg, 79%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 10:1).

IR (neat): 2218 (s), 1705 (s), 1597 (w), 1375 (s), 1172 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.76 (d, J = 8.2 Hz, 2 H), 7.34 (d, J = 8.2 Hz, 2 H), 7.28 (dt, J = 1.9, 7.2 Hz, 1 H), 7.25–7.14 (m, 3 H), 5.91 (ddt, J = 10.1, 16.9, 5.8 Hz, 1 H), 5.06 (dd, J = 1.5, 10.1 Hz, 1 H), 4.94 (dd, J = 1.5, 16.9 Hz, 1 H), 4.60 (s, 2 H), 4.14 (q, J = 7.2 Hz, 2 H), 3.41 (d, J = 5.8 Hz, 2 H), 2.46 (s, 3 H), 1.25 (t, J = 7.2 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 14.0, 21.6, 36.6, 52.5, 61.4, 68.0, 82.6, 116.2, 126.6, 127.8, 129.0, 129.9, 130.1, 130.2, 131.1, 133.9, 136.3, 138.6, 145.5, 153.9.

MS (EI): m/z = 398 (M⁺ + 1), 242, 196, 155, 131, 117, 91.

HRMS (EI): m/z calcd for C₂₂H₂₃NO₄S (M⁺): 397.1348; found: 397.1344.

N-(2,2-Dichlorovinyl)-N-hex-5-enyl-p-toluenesulfonamide (16)

To a solution of 14 (2.99 g, 15.00 mmol), 15 (2.5 mL, 20.41 mmol), and PPh₃ (5.51 g, 21.01 mmol) in THF (30 mL) was added DEAD (8.9 mL, 19.51 mmol) at 0 °C, and the mixture was stirred at r.t. for 4 h. The volatiles were removed under reduced pressure, and the residue passed through a short column of silica gel (eluent: hexane/EtOAc 5:1) to provide the crude alkylated formyltosylamide. To a solution of this crude product and PPh₃ (9.84 g, 37.50 mmol) in THF (30 mL) was added CCl₄ (12 mL, 123.00 mmol) in THF (10 mL) at 60 °C over 3 h, and the resulting mixture was stirred at the same temperature for 12 h. Sat. aq NaHCO₃ was added after cooling to r.t., and the aqueous phase was extracted with Et₂O. The combined organic phases were washed with brine, and dried (MgSO₄). The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 10:1) to provide 16 (2.91 g, 56%) as a white solid; mp 90 °C.

IR (KBr): 1599 (w), 1356 (s), 1165 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.69 (d, J = 8.2 Hz, 2 H), 7.33 (d, J = 8.2 Hz, 2 H), 6.28 (s, 1 H), 5.76 (ddt, J = 10.2, 16.9, 6.8 Hz, 1 H), 5.02–4.94 (m, 2 H), 3.33 (t, J = 7.2 Hz, 2 H), 2.44 (s, 3 H), 2.05 (dt, J = 6.8, 7.2 Hz, 2 H), 1.56–1.48 (m, 2 H), 1.42–1.36 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.1, 138.1, 135.5, 129.8, 127.2, 124.9, 124.3, 114.9, 48.9, 33.1, 27.8, 25.7, 21.6.

MS (EI): m/z = 347 (M⁺), 264, 251, 192, 155, 91.

HRMS (EI): m/z calcd for C₁₅H₁₉ ³⁵Cl₂NO₂S (M⁺): 347.0514; found: 347.0522.

N-Ethynyl-N-hex-5-enyl-p-toluenesulfonamide (17a)

According to the procedure for the synthesis of 11a, a solution of 16 (206.2 mg, 0.59 mmol) and BuLi (0.82 mL, 1.30 mmol, 1.58 M hexane solution) in THF (10 mL) was stirred at –78 °C for 1 h to afford 17a (140.0 mg, 85%) as a white solid after purification by column chromatography on silica gel (hexane/EtOAc 10:1); mp 43 °C.

IR (KBr): 2133 (m), 1598 (w), 1359 (s), 1169 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.80 (d, J = 8.2 Hz, 2 H), 7.35 (d, J = 8.2 Hz, 2 H), 5.75 (ddt, J = 10.1, 16.9, 6.3 Hz, 1 H), 5.02–4.93 (m, 2 H), 3.31 (t, J = 7.3 Hz, 2 H), 2.73 (s, 1 H), 2.45 (s, 3 H), 2.05 (dt, J = 6.3, 7.3 Hz, 2 H), 1.66 (tt, J = 7.3, 7.7 Hz, 2 H), 1.41 (tt, J = 7.3, 7.7 Hz, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.6, 138.0, 134.4, 129.7, 127.5, 114.8, 75.9, 59.0, 50.8, 32.9, 26.9, 25.2, 21.5.

MS (EI): m/z = 276 (M⁺ – 1), 212, 155, 122, 91.

HRMS (EI): m/z calcd for C₁₅H₁₉O₂NS (M⁺): 277.1136; found: 277.1122.

Ethyl [Hex-5-enyl-(p-toluenesulfonyl)amino]propynoate (17b)

According to the procedure for the synthesis of 11b, a solution of 16 (313.0 mg, 0.90 mmol), BuLi (1.3 mL, 2.16 mmol, 1.63 M hexane solution), and ethyl chlorocarbonate (0.17 mL, 1.80 mmol) in THF (18 mL) was stirred at –20 °C for 1.5 h to afford 17b (223.3 mg, 71%) as a colorless oil after purification by column chromatography on silica gel (hexane/Et₂O 3:1).

IR (neat): 2219 (s), 1705 (s), 1597 (w), 1376 (s), 1174 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.82 (d, J = 8.2 Hz, 2 H), 7.38 (d, J = 8.2 Hz, 2 H), 5.73 (ddt, J = 10.1, 16.9, 6.3 Hz, 1 H), 5.02–4.93 (m, 2 H), 4.23 (q, J = 7.2 Hz, 2 H), 3.42 (t, J = 7.3 Hz, 2 H), 2.46 (s, 3 H), 2.08–2.01 (m, 2 H), 1.72–1.63 (m, 2 H), 1.42–1.33 (m, 2 H), 1.31 (t, J = 7.2 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 154.2, 145.4, 137.8, 134.2, 130.0, 127.7, 115.1, 82.4, 67.7, 61.5, 51.2, 32.9, 27.3, 25.2, 21.7, 14.1.

MS (EI): m/z = 348 (M⁺ – 1), 304, 194, 166, 148, 91.

HRMS (EI): m/z calcd for C₁₈H₂₃O₄NS (M⁺): 349.1348; found: 349.1339.

N-[2-(N-Allyl-N-p-toluenesulfonylamino)phenyl]-N-ethynyl-p-toluenesulfonamide (21a)

To a solution of 21d (243.1 mg, 0.44 mmol) in THF (4 mL) was added TBAF (1.3 mL, 1.32 mmol, 1 M THF solution) at 0 °C, and stirred at the same temperature for 5 min. Sat. aq NH₄Cl was added, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine and dried (MgSO₄). The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 2:1) to provide 21a (194.1 mg, 92%) as a white solid; mp 146 °C.

IR (KBr): 2130 (w), 1596 (m), 1372 (m), 1165 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.85 (d, J = 8.2 Hz, 2 H), 7.84 (d, J = 7.7 Hz, 2 H), 7.41–7.25 (m, 6 H), 7.20 (dd, J = 1.5, 7.7 Hz, 1 H), 6.99 (dd, J = 1.5, 7.7 Hz, 1 H), 5.95 (ddt, J = 10.1, 16.9, 6.8 Hz, 1 H), 5.09–5.02 (m, 2 H), 4.22 (d, J = 6.8 Hz, 2 H), 2.72 (s, 1 H), 2.49 (s, 3 H), 2.45 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 145.3, 143.8, 138.3, 137.6, 136.1, 133.5, 133.2, 131.4, 129.8, 129.6, 129.5, 129.1, 129.0, 128.7, 128.5, 119.3, 77.2, 58.1, 54.4, 21.8, 21.6.

MS (EI): m/z = 480 (M⁺), 325, 262, 171, 139, 91.

HRMS (EI): m/z calcd for C₂₅H₂₄N₂O₄S₂ (M⁺): 480.1177; found: 480.1180.

Ethyl {[2-(Allyl-p-toluenesulfonylamino)phenyl]-p-toluenesulfonylamino}propynoate (21b)

To a solution of 21a (305.9 mg, 0.64 mmol) in THF (13 mL) was added BuLi (0.42 mL, 0.70 mmol, 1.65 M hexane solution) at –78 °C, and stirred at the same temperature for 0.5 h. To the resulting mixture was added ethyl chlorocarbonate (0.07 mL, 0.76 mmol), and warmed to –15 °C for 1.5 h. Sat. aq NH₄Cl solution was added, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine and dried (MgSO₄). The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/Et₂O Ac 2:1) to provide 21b (252.2 mg, 72%) as a white solid; mp 48 °C.

IR (KBr): 2221 (s), 1706 (s), 1597 (w), 1374 (m), 1176 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.90 (d, J = 8.7 Hz, 2 H), 7.74 (d, J = 8.2 Hz, 2 H), 7.41 (d, J = 8.7 Hz, 2 H), 7.30 (d, J = 8.2 Hz, 2 H), 7.39–7.28 (m, 2 H), 7.13 (dd, J = 1.5, 7.7 Hz, 1 H), 7.05 (dd, J = 1.9, 7.7 Hz, 1 H), 5.93 (ddt, J = 9.7, 16.9, 7.2 Hz, 1 H), 5.09–5.02 (m, 2 H), 4.21–4.15 (m, 4 H), 2.49 (s, 3 H), 2.44 (s, 3 H), 1.26 (t, J = 7.2 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 153.9, 146.0, 143.9, 137.8, 136.6, 135.6, 133.0, 132.9, 131.3, 130.0, 129.8, 129.5, 129.2, 129.2, 128.6, 128.6, 119.6, 83.1, 66.5, 61.5, 54.6, 21.8, 21.6, 14.1.

MS (EI): m/z = 552 (M⁺), 507, 397, 334, 259, 243, 169, 139, 91.

HRMS(EI): m/z calcd for C₂₈H₂₈N₂O₆S₂ (M⁺): 552.1389; found: 552.1385.

N-[2-(N-Allyl-N-p-toluenesulfonylamino)phenyl]-N-(2-phenylethynyl)-p-toluenesulfonamide (21c)

To a mixture of Pd(PPh₃)₄ (13.4 mg, 11.59 µmol), CuI (2.2 mg, 11.59 μmol), and PhI (0.05 mL, 0.46 mmol) in Et₃N (2 mL) and benzene (1 mL) was added 21a (111.4 mg, 0.23 mmol) at r.t., and the mixture was stirred at the same temperature for 48 h. The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc, 2:1) to provide 21c (126.4 mg, 98%) as a white solid; mp 53 °C.

IR (KBr): 2241 (w), 1597 (w), 1356 (m), 1168 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.92–7.86 (m, 4 H), 7.41–7.24 (m, 12 H), 7.05 (d, J = 8.3 Hz, 1 H), 5.97 (ddt, J = 9.8, 16.6, 6.8 Hz, 1 H), 5.10–5.02 (m, 2 H), 4.27 (d, J = 6.8 Hz, 2 H), 2.49 (s, 3 H), 2.38 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 145.2, 143.7, 138.1, 138.0, 136.5, 133.8, 133.3, 131.9, 131.4, 129.6, 129.6, 129.5, 129.1, 128.9, 128.7, 128.6, 128.2, 127.8, 122.7, 119.4, 83.8, 69.8, 54.4, 21.7, 21.6.

MS (EI): m/z = 556 (M⁺), 456, 417, 401, 301, 245, 139, 119, 91.

HRMS (EI): m/z calcd for C₃₁H₂₈O₄N₂S₂ (M⁺): 556.1490; found: 556.1497.

N-[2-(N-Allyl-N-p-toluenesulfonylamino)phenyl]-N-(2-trimethylsilyl)ethynyl-p-toluenesulfonamide (21d)

To a solution of 19 (811.2 mg, 1.78 mmol) in THF (27 mL) was added BuLi (1.3 mL, 1.95 mmol, 1.55 M hexane solution) at –78 °C, and stirred at the same temperature for 1 h. To the resulting mixture was added phenyl(trimethylsilylethynyl)iodonium triflate (960.0 mg, 2.13 mmol). The mixture was warmed to r.t. over 1 h, and stirred at the same temperature for 18 h. Sat. aq NH₄Cl was added, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine and dried (MgSO₄). The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 2:1) to provide 21d (595.4 mg, 61%) as a white solid; mp 35–36 °C.

IR (KBr): 2165 (m), 1597 (w), 1359 (m), 1173 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.94 (d, J = 8.3 Hz, 2 H), 7.83 (d, J = 8.3 Hz, 2 H), 7.39–7.24 (m, 7 H), 7.01 (dd, J = 1.0, 7.3 Hz, 1 H), 5.93 (ddt, J = 9.8, 16.6, 6.8 Hz, 1 H), 5.05–4.99 (m, 2 H), 4.17 (d, J = 6.8 Hz, 2 H), 2.49 (s, 3 H), 2.45 (s, 3 H), 0.12 (s, 9 H).

¹³C NMR (100 MHz, CDCl₃): δ = 145.1, 143.7, 137.9, 137.4, 136.4, 133.6, 133.2, 131.7, 129.5, 129.4, 129.4, 129.1, 129.0, 128.9, 128.4, 119.4, 95.9, 72.6, 54.1, 21.7, 21.6, –0.1.

MS (EI): m/z = 552 (M⁺), 537, 397, 241, 169, 91.

HRMS (EI): m/z calcd for C₂₈H₃₂N₂O₄S₂Si (M⁺): 552.1573; found: 552.1567.

N-(2,2-Dichlorovinyl)-N-hept-6-enyl-p-toluenesulfonamide (26)

To a solution of 14 (3.00 g, 15.06 mmol), 23 (2.7 mL, 20.33 mmol), and PPh₃ (5.53 g, 21.08 mmol) in THF (30 mL) was added DEAD (8.9 mL, 19.58 mmol) at 0 °C, and the mixture was stirred at r.t. for 4 h. The volatiles were removed under reduced pressure, and the residue was passed through a short column of silica gel (eluent: hexane/EtOAc 5:1) to provide the crude alkylated formyltosylamide. To a solution of this crude product and PPh₃ (9.87 g, 37.64 mmol) in THF (30 mL) was added CCl₄ (12 mL, 123.48 mmol) in THF (10 mL) at 60 °C for 3 h, and the resulting mixture was stirred at the same temperature for 7 h. Sat. aq NaHCO₃ was added after cooling to r.t., and the aqueous phase was extracted with Et₂O. The combined organic phases were washed with brine and dried (MgSO₄). The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/Et₂O 10:1) to provide 26 (2.59 g, 48%) as a white solid; mp 69 °C.

IR (KBr): 1599 (w), 1354 (s), 1165 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.69 (d, J = 8.5 Hz, 2 H), 7.33 (d, J = 8.5 Hz, 2 H), 6.27 (s, 1 H), 5.78 (ddt, J = 10.1, 16.9, 6.8 Hz, 1 H), 5.02–4.92 (m, 2 H), 3.31 (t, J = 7.5 Hz, 2 H), 2.44 (s, 3 H), 2.03 (dt, J = 6.8, 7.2 Hz, 2 H), 1.56–1.47 (m, 2 H), 1.42–1.26 (m, 4 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.1, 138.6, 135.5, 129.8, 127.2, 124.9, 124.3, 114.6, 49.0, 33.5, 28.3, 28.2, 26.0, 21.6.

MS (EI): m/z = 361 (M⁺), 278, 265, 206, 155, 91.

HRMS (EI): m/z calcd for C₁₆H₂₁ ³⁵Cl₂NO₂S (M⁺): 361.0607; found: 361.0667.

N-[4,4-Bis(benzyloxymethyl)hept-6-enyl]-N-(2,2-dichlorovinyl)-p-toluenesulfonamide (27)

According to the procedure for the synthesis of 26, a solution of 14 (0.799 g, 4.01 mmol), 24 (1.09 g, 3.09 mmol), PPh₃ (1.01 g, 3.86 mmol), and DEAD (1.7 mL, 3.70 mmol) in THF (6 mL) was stirred at r.t. for 1 h and then a solution of the crude product obtained, an additional amount of PPh₃ (2.02 g, 7.72 mmol), and CCl₄ (2.4 mL, 25.31 mmol) in THF (9 mL) were stirred at 60 °C for 24 h to afford 27 (811.2 mg, 44%) as a colorless oil after purification by column chromatography on silica gel (hexane/EtOAc 10:1).

IR (neat): 1639 (w), 1598 (w), 1360 (s), 1167 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.66 (d, J = 8.7 Hz, 2 H), 7.36–7.25 (m, 12 H), 6.29 (s, 1 H), 5.77–5.65 (m, 1 H), 5.04–4.98 (m, 2 H), 4.45 (s, 4 H), 3.30–3.23 (m, 6 H), 2.42 (s, 3 H), 2.07 (d, J = 7.7 Hz, 2 H), 1.54–1.44 (m, 2 H), 1.28–1.22 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 143.9, 138.6, 135.3, 133.9, 129.7, 128.1, 128.1, 127.2, 127.0, 124.8, 123.0, 117.5, 73.0, 72.4, 49.5, 41.2, 36.4, 28.9, 22.0, 21.4.

MS (EI): m/z = 601 (M⁺), 510, 446, 355, 340, 249, 155, 91.

HRMS (EI): m/z calcd for C₃₂H₃₇ ³⁵Cl₂NO₄S (M⁺): 601.1820; found: 601.1814.

N-[3-(5-Allyl-2,2-dimethyl[1,3]dioxan-5-yl)-propyl]-N-(2,2-dichlorovinyl)-p-toluenesulfonamide (28)

According to the procedure for the synthesis of 26, a solution of 14 (784.3 mg, 3.94 mmol), 25 (703.0 mg, 3.28 mmol), PPh₃ (1.205 g, 4.59 mmol), and DEAD (1.9 mL, 4.26 mmol) in THF (15 mL) was stirred at r.t. for 4 h and then a solution of the crude product obtained, an additional amount of PPh₃ (2.15 g, 8.20 mmol), and CCl₄ (2.6 mL, 26.90 mmol) in THF (15 mL) were stirred at 60 °C for 17 h to afford 28 (707.1 mg, 47%) as a white solid after purification by column chromatography on silica gel (hexane/EtOAc 5:1); 54 °C.

IR (KBr): 1598 (w), 1354 (s), 1167 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.68 (d, J = 8.2 Hz, 2 H), 7.33 (d, J = 8.2 Hz, 2 H), 6.31 (s, 1 H), 5.70 (ddt, J = 10.1, 17.9, 7.2 Hz, 1 H), 5.12–5.05 (m, 2 H), 3.56 (d, J = 11.6 Hz, 2 H), 3.50 (d, J = 11.6 Hz, 2 H), 3.31 (t, J = 7.2 Hz, 2 H), 2.44 (s, 3 H), 2.11 (d, J = 7.2 Hz, 2 H), 1.53–1.43 (m, 2 H), 1.40 (s, 3 H), 1.39 (s, 3 H), 1.34–1.28 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.2, 135.5, 133.0, 129.9, 127.3, 124.8, 123.9, 118.4, 98.1, 67.5, 49.6, 36.6, 35.0, 29.2, 23.9, 23.6, 21.9, 21.6.

MS (EI): m/z = 461 (M⁺), 446, 306, 277, 248, 155, 91.

HRMS (EI): m/z calcd for C₂₁H₂₉ ³⁵Cl₂NO₄S (M⁺): 461.1194; found: 461.1175.

N-Ethynyl-N-hept-6-enyl-p-toluenesulfonamide (29a)

According to the procedure for the synthesis of 11a, a solution of 26 (235.7 mg, 0.65 mmol) and BuLi (0.88 mL, 1.43 mmol, 1.63 M hexane solution) in THF (13 mL) was stirred at –78 °C for 20 min to afford 29a (158.8 mg, 84%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 10:1).

IR (neat): 2133 (m), 1597 (w), 1366 (s), 1169 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.80 (d, J = 8.2 Hz, 2 H), 7.35 (d, J = 8.2 Hz, 2 H), 5.78 (ddt, J = 10.1, 16.9, 6.8 Hz, 1 H), 5.02–4.91 (m, 2 H), 3.29 (t, J = 7.3 Hz, 2 H), 2.73 (s, 1 H), 2.45 (s, 3 H), 2.02 (dt, J = 6.8, 7.2 Hz, 2 H), 1.69–1.60 (m, 2 H), 1.42–1.27 (m, 4 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.6, 138.5, 134.5, 129.7, 127.5, 114.5, 75.9, 59.0, 51.0, 33.4, 28.2, 27.4, 25.5, 21.6.

MS (EI): m/z = 290 (M⁺ – 1), 227, 155, 136, 91.

HRMS (EI): m/z calcd for C₁₆H₂₁NO₂S (M⁺): 291.1293; found: 291.1298.

Ethyl [Hept-6-enyl-(p-toluenesulfonyl)amino]propynoate (29b)

According to the procedure for the synthesis of 11b, a solution of 26 (287.3 mg, 0.79 mmol), BuLi (1.1 mL, 1.74 mmol, 1.63 M hexane solution), and ethyl chlorocarbonate (0.11 mL, 1.19 mmol) in THF (16 mL) was stirred at –30 °C for 1 h to afford 29b (228.6 mg, 79%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 10:1).

IR (neat): 2218 (s), 1705 (s), 1597 (w), 1376 (s), 1174 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.82 (d, J = 8.2 Hz, 2 H), 7.37 (d, J = 8.2 Hz, 2 H), 5.76 (ddt, J = 10.1, 16.9, 6.8 Hz, 1 H), 5.02–4.91 (m, 2 H), 4.23 (q, J = 7.2 Hz, 2 H), 3.41 (t, J = 7.3 Hz, 2 H), 2.46 (s, 3 H), 2.05–1.98 (m, 2 H), 1.71–1.62 (m, 2 H), 1.31 (t, J = 7.2 Hz, 3 H), 1.42–1.24 (m, 4 H).

¹³C NMR (100 MHz, CDCl₃): δ = 154.0, 145.4, 138.3, 134.1, 129.9, 127.5, 114.5, 82.3, 67.6, 61.4, 51.2, 33.3, 28.0, 27.6, 25.3, 21.5, 14.0.

MS (EI): m/z = 363 (M⁺), 318, 208, 162, 155, 91.

HRMS (EI): m/z calcd for C₁₉H₂₅NO₄S (M⁺): 363.1504; found: 363.1489.

N-[4,4-Bis(benzyloxymethyl)hept-6-enyl]-N-ethynyl-p-toluenesulfonamide (30a)

According to the procedure for the synthesis of 11a, a solution of 27 (305.5 mg, 0.51 mmol) and BuLi (0.68 mL, 1.12 mmol, 1.63 M hexane solution) in THF (10 mL) was stirred at –78 °C for 10 min to afford 30a (237.3 mg, 88%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 10:1).

IR (neat): 2135 (m), 1639 (w), 1597 (w), 1367 (s), 1169 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.77 (d, J = 8.2 Hz, 2 H), 7.35–7.25 (m, 12 H), 5.71 (m, 1 H), 5.04–4.97 (m, 2 H), 4.44 (s, 4 H), 3.28–3.21 (m, 6 H), 2.68 (s, 1 H), 2.42 (s, 3 H), 2.06 (d, J = 7.7 Hz, 2 H), 1.68–1.58 (m, 2 H), 1.30–1.23 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.5, 138.6, 134.4, 133.9, 129.6, 128.1, 127.4, 127.2, 127.2, 117.6, 75.9, 73.0, 72.4, 59.0, 51.7, 41.3, 36.3, 28.5, 21.4, 21.4.

MS (EI): m/z = 530 (M⁺ – 1), 440, 376, 270, 91.

HRMS (EI): m/z calcd for C₃₂H₃₇O₄NS (M⁺): 531.2443; found: 531.2467.

Ethyl {[4,4-Bis(benzyloxymethyl)hept-6-enyl](p-toluenesulfonyl)amino}propynoate (30b)

According to the procedure for the synthesis of 11b, a solution of 27 (444.4 mg, 0.74 mmol), BuLi (1.0 mL, 1.62 mmol, 1.63 M hexane solution), and ethyl chlorocarbonate (0.08 mL, 0.88 mmol) in THF (15 mL) was stirred at –30 °C for 1 h to afford 30b (302.7 mg, 68%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 5:1).

IR (neat): 2218 (s), 1704 (s), 1598 (w), 1376 (s), 1174 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.78 (d, J = 8.7 Hz, 2 H), 7.35–7.25 (m, 12 H), 5.68 (m, 1 H), 5.04–4.97 (m, 2 H), 4.44 (s, 4 H), 4.19 (q, J = 7.3 Hz, 2 H), 3.35 (t, J = 7.3 Hz, 2 H), 3.25 (s, 2 H), 3.24 (s, 2 H), 2.43 (s, 3 H), 2.05 (d, J = 6.8 Hz, 2 H), 1.68–1.59 (m, 2 H), 1.27 (t, J = 7.3 Hz, 3 H), 1.26–1.20 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 153.9, 145.2, 138.5, 134.0, 133.7, 129.8, 128.1, 127.5, 127.2, 127.2, 117.6, 82.3, 73.0, 72.2, 67.7, 61.3, 51.9, 41.2, 36.3, 28.5, 21.7, 21.5, 14.0.

MS (EI): m/z = 603 (M⁺), 448, 342, 155, 91.

HRMS (EI): m/z calcd for C₃₅H₄₁NO₆S (M⁺): 603.2655; found: 603.2673.

N-[3-(5-Allyl-2,2-dimethyl[1,3]dioxan-5-yl)propyl]-N-ethynyl-p-toluenesulfonamide (31a)

According to the procedure for the synthesis of 11a, a solution of 28 (225.5 mg, 0.49 mmol) and BuLi (0.69 mL, 1.07 mmol, 1.55 M hexane solution) in THF (10 mL) was stirred at –78 °C for 0.5 h to afford 31a (161.8 mg, 85%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 3:1).

IR (neat): 2134 (m), 1597 (w), 1372(s), 1170 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.80 (d, J = 8.2 Hz, 2 H), 7.35 (d, J = 8.2 Hz, 2 H), 5.70 (ddt, J = 11.6, 16.9, 7.7 Hz, 1 H), 5.11–5.05 (m, 2 H), 3.55 (d, J = 11.6 Hz, 2 H), 3.50 (d, J = 11.6 Hz, 2 H), 3.29 (t, J = 7.0 Hz, 2 H), 2.75 (s, 1 H), 2.45 (s, 3 H), 2.12 (d, J = 7.7 Hz, 2 H), 1.66–1.54 (m, 2 H), 1.40 (s, 3 H), 1.38 (s, 3 H), 1.33–1.25 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.8, 134.5, 132.9, 129.8, 127.6, 118.4, 98.1, 75.8, 67.4, 59.3, 51.6, 36.4, 35.0, 28.9, 24.1, 23.4, 21.6, 21.1.

MS (EI): m/z = 390 (M⁺ – 1), 376, 304, 236, 178, 91.

HRMS (EI): m/z calcd for C₂₁H₂₉NO₄S (M⁺): 391.1817; found: 391.1815.

Ethyl {[3-(5-Allyl-2,2-dimethyl[1,3]dioxan-5-yl)propyl]-(p-toluenesulfonyl)amino}propynoate (31b)

According to the procedure for the synthesis of 11b, a solution of 28 (212.8 mg, 0.46 mmol), BuLi (0.65 mL, 1.01 mmol, 1.55 M hexane solution), and ethyl chlorocarbonate (0.05 mL, 0.55 mmol) in THF (9 mL) was stirred at –30 °C for 1 h to afford 31b (203.3 mg, 95%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 3:1).

IR (neat): 2218 (s), 1705 (s), 1598 (w), 1374 (s), 1175 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.82 (d, J = 8.2 Hz, 2 H), 7.37 (d, J = 8.2 Hz, 2 H), 5.67 (m, 1 H), 5.12–5.05 (m, 2 H), 4.22 (q, J = 7.2 Hz, 2 H), 3.55 (d, J = 11.6 Hz, 2 H), 3.48 (d, J = 11.6 Hz, 2 H), 3.40 (t, J = 7.0 Hz, 2 H), 2.46 (s, 3 H), 2.10 (d, J = 7.3 Hz, 2 H), 1.68–1.59 (m, 2 H), 1.39 (s, 3 H), 1.38 (s, 3 H), 1.30 (t, J = 7.2 Hz, 3 H), 1.30–1.24 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 154.1, 145.6, 134.2, 132.7, 130.1, 127.8, 118.5, 98.1, 82.1, 67.9, 67.4, 61.6, 51.8, 36.5, 35.0, 28.8, 23.8, 23.7, 21.7, 21.5, 14.2.

MS (EI): m/z = 462 (M⁺ – 1), 448, 308, 250, 220, 155, 91.

HRMS (EI): m/z calcd for C₂₄H₃₃NO₆S (M⁺): 463.2029; found: 463.2026.

N-Allyl-N-(3-hydroxypropyl)-p-toluenesulfonamide (34)

To a solution of 32 (1.81 g, 8.57 mmol), 33 (1.63 g, 8.57 mmol), and PPh₃ (2.81 g, 10.71 mmol) in THF (20 mL) was added DEAD (4.7 mL, 10.29 mmol) at 0 °C, and the mixture was stirred at r.t. for 2 h. The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 5:1) to provide N-allyl-N-[3-(tert-butyldimethylsilanyloxy)propyl]-p-toluenesulfonamide (2.10 g, 64%) as a pale yellow oil.

IR (neat): 1644 (w), 1599 (m), 1345 (s), 1162 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.70 (d, J = 8.3 Hz, 2 H), 7.29 (d, J = 8.3 Hz, 2 H), 5.65 (ddt, J = 10.2, 16.6, 6.3 Hz, 1 H), 5.20–5.10 (m, 2 H), 3.81 (d, J = 6.3 Hz, 2 H), 3.58 (dd, J = 5.9, 6.3 Hz, 2 H), 3.23–3.18 (m, 2 H), 2.42 (s, 3 H), 1.76–1.68 (m, 2 H), 0.87 (s, 9 H), 0.02 (s, 6 H).

¹³C NMR (100 MHz, CDCl₃): δ = 142.9, 136.9, 133.1, 129.4, 127.0, 118.5, 60.1, 50.7, 44.4, 31.4, 25.7, 21.3, 18.0, –5.6.

MS (EI): m/z = 382 (M⁺ – 1), 368, 326, 228, 91.

HRMS (EI): m/z calcd for C₁₉H₃₃NO₃SSi (M⁺): 383.1950; found: 383.1946.

To a solution of the above coupling product (665.1 mg, 1.73 mmol) in THF (3.5 mL) was added TBAF (5.2 mL, 5.20 mmol, 1 M THF solution) at 0 °C, and the resulting mixture was stirred at r.t. for 40 min. Sat. aq NH₄Cl was added, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine and dried (MgSO₄). The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 1:1) to provide 34 (463.5 mg, 99%) as a colorless oil.

IR (neat): 3534 (m), 1644 (w), 1598 (m), 1337 (s), 1159 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.70 (d, J = 8.2 Hz, 2 H), 7.31 (d, J = 8.2 Hz, 2 H), 5.62 (ddt, J = 10.1, 16.4, 6.3 Hz, 1 H), 5.20–5.11 (m, 2 H), 3.82 (d, J = 6.3 Hz, 2 H), 3.74 (dd, J = 5.3, 5.8 Hz, 2 H), 3.25 (dd, J = 6.3, 6.8 Hz, 2 H), 2.44 (s, 3 H), 2.35 (br, 1 H), 1.76–1.69 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 143.2, 136.3, 132.8, 129.6, 126.8, 118.8, 58.6, 50.8, 43.9, 30.6, 21.3.

MS (EI): m/z = 269 (M⁺), 224 155, 114, 91.

HRMS (EI): m/z calcd for C₁₃H₁₉NO₃S (M⁺): 269.1086; found: 269.1104.

N-[3-(N-Allyl-N-p-toluenesulfonyl)aminopropyl]-N-tert-butoxycarbonyl-p-toluenesulfonamide (36)

To a solution of 34 (304.5 mg, 1.13 mmol), 35 (337.4 mg, 1.24 mmol), and PPh₃ (370.6 mg, 1.41 mmol) in THF (6 mL) was added DEAD (0.62 mL, 1.36 mmol) at 0 °C, and the mixture was stirred at r.t. for 20 min. The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 3:1) to provide 36 (590.9 mg, quant) as a colorless oil.

IR (neat): 1728 (s), 1644 (w), 1598 (m), 1350 (s), 1157 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.77 (d, J = 8.2 Hz, 2 H), 7.70 (d, J = 8.2 Hz, 2 H), 7.33–7.28 (m, 4 H), 5.63 (ddt, J = 10.1, 16.9, 6.3 Hz, 1 H), 5.20 (d, J = 16.9 Hz, 1 H), 5.15 (d, J = 10.1 Hz, 1 H), 3.85 (d, J = 6.3 Hz, 2 H), 3.83 (t, J = 7.2 Hz, 2 H), 3.22 (t, J = 7.2 Hz, 2 H), 2.44 (s, 3 H), 2.42 (s, 3 H), 2.05–1.96 (m, 2 H), 1.34 (s, 9 H).

¹³C NMR (100 MHz, CDCl₃): δ = 150.7, 144.1, 143.2, 137.1, 136.7, 132.7, 129.6, 129.2, 127.6, 127.0, 119.2, 84.2, 50.4, 44.8, 44.6, 28.6, 27.7, 21.5, 21.4.

MS (EI): m/z = 522 (M⁺), 465, 449, 421, 267, 224, 155, 91.

HRMS (EI): m/z calcd for C₂₅H₃₄N₂O₆S₂ (M⁺): 522.1858; found: 522.1843.

N-[2-(N-Allyl-N-p-toluenesulfonyl)aminobenzyl]-N-tert-butoxycarbonyl-p-toluenesulfonamide (39)

To a solution of 38 (2.97 g, 9.36 mmol), 35 (2.79 g, 10.29 mmol), and PPh₃ (3.07 mg, 11.70 mmol) in THF (50 mL) was added DEAD (5.1 mL, 11.23 mmol) at 0 °C, and the mixture was stirred at r.t. for 0.5 h. The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 4:1) to provide 39 (4.50 g, 84%) as a white solid; mp 65 °C.

IR (KBr): 1732 (s), 1598 (w), 1354 (s), 1167 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.80 (d, J = 8.2 Hz, 2 H), 7.56 (d, J = 8.2 Hz, 2 H), 7.40 (d, J = 7.2 Hz, 1 H), 7.34–7.28 (m, 5 H), 7.10 (ddd, J = 1.0, 7.2, 7.7 Hz, 1 H), 6.49 (dd, J = 1.0, 7.2 Hz, 1 H), 5.87 (m, 1 H), 5.42 (d, J = 17.6 Hz, 1 H), 5.26 (d, J = 17.6 Hz, 1 H), 5.07–5.01 (m, 2 H), 4.43 (dd, J = 5.8, 14.0 Hz, 1 H), 3.91 (dd, J = 7.7, 14.0 Hz, 1 H), 2.46 (s, 6 H), 1.35 (s, 9 H).

¹³C NMR (100 MHz, CDCl₃): δ = 151.1, 144.2, 143.7, 139.5, 137.1, 136.6, 135.1, 132.4, 129.5, 129.2, 128.7, 128.2, 128.1, 127.8, 127.0, 126.9, 119.6, 84.3, 54.9, 47.9, 27.8, 21.6, 21.6.

MS (EI): m/z = 570 (M⁺), 497, 415, 315, 144, 91.

HRMS (EI): m/z calcd for C₂₉H₃₄N₂O₆S₂ (M⁺): 570.1858; found: 570.1854.

N-Allyl-N-[3-(N-p-toluenesulfonyl)aminopropyl]-p-toluenesulfonamide (40)

To a solution of 36 (590.9 mg, 1.13 mmol) in CH₂Cl₂ (5 mL) was added TFA (1 mL) at 0 °C, and the mixture was stirred at r.t. for 1 h. The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 2:1) to provide 40 (477.7 mg, quant) as a colorless oil.

IR (neat): 3283 (m), 1644 (w), 1598 (m), 1331 (s), 1159 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.76 (d, J = 8.2 Hz, 2 H), 7.67 (d, J = 8.2 Hz, 2 H), 7.34–7.29 (m, 4 H), 5.53 (ddt, J = 10.1, 16.9, 6.8 Hz, 1 H), 5.21 (t, J = 6.8 Hz, 1 H), 5.16–5.08 (m, 2 H), 3.73 (d, J = 6.8 Hz, 2 H), 3.15 (t, J = 6.3 Hz, 2 H), 3.04 (ddd, J = 5.3, 6.8, 6.8 Hz, 2 H), 2.44 (s, 3 H), 2.43 (s, 3 H), 1.76–1.68 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 143.2, 142.9, 136.7, 135.9, 132.4, 129.5, 129.4, 126.7, 126.6, 118.9, 50.7, 44.2, 39.6, 27.8, 21.1, 21.1.

MS (EI): m/z = 422 (M⁺), 267, 224, 155, 91.

HRMS (EI): m/z calcd for C₂₀H₂₆N₂O₄S₂ (M⁺): 422.1334; found: 422.1316.

N-Allyl-N-[2-(N-p-toluenesulfonyl)aminomethylphenyl]-p-toluenesulfonamide (41)

To a solution of 39 (4.43 g, 7.76 mmol) in CH₂Cl₂ (40 mL) was added TFA (8 mL) at 0 °C, and the mixture was stirred at r.t. for 1 h. The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 2:1) to provide 41 (3.65 g, quant) as a white solid; mp 121 °C.

IR (KBr): 1597 (w), 1344 (s), 1160 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.83 (d, J = 8.2 Hz, 2 H), 7.53 (d, J = 7.7 Hz, 1 H), 7.47 (d, J = 8.2 Hz, 2 H), 7.35 (d, J = 8.7 Hz, 2 H), 7.31–7.25 (m, 3 H), 7.09 (dt, J = 1.0, 7.7 Hz, 1 H), 6.35 (d, J = 7.7 Hz, 1 H), 5.63 (dd, J = 3.9, 8.7 Hz, 1 H), 5.50 (dddd, J = 5.8, 8.2, 10.2, 16.9 Hz, 1 H), 4.95 (d, J = 10.2 Hz, 1 H), 4.88 (d, J = 16.9 Hz, 1 H), 4.39 (dd, J = 5.8, 14.0 Hz, 1 H), 4.23–4.15 (m, 2 H), 3.58 (dd, J = 8.2, 14.0 Hz, 1 H), 2.46 (s, 3 H), 2.45 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.1, 143.2, 138.1, 137.5, 137.0, 134.3, 131.7, 131.6, 129.7, 129.6, 129.0, 128.4, 128.1, 127.4, 127.2, 120.1, 55.0, 43.0, 21.6, 21.5.

MS (EI): m/z = 470 (M⁺), 315, 144, 91.

HRMS (EI): m/z calcd for C₂₄H₂₆N₂O₄S₂ (M⁺): 470.1334; found: 470.1329.

N-[3-(N-Allyl-N-p-toluenesulfonyl)aminopropyl]-N-formyl-p-toluenesulfonamide (42)

According to the procedure for the synthesis of 5, a solution of 40 (2.04 g, 4.84 mmol), BuLi (3.6 mL, 5.80 mmol, 1.63 M hexane solution), and 1-formylbenzotriazole (1.42 g, 9.67 mmol) in THF (25 mL) was stirred at –50 °C for 0.5 h to afford 42 (2.01 g, 92%) as a colorless oil after purification by column chromatography on silica gel (hexane/EtOAc 3:1).

IR (neat): 1699 (s), 1643 (w), 1597 (m), 1357 (s), 1165 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 9.07 (s, 1 H), 7.75 (d, J = 8.2 Hz, 2 H), 7.66 (d, J = 8.2 Hz, 2 H), 7.38 (d, J = 8.2 Hz, 2 H), 7.29 (d, J = 8.2 Hz, 2 H), 5.55 (ddt, J = 10.1, 16.9, 6.8 Hz, 1 H), 5.19–5.09 (m, 2 H), 3.79 (d, J = 6.8 Hz, 2 H), 3.49–3.43 (m, 2 H), 3.13 (t, J = 6.8 Hz, 2 H), 2.45 (s, 3 H), 2.41 (s, 3 H), 1.85–1.75 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 161.1, 145.5, 143.3, 136.5, 134.5, 132.5, 130.3, 129.6, 127.3, 127.0, 119.3, 50.3, 44.5, 40.2, 26.5, 21.5, 21.4.

MS (EI): m/z = 450 (M⁺), 295, 224, 155, 91.

HRMS (EI): m/z calcd for C₂₁H₂₆N₂O₅S₂ (M⁺): 450.1283; found: 450.1287.

N-[2-(N-Allyl-N-p-toluenesulfonyl)aminobenzyl]-N-formyl-p-toluenesulfonamide (43)

According to the procedure for the synthesis of 5, a solution of 41 (3.55 g, 7.65 mmol), BuLi (5.8 mL, 9.05 mmol, 1.55 M hexane solution), and 1-formylbenzotriazole (2.22 g, 15.09 mmol) in THF (40 mL) was stirred at –30 °C for 1 h to afford 43 (3.12 g, 83%) as a white solid after purification by column chromatography on silica gel (hexane/EtOAc 4:1); mp 63 °C.

IR (KBr): 1702 (s), 1598 (w), 1349 (s), 1166 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 9.24 (s, 1 H), 7.77 (d, J = 8.2 Hz, 2 H), 7.50 (d, J = 8.2 Hz, 2 H), 7.36 (d, J = 8.2 Hz, 2 H), 7.28 (d, J = 8.2 Hz, 2 H), 7.17–7.26 (m, 2 H), 7.05 (ddd, J = 1.9, 6.8, 8.2 Hz, 1 H), 6.41 (d, J = 7.7 Hz, 1 H), 5.85 (dddd, J = 6.3, 7.7, 10.2, 16.9 Hz, 1 H), 5.02–5.10 (m, 2 H), 5.00 (d, J = 16.9 Hz, 1 H), 4.93 (d, J = 16.9 Hz, 1 H), 4.45 (dd, J = 6.3, 14.0 Hz, 1 H), 3.83 (dd, J = 7.7, 14.0 Hz, 1 H), 2.46 (s, 3 H), 2.45 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 161.5, 145.6, 143.9, 137.0, 136.9, 134.8, 134.4, 132.3, 130.3, 129.4, 128.5, 128.2, 127.5, 127.4, 127.3, 127.2, 119.7, 54.8, 42.6, 21.6, 21.6.

MS (EI): m/z = 498 (M⁺), 343, 315, 159, 144, 91.

HRMS (EI): m/z calcd for C₂₅H₂₆N₂O₅S₂ (M⁺): 498.1283; found: 498.1273.

N-[3-(N-Allyl-N-p-toluenesulfonyl)aminopropyl]-N-(2,2-dichloroethenyl)-p-toluenesulfonamide (44)

According to the procedure for the synthesis of 8, a solution of 42 (2.01 g, 4.45 mmol), PPh₃ (2.92 g, 11.13 mmol), and CCl₄ (3.5 mL, 36.51 mmol) in THF (15 mL) was stirred at 60 °C for 4.5 h to afford 44 (2.24 g, 97%) as a colorless oil after purification by silica gel column chromatography (hexane/EtOAc 3:1).

IR (neat): 1598 (m), 1345 (s), 1165 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.70–7.65 (m, 2 H), 7.36–7.29 (m, 4 H), 6.20 (s, 1 H), 5.60 (ddt, J = 10.1, 16.9, 6.8 Hz, 1 H), 5.22–5.13 (m, 2 H), 3.79 (d, J = 6.8 Hz, 2 H), 3.33 (t, J = 7.3 Hz, 2 H), 3.15 (t, J = 7.2 Hz, 2 H), 2.45 (s, 3 H), 2.43 (s, 3 H), 1.85–1.76 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.0, 143.0, 136.1, 134.4, 132.7, 129.6, 129.4, 126.9, 126.7, 124.8, 124.5, 118.7, 50.8, 46.6, 44.7, 27.0, 21.1, 21.1.

MS (EI): m/z = 516 (M⁺), 481, 393, 361, 224, 155, 91.

HRMS (EI): m/z calcd for C₂₂H₂₆ ³⁵Cl₂N₂O₄S₂ (M⁺): 516.0711; found: 516.0704.

N-[2-(N-Allyl-N-p-toluenesulfonyl)aminobenzyl]-N-(2,2-dichlorovinyl)-p-toluenesulfonamide (45)

According to the procedure for the synthesis of 8, a solution of 43 (2.93 g, 5.88 mmol), PPh₃ (3.85 g, 14.69 mmol), and CCl₄ (4.6 mL, 48.19 mmol) in THF (20 mL) was stirred at 60 °C for 4 h to afford 45 (3.27 g, 98%) as a white solid after purification by column chromatography on silica gel (hexane/EtOAc 4:1); mp 137 °C.

IR (KBr): 1736 (w), 1598 (m), 1351 (s), 1166 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.72–7.78 (m, 3 H), 7.46 (d, J = 8.2 Hz, 2 H), 7.38 (d, J = 8.2 Hz, 2 H), 7.33 (ddd, J = 1.0, 7.2, 7.7 Hz, 1 H), 7.27 (d, J = 8.2 Hz, 2 H), 7.10 (ddd, J = 1.4, 7.7, 7.7 Hz, 1 H), 6.40 (dd, J = 1.0, 8.2 Hz, 1 H), 6.22 (s, 1 H), 5.63 (dddd, J = 5.8, 7.7, 10.1, 16.9 Hz, 1 H), 5.03 (dd, J = 1.5, 10.1 Hz, 1 H), 4.96 (dd, J = 1.5, 16.9 Hz, 1 H), 4.82 (d, J = 16.4 Hz, 1 H), 4.70 (d, J = 16.4 Hz, 1 H), 4.41 (dd, J = 5.8, 13.5 Hz, 1 H), 3.69 (dd, J = 7.7, 13.5 Hz, 1 H), 2.48 (s, 3 H), 2.45 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.3, 143.9, 138.0, 137.0, 135.3, 134.4, 131.7, 130.0, 129.5, 129.5, 128.6, 128.1, 127.7, 127.4, 127.1, 126.5, 125.7, 120.1, 54.8, 49.5, 21.6, 21.6.

MS (EI): m/z = 564 (M⁺), 529, 441, 409, 300, 144, 91.

HRMS (EI): m/z calcd for C₂₆H₂₆ ³⁵Cl₂N₂O₄S₂ (M⁺): 564.0711; found: 564.0712.

N-[3-(N-Allyl-N-p-toluenesulfonyl)aminopropyl]-N-ethynyl-p-toluenesulfonamide (46a)

According to the procedure for the synthesis of 11a, a solution of 44 (269.6 mg, 0.52 mmol) and BuLi (0.70 mL, 1.15 mmol, 1.63 M hexane solution) in THF (10 mL) was stirred at –78 °C for 10 min to afford 46a (176.2 mg, 76%) as a colorless oil after purification by column chromatography on silica gel (hexane/EtOAc 3:1).

IR (neat): 2134 (m), 1644 (w), 1598 (m), 1364 (s), 1167 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.79 (d, J = 8.2 Hz, 2 H), 7.68 (d, J = 8.2 Hz, 2 H), 7.36 (d, J = 8.2 Hz, 2 H), 7.31 (d, J = 8.2 Hz, 2 H), 5.60 (ddt, J = 10.1, 16.4, 6.3 Hz, 1 H), 5.22–5.12 (m, 2 H), 3.77 (d, J = 6.3 Hz, 2 H), 3.32 (dd, J = 6.8, 7.3 Hz, 2 H), 3.14 (dd, J = 6.8, 7.7 Hz, 2 H), 2.73 (s, 1 H), 2.46 (s, 3 H), 2.43 (s, 3 H), 1.99–1.91 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.8, 143.2, 136.2, 133.8, 132.5, 129.7, 129.6, 127.4, 126.9, 119.2, 75.4, 59.3, 51.0, 48.7, 44.5, 26.6, 21.4, 21.3.

MS (EI): m/z = 445 (M⁺ – 1), 381, 317, 291, 224, 155, 135, 91.

HRMS (EI): m/z calcd for C₂₂H₂₆N₂O₄S₂ (M⁺): 446.1334; found: 446.1353.

Ethyl {[3-(Allyl-p-toluenesulfonylamino)propyl]-(p-toluenesulfonyl)amino}propynoate (46b)

According to the procedure for the synthesis of 11b, a solution of 44 (508.8 mg, 0.98 mmol), BuLi (1.3 mL, 2.16 mmol, 1.63 M hexane solution), and ethyl chlorocarbonate (0.11 mL, 1.18 mmol) in THF (20 mL) was stirred at –20 °C for 2 h to afford 46b (415.2 mg, 81%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 2:1).

IR (neat): 2219 (s), 1705 (s), 1598 (w), 1372 (s), 1174 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.81 (d, J = 8.2 Hz, 2 H), 7.67 (d, J = 8.2 Hz, 2 H), 7.38 (d, J = 7.7 Hz, 2 H), 7.31 (d, J = 7.7 Hz, 2 H), 5.60 (ddt, J = 9.7, 16.4, 6.7 Hz, 1 H), 5.22–5.12 (m, 2 H), 4.23 (q, J = 7.3 Hz, 2 H), 3.76 (d, J = 6.7 Hz, 2 H), 3.45 (dd, J = 6.8, 7.7 Hz, 2 H), 3.13 (dd, J = 6.8, 7.3 Hz, 2 H), 2.47 (s, 3 H), 2.43 (s, 3 H), 2.00–1.91 (m, 2 H), 1.31 (t, J = 7.3 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 153.8, 145.6, 143.4, 136.2, 133.7, 132.6, 130.1, 129.7, 127.6, 127.0, 119.4, 81.8, 67.7, 61.5, 51.2, 49.0, 44.5, 26.9, 21.6, 21.4, 14.0.

MS (EI): m/z = 518 (M⁺), 473, 454, 363, 339, 317, 299, 267, 252, 224, 207, 155.

HRMS (EI): m/z calcd for C₂₅H₃₀N₂O₆S₂ (M⁺): 518.1545; found: 518.1538.

N-[2-(N-Allyl-N-p-toluenesulfonyl)aminobenzyl]-N-ethynyl-p-toluenesulfonamide (47a)

According to the procedure for the synthesis of 11a, a solution of 45 (303.8 mg, 0.54 mmol) and BuLi (0.76 mL, 1.18 mmol, 1.55 M hexane solution) in THF (10 mL) was stirred at –78 °C for 0.5 h to afford 47a (208.4 mg, 78%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 3:1).

IR (neat): 2136 (s), 1645 (w), 1597 (s), 1348 (s), 1171 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.84 (d, J = 8.7 Hz, 2 H), 7.62 (d, J = 6.8 Hz, 1 H), 7.48 (d, J = 8.2 Hz, 2 H), 7.39 (d, J = 8.2 Hz, 2 H), 7.34–7.26 (m, 3 H), 7.12 (dt, J = 1.5, 7.7 Hz, 1 H), 6.46 (dd, J = 1.0, 8.2 Hz, 1 H), 5.71 (dddd, J = 5.8, 7.7, 10.6, 16.4 Hz, 1 H), 5.01–4.94 (m, 2 H), 4.86 (d, J = 15.9 Hz, 1 H), 4.72 (d, J = 15.9 Hz, 1 H), 4.38 (dd, J = 5.8, 14.0 Hz, 1 H), 3.77 (dd, J = 7.7, 14.0 Hz, 1 H), 2.63 (s, 1 H), 2.49 (s, 3 H), 2.45 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.9, 143.9, 137.1, 137.0, 134.6, 134.5, 131.9, 129.9, 129.5, 129.1, 128.7, 128.1, 127.9, 127.8, 127.5, 119.9, 60.4, 58.8, 54.8, 51.5, 21.7, 21.6.

MS (EI): m/z = 494 (M⁺), 339, 183, 144, 91.

HRMS (EI): m/z calcd for C₂₆H₂₆N₂O₄S₂ (M⁺): 494.1334; found: 494.1321.

Ethyl {[2-(Allyl-p-toluenesulfonylamino)benzyl](p-toluenesulfonyl)amino}propynoate (47b)

According to the procedure for the synthesis of 11b, a solution of 45 (382.3 mg, 0.68 mmol), BuLi (0.96 mL, 1.49 mmol, 1.55 M hexane solution), and ethyl chlorocarbonate (0.08 mL, 0.81 mmol) in THF (10 mL) was stirred at –30 °C for 1 h to afford 47b (318.8 mg, 83%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 3:1).

IR (neat): 2220 (s), 1706 (s), 1598 (m), 1348 (s), 1172 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.86 (d, J = 8.2 Hz, 2 H), 7.53 (d, J = 8.2 Hz, 1 H), 7.47 (d, J = 8.2 Hz, 2 H), 7.40 (d, J = 7.7 Hz, 2 H), 7.34–7.26 (m, 3 H), 7.13 (dt, J = 1.5, 7.7 Hz, 1 H), 6.45 (dd, J = 1.0, 8.2 Hz, 1 H), 5.73 (dddd, J = 5.8, 7.7, 10.2, 16.9 Hz, 1 H), 5.09–4.96 (m, 3 H), 4.81 (d, J = 15.9 Hz, 1 H), 4.41 (dd, J = 5.8, 13.5 Hz, 1 H), 4.16 (q, J = 7.2 Hz, 2 H), 3.76 (dd, J = 7.7, 13.5 Hz, 1 H), 2.49 (s, 3 H), 2.45 (s, 3 H), 1.25 (t, J = 7.2 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 153.9, 145.6, 144.0, 137.2, 136.4, 134.4, 134.1, 131.7, 130.2, 129.5, 129.0, 128.8, 128.2, 128.1, 127.9, 127.5, 120.4, 83.1, 67.3, 61.4, 54.7, 51.5, 21.7, 21.6, 14.1.

MS (EI): m/z = 566 (M⁺), 521, 411, 365, 255, 144, 91.

HRMS (EI): m/z calcd for C₂₉H₃₀N₂O₆S₂ (M⁺): 566.1545; found: 566.1533.

N-[2-(N-Allyl-N-p-toluenesulfonyl)aminobenzyl]-N-(2-trimethylsilylethynyl)-p-toluenesulfonamide (47c)

According to the procedure for the synthesis of 21d, a solution of 41 (511.7 mg, 1.09 mmol), BuLi (0.80 mL, 1.20 mmol, 1.55 M hexane solution), and phenyl(trimethylsilylethynyl)iodonium triflate (587.5 mg, 1.30 mmol) in toluene (10 mL) was stirred at r.t. for 18 h to afford 47c (452.1 mg, 73%) as a pale brownish solid after purification by column chromatography on silica gel (hexane/EtOAc 3:1); mp 105 °C.

IR (KBr): 2173 (s), 1647 (w), 1597 (m), 1368 (s), 1165 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.81 (d, J = 8.2 Hz, 2 H), 7.60 (dd, J = 1.0, 7.7 Hz, 1 H), 7.49 (d, J = 8.2 Hz, 2 H), 7.37 (d, J = 8.2 Hz, 2 H), 7.32–7.26 (m, 3 H), 7.12 (dt, J = 1.0, 7.7 Hz, 1 H), 6.46 (dd, J = 1.0, 8.2 Hz, 1 H), 5.70 (m, 1 H), 5.01–4.95 (m, 2 H), 4.87 (d, J = 15.7 Hz, 1 H), 4.65 (d, J = 15.7 Hz, 1 H), 4.35 (dd, J = 5.8, 14.0 Hz, 1 H), 3.82 (dd, J = 7.7, 14.0 Hz, 1 H), 2.48 (s, 3 H), 2.45 (s, 3 H), 0.08 (s, 9 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.7, 143.8, 137.2, 137.1, 134.7, 134.4, 132.1, 129.7, 129.5, 129.5, 128.6, 128.1, 127.9, 127.8, 127.6, 119.7, 96.1, 72.8, 54.8, 51.8, 21.7, 21.6, –0.0.

MS (EI): m/z = 566 (M⁺), 551, 411, 255, 144, 91.

HRMS (EI): m/z calcd for C₂₉H₃₄N₂O₄S₂Si₂ (M⁺): 566.1729; found: 566.1717.

Metathesis Reaction of 11a; 1-(p-Toluenesulfonyl)-2-vinyl-1,4-dihydroquinoline (48a); Typical Procedure (Table [1], entry 1)

To a solution of the ruthenium carbene complex 1b (17.2 mg, 20.22 μmol, 5 mol%) in toluene (15 mL) was added 11a (125.9 mg, 0.40 mmol) in toluene (5 mL) at 0 °C, and the solution was stirred at 80 °C for 0.5 h under an ethylene atmosphere. A few drops of ethyl vinyl ether was added to the mixture, and the volatiles were removed under reduced pressure. The residue was purified by column chromatography on silica gel (hexane/EtOAc 10:1) to afford 48a (116.8 mg, 93%) as a pale yellow oil.

IR (neat): 1597 (w), 1354 (s), 1172 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.74 (dd, J = 1.0, 8.2 Hz, 1 H), 7.30 (ddd, J = 1.0, 7.3, 8.2 Hz, 1 H), 7.25 (d, J = 8.2 Hz, 2 H), 7.18 (ddd, J = 1.0, 7.3, 7.7 Hz, 1 H), 7.10 (d, J = 8.2 Hz, 2 H), 6.87 (dd, J = 1.0, 7.7 Hz, 1 H), 6.46 (dd, J = 10.6, 17.4 Hz, 1 H), 5.91 (t, J = 4.8 Hz, 1 H), 5.78 (d, J = 17.4 Hz, 1 H), 5.26 (d, J = 10.6 Hz, 1 H), 2.38 (s, 3 H), 2.43–2.02 (br, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 144.0, 140.1, 137.5, 134.7, 133.8, 133.8, 129.2, 128.0, 127.8, 127.2, 126.9, 126.6, 123.2, 115.5, 27.6, 21.6.

MS (EI): m/z = 311 (M⁺), 156, 128.

HRMS (EI): m/z calcd for C₁₈H₁₇NO₂S (M⁺): 311.0980; found: 311.0981.

Ethyl 2-[1-(p-Toluenesulfonyl)-1,4-dihydroquinolin-2-yl]acrylate (48b)

According to the typical procedure for the metathesis reaction of 11a, a solution of 11b (40.3 mg, 0.11 mmol) and 1b (4.5 mg, 5.25 μmol) in toluene (5.5 mL) was stirred at 80 °C for 1 h under an argon atmosphere to afford 48b (31.8 mg, 79%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 10:1).

IR (neat): 1719 (s), 1597 (w), 1351 (m), 1170 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.74 (d, J = 7.7 Hz, 1 H), 7.34–7.28 (m, 3 H), 7.19 (dd, J = 7.2, 7.7 Hz, 1 H), 7.14 (d, J = 7.7 Hz, 2 H), 6.89 (d, J = 7.3 Hz, 1 H), 6.31 (s, 1 H), 6.12 (s, 1 H), 6.11 (t, J = 4.8 Hz, 1 H), 4.29 (q, J = 7.3 Hz, 2 H), 2.39 (s, 3 H), 2.29 (br, 2 H), 1.34 (t, J = 7.3 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 165.7, 144.1, 138.5, 137.3, 136.7, 134.1, 133.9, 129.2, 127.9, 127.4, 127.2, 127.0, 126.7, 125.9, 125.4, 61.0, 27.7, 21.6, 14.2.

MS (EI): m/z = 383 (M⁺), 338, 318, 228, 182, 154, 128, 91.

HRMS (EI): m/z calcd for C₂₁H₂₁NO₄S (M⁺): 383.1191; found: 383.1194.

Dimethyl 10-(p-Toluenesulfonyl)-3,9,9a,10-tetrahydroacridine-1,2-dicarboxylate (49)

To a solution of 48a (30.6 mg, 0.10 mmol) in toluene (5 mL) was added DMAD (0.06 mL, 0.49 mmol), and the solution was stirred at 80 °C for 12 h. The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 2:1) to provide 49 (19.9 mg, 45%) as a pale yellow oil.

IR (neat): 1728 (s), 1361 (m), 1171 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.87 (d, J = 8.3 Hz, 1 H), 7.45 (d, J = 8.3 Hz, 2 H), 7.27–7.18 (m, 3 H), 7.10 (dd, J = 7.3, 7.8 Hz, 1 H), 6.96 (d, J = 7.8 Hz, 1 H), 6.17 (m, 1 H), 3.79 (s, 3 H), 3.75 (s, 3 H), 3.32–3.15 (m, 2 H), 2.80 (dd, J = 5.9, 15.6 Hz, 1 H), 2.67 (m, 1 H), 2.39 (s, 3 H), 2.37 (m, 1 H).

¹³C NMR (100 MHz, CDCl₃): δ = 167.5, 167.0, 144.2, 137.0, 136.7, 135.4, 132.2, 129.8, 129.6, 129.0, 127.6, 127.6, 127.0, 125.4, 124.9, 121.4, 52.4, 52.3, 33.6, 33.1, 28.2, 21.5.

MS (EI): m/z = 453 (M⁺), 422, 389, 330, 266, 238, 194, 179.

HRMS (EI): m/z calcd for C₂₄H₂₃NO₆S (M⁺): 453.1246; found: 453.1263.

2-(p-Toluenesulfonyl)-3-vinyl-1,2-dihydroisoquinoline (50a)

According to the typical procedure for the metathesis reaction of 11a, a solution of 12a (48.9 mg, 0.16 mmol) and 1b (6.7 mg, 7.85 μmol) in toluene (8.0 mL) was stirred at 80 °C for 0.5 h under an ethylene atmosphere to afford 50a (34.4 mg, 70%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 10:1).

IR (neat): 1598 (w), 1349 (s), 1164 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.30 (d, J = 8.2 Hz, 2 H), 7.04 (ddd, J = 1.0, 7.0, 7.2 Hz, 1 H), 6.99–6.92 (m, 2 H), 6.83 (d, J = 8.2 Hz, 2 H), 6.68 (d, J = 7.2 Hz, 1 H), 6.54 (dd, J = 11.1, 17.4 Hz, 1 H), 6.44 (s, 1 H), 5.84 (d, J = 17.4 Hz, 1 H), 5.37 (d, J = 11.1 Hz, 1 H), 4.75 (s, 2 H), 2.18 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 143.1, 138.4, 134.3, 133.9, 131.1, 130.0, 128.3, 127.8, 127.5, 127.2, 125.2, 124.9, 120.4, 117.3, 50.4, 21.2.

MS (EI): m/z = 311 (M⁺), 156, 128.

HRMS (EI): m/z calcd for C₁₈H₁₇NO₂S (M⁺): 311.0980; found: 311.0979.

Ethyl 2-[2-(p-Toluenesulfonyl)-1,2-dihydroisoquinolin-3-yl]acrylate (50b)

According to the typical procedure for the metathesis reaction of 11a, a solution of 12b (45.4 mg, 0.12 mmol) and 1b (5.0 mg, 5.92 µmol) in toluene (6.0 mL) was stirred at 80 °C for 1 h under an ethylene atmosphere to afford 50b (35.2 mg, 78%) as a pale yellow oil after purification by column chromatography on silica gel (benzene/EtOAc 30:1).

IR (neat): 1721 (s), 1352 (s), 1165 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.33 (d, J = 8.5 Hz, 2 H), 7.09 (dd, J = 7.2, 7.7 Hz, 1 H), 7.03–6.98 (m, 2 H), 6.87 (d, J = 8.5 Hz, 2 H), 6.76 (d, J = 7.7 Hz, 1 H), 6.58 (s, 1 H), 6.34 (d, J = 1.0 Hz, 1 H), 6.08 (d, J = 1.0 Hz, 1 H), 4.85 (s, 2 H), 4.32 (q, J = 7.2 Hz, 2 H), 2.19 (s, 3 H), 1.37 (t, J = 7.2 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 165.6, 143.1, 138.9, 135.5, 134.6, 130.7, 130.0, 128.4, 128.2, 127.3, 127.3, 127.0, 125.2, 125.1, 122.9, 61.1, 50.1, 21.3, 14.1.

MS (EI): m/z = 383 (M⁺), 228, 182, 154, 128.

HRMS (EI): m/z calcd for C₂₁H₂₁NO₄S (M⁺): 383.1191; found: 383.1194.

3-(1-Phenylvinyl)-2-(p-toluenesulfonyl)-1,2-dihydroisoquinoline (50c)

According to the typical procedure for the metathesis reaction of 11a, a solution of 12c (40.2 mg, 0.10 mmol) and 1b (4.4 mg, 5.19 μmol) in toluene (5.0 mL) was stirred at 80 °C for 1.5 h under an ethylene atmosphere to afford 50c (30.8 mg, 77%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 10:1).

IR (neat): 1598 (w), 1354 (s), 1166 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.47–7.28 (m, 7 H), 7.07 (ddd, J = 1.0, 7.3, 7.8 Hz, 1 H), 7.02–6.95 (m, 2 H), 6.89 (d, J = 8.3 Hz, 2 H), 6.73 (d, J = 7.3 Hz, 1 H), 6.41 (s, 1 H), 5.75 (d, J = 1.0 Hz, 1 H), 5.47 (d, J = 1.0 Hz, 1 H), 4.80 (s, 2 H), 2.21 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 147.1, 143.1, 140.0, 140.0, 135.3, 131.2, 130.3, 128.4, 128.2, 128.1, 128.0, 127.8, 127.5, 127.3, 125.2, 125.1, 122.6, 117.5, 50.5, 21.3.

MS (EI): m/z = 387 (M⁺), 230, 217, 202, 154, 117, 91.

HRMS (EI): m/z calcd for C₂₄H₂₁NO₂S (M⁺): 387.1293; found: 387.1293.

Dimethyl 5-(p-Toluenesulfonyl)-3,4,5,6-tetrahydrophenanthridine-1,2-dicarboxylate (51)

To a solution of 50a (48.2 mg, 0.15 mmol) in toluene (3 mL) was added DMAD (0.06 mL, 0.46 mmol) at r.t., and the mixture was stirred at 80 °C for 21 h. The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc, 2:1) to provide 51 (34.8 mg, 50%) as a pale yellow oil.

IR (neat): 1732 (s), 1354 (m), 1165 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.29 (d, J = 8.4 Hz, 2 H), 7.07 (ddd, J = 1.0, 6.8, 7.3 Hz, 1 H), 7.02–6.97 (m, 2 H), 6.88 (d, J = 8.4 Hz, 2 H), 6.81 (d, J = 7.3 Hz, 1 H), 4.72 (s, 2 H), 3.80 (s, 3 H), 3.66 (s, 3 H), 3.00 (t, J = 8.9 Hz, 2 H), 2.61 (t, J = 8.9 Hz, 2 H), 2.22 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 168.3, 166.7, 143.7, 142.0, 136.8, 135.1, 130.2, 129.5, 128.8, 127.4, 127.4, 126.7, 126.6, 125.6, 123.4, 122.1, 52.3, 52.3, 50.8, 27.0, 23.9, 21.3.

MS (EI): m/z = 453 (M⁺), 422, 298, 266, 238, 180.

HRMS (EI): m/z calcd for C₂₄H₂₃NO₆S (M⁺): 453.1246; found: 453.1244.

Dimethyl 5-(p-Toluenesulfonyl)-3,5,6,10b-tetrahydrophenanthridine-1,2-dicarboxylate (52)

According to the typical procedure for the metathesis reaction of 11a, a solution of 12a (43.5 mg, 0.14 mmol) and 1b (5.9 mg, 6.98 μmol) in toluene (7.0 mL) was stirred at 80 °C for 0.5 h under an ethylene atmosphere. After cooling to r.t., DMAD (0.09 mL, 0.70 mmol) was added and the mixture was stirred at 80 °C for 12 h under an argon atmosphere. The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 2:1) to provide 52 (29.1 mg, 46%) as a pale yellow oil.

IR (neat): 1732 (s), 1354 (m), 1168 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.71 (d, J = 8.2 Hz, 2 H), 7.31 (d, J = 8.2 Hz, 2 H), 7.24–7.21 (m, 3 H), 6.93 (m, 1 H), 5.93 (t, J = 3.6 Hz, 1 H), 4.89 (d, J = 13.8 Hz, 1 H), 4.34 (d, J = 13.8 Hz, 1 H), 3.86 (s, 3 H), 3.77 (t, J = 6.3 Hz, 1 H), 3.69 (s, 3 H), 3.22–3.16 (m, 2 H), 2.42 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 168.8, 166.6, 144.2, 138.9, 138.6, 134.8, 132.1, 131.6, 129.8, 128.3, 127.7, 127.4, 126.9, 126.9, 123.3, 110.7, 52.5, 52.4, 49.5, 39.2, 29.5, 21.6.

MS (EI): m/z = 453 (M⁺), 422, 389, 330, 298, 266, 238, 180.

HRMS (EI): m/z calcd for C₂₄H₂₃NO₆S (M⁺): 453.1246; found: 453.1244.

2-(p-Toluenesulfonyl)-3-vinyl-2,5-dihydro-1H-benzo[c]azepine (53a)

According to the typical procedure for the metathesis reaction of 11a, a solution of 13a (33.4 mg, 0.10 mmol) and 1b (4.4 mg, 5.13 μmol) in toluene (5.1 mL) was stirred at 80 °C for 0.5 h under an argon atmosphere to afford 53a (16.2 mg, 49%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 10:1).

IR (neat): 1597 (w), 1338 (s), 1159 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.27 (d, J = 8.2 Hz, 2 H), 7.19–7.11 (m, 2 H), 7.06 (ddd, J = 1.9, 7.3, 7.3 Hz, 1 H), 6.97 (d, J = 8.2 Hz, 2 H), 6.73 (d, J = 7.7 Hz, 1 H), 6.38 (dd, J = 10.6, 16.9 Hz, 1 H), 5.77 (t, J = 5.8 Hz, 1 H), 5.43 (d, J = 16.9 Hz, 1 H), 5.13 (d, J = 10.6 Hz, 1 H), 4.81 (s, 2 H), 3.30 (d, J = 5.8 Hz, 2 H), 2.30 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 142.6, 141.1, 137.0, 135.3, 135.2, 129.8, 129.6, 129.0, 128.8, 127.4, 127.3, 126.3, 125.0, 115.1, 53.5, 33.9, 21.4.

MS (EI): m/z = 325 (M⁺), 260, 170, 117, 91.

HRMS (EI): m/z calcd for C₁₉H₁₉NO₂S (M⁺): 325.1136; found: 325.1121.

Ethyl 2-[2-(p-Toluenesulfonyl)-2,5-dihydro-1H-benzo[c]azepin-3-yl]acrylate (53b)

According to the typical procedure for the metathesis reaction of 11a, a solution of 13b (35.7 mg, 0.09 mmol) and 1b (3.8 mg, 4.49 μmol) in toluene (4.5 mL) was stirred at 80 °C for 0.5 h under an argon atmosphere to afford 53b (29.9 mg, 84%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 3:1).

IR (neat): 1722 (s), 1599 (w), 1349 (s), 1162 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.28 (d, J = 7.7 Hz, 1 H), 7.11 (d, J = 7.7 Hz, 2 H), 7.20–7.09 (m, 2 H), 6.95 (d, J = 7.7 Hz, 2 H), 6.80 (d, J = 7.2 Hz, 1 H), 6.12 (d, J = 1.4 Hz, 1 H), 5.69 (d, J = 1.4 Hz, 1 H), 5.63 (t, J = 5.3 Hz, 1 H), 4.95 (s, 2H), 4.22 (q, J = 7.2 Hz, 2 H), 3.48 (d, J = 5.3 Hz, 2 H), 2.30 (s, 3 H), 1.33 (t, J = 7.2 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 165.7, 142.5, 141.4, 138.4, 136.5, 136.1, 135.9, 129.4, 129.2, 128.7, 127.6, 127.2, 126.5, 125.9, 124.4, 60.9, 54.4, 34.7, 21.4, 14.1.

MS (EI): m/z = 397 (M⁺), 352, 242, 196, 168, 117, 91.

HRMS (EI): m/z calcd for C₂₂H₂₃NO₄S (M⁺): 397.1348; found: 397.1364.

Dimethyl 5-(p-Toluenesulfonyl)-5,6,11,11a-tetrahydro-3H-dibenzo[b,e]azepine-1,2-dicarboxylate (54)

According to the typical procedure for the metathesis reaction of 11a, a solution of 13a (33.4 mg, 0.10 mmol) and 1b (4.4 mg, 5.13 μmol) in toluene (5.1 mL) was stirred at 80 °C for 0.5 h under an argon atmosphere. After cooling to r.t., DMAD (0.04 mL, 0.31 mmol) was added and the mixture was stirred at 80 °C for 29 h under an argon atmosphere. The volatiles were removed under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane/EtOAc 2:1) to provide 54 (17.1 mg, 36%) as a pale yellow oil.

IR (neat): 1732 (s), 1339 (m), 1160 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.38 (d, J = 8.2 Hz, 2 H), 7.32 (m, 1 H), 7.24–7.18 (m, 2 H), 7.09 (d, J = 8.2 Hz, 2 H), 7.00 (m, 1 H), 5.85 (dd, J = 3.4, 3.9 Hz, 1 H), 5.00 (d, J = 15.2 Hz, 1 H), 4.36 (d, J = 15.2 Hz, 1 H), 3.79 (s, 3 H), 3.77 (s, 3 H), 3.18–3.00 (m, 2 H), 2.92–2.83 (m, 2 H), 2.70 (dd, J = 9.2, 15.0 Hz, 1 H), 2.35 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 167.6, 167.4, 143.2, 139.0, 137.0, 136.6, 136.6, 136.2, 130.9, 129.5, 129.3, 129.3, 128.3, 127.3, 126.9, 124.4, 53.9, 52.4, 52.3, 39.7, 39.5, 28.4, 21.4.

MS (EI): m/z = 467 (M⁺), 436, 403, 371, 344, 280, 252, 213, 104.

HRMS (EI): m/z calcd for C₂₅H₂₅NO₆S (M⁺): 467.1403; found: 467.1378.

1-(p-Toluenesulfonyl)-7-vinyl-2,3,4,5-tetrahydro-1H-azepine (55a)

According to the typical procedure for the metathesis reaction of 11a, a solution of 17a (20.7 mg, 0.07 mmol) and 1b (6.3 mg, 7.46 μmol) in CH₂Cl₂ (4.0 mL) was stirred at reflux for 26 h under an argon atmosphere to afford 55a (7.7 mg, 37%) as a pale yellow oil together with 17a (6.8 mg, 33%).

IR (neat): 1599 (w), 1343 (s), 1158 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.76 (d, J = 8.2 Hz, 2 H), 7.27 (d, J = 8.2 Hz, 2 H), 6.25 (dd, J = 10.6, 17.2 Hz, 1 H), 5.94 (dd, J = 6.8, 7.3 Hz, 1 H), 5.29 (d, J = 17.2 Hz, 1 H), 5.05 (d, J = 10.6 Hz, 1 H), 3.49 (br, 2 H), 2.42 (s, 3 H), 1.90–1.84 (m, 2 H), 1.73–1.66 (m, 2 H), 1.36–1.29 (m, 2 H).

¹³C NMR (100 MHz, CDCl₃): δ = 143.1, 142.4, 139.1, 134.6, 131.9, 129.4, 127.5, 114.6, 49.1, 29.2, 26.0, 23.6, 21.5.

MS (EI): m/z = 277 (M⁺), 212, 155, 122, 91.

HRMS (EI): m/z calcd for C₁₅H₁₉NO₂S (M⁺): 277.1136; found: 277.1134.

Ethyl 2-[1-(p-Toluenesulfonyl)-4,5,6,7-tetrahydro-1H-azepin-2-yl]acrylinoate (55b)

According to the typical procedure for the metathesis reaction of 11a, a solution of 17b (21.2 mg, 0.06 mmol) and 1b (5.2 mg, 6.07 μmol) in CH₂Cl₂ (3.0 mL) was stirred at reflux for 1.5 h under an ethylene atmosphere to afford 55b (15.6 mg, 74%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/Et₂O 3:2).

IR (neat): 1715 (s), 1599 (w), 1344 (s), 1161 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.65 (d, J = 8.2 Hz, 2 H), 7.23 (d, J = 8.2 Hz, 2 H), 6.14 (d, J = 1.7 Hz, 1 H), 5.87 (t, J = 6.8 Hz, 1 H), 5.86 (d, J = 1.7 Hz, 1 H), 3.92 (q, J = 7.3 Hz, 2 H), 3.69–3.63 (m, 2 H), 2.40 (s, 3 H), 2.11–2.04 (m, 2 H), 1.88–1.81 (m, 2 H), 1.50–1.42 (m, 2 H), 1.16 (t, J = 7.3 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 165.7, 142.8, 139.8, 139.5, 138.4, 131.4, 129.3, 128.0, 127.2, 60.7, 50.7, 30.5, 27.0, 23.4, 21.5, 14.0.

MS (EI): m/z = 349 (M⁺), 304, 194, 166, 148, 120, 91.

HRMS (EI): m/z calcd for C₁₈H₂₃NO₄S (M⁺): 349.1348; found: 349.1339.

Ethyl 2-[1,5-Bis-(p-toluenesulfonyl)-4,5-dihydro-1H-benzo[b][1,4]diazepin-2-yl]acrylate (56b)

According to the typical procedure for the metathesis reaction of 11a, a solution of 21b (33.3 mg, 0.06 mmol) and 1b (5.1 mg, 6.03 μmol) in toluene (3.0 mL) was stirred at 80 °C for 0.5 h under an ethylene atmosphere to afford 56b (33.2 mg, 99%) as a white solid after the purification by column chromatography on silica gel (hexane/EtOAc 2:1); mp 187–188 °C.

IR (KBr): 1720 (m), 1598 (w), 1355 (s), 1164 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.87 (d, J = 8.2 Hz, 2 H), 7.72 (d, J = 8.2 Hz, 2 H), 7.46 (m, 1 H), 7.36–7.26 (m, 7 H), 6.25 (s, 1 H), 5.88 (s, 1 H), 5.30 (dd, J = 2.9, 3.9 Hz, 1 H), 4.57 (dd, J = 3.9, 18.4 Hz, 1 H), 4.15–4.06 (m, 2 H), 3.73 (dd, J = 2.9, 18.4 Hz, 1 H), 2.44 (s, 3 H), 2.42 (s, 3 H), 1.24 (t, J = 7.2 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 165.1, 144.0, 143.7, 140.3, 139.4, 137.8, 137.0, 136.9, 136.3, 130.4, 129.9, 129.5, 129.1, 128.4, 128.3, 128.1, 127.5, 125.7, 121.4, 61.0, 49.1, 21.6, 21.6, 14.1.

MS (EI): m/z = 552 (M⁺), 507, 397, 242, 169, 139, 91.

HRMS (EI): m/z calcd for C₂₈H₂₈N₂O₆S₂ (M⁺): 552.1389; found: 552.1399.

4-(1-Phenylvinyl)-1,5-bis-(p-toluenesulfonyl)-2,5-dihydro-1H-benzo[b][1,4]diazepine (56c)

According to the typical procedure for the metathesis reaction of 11a, a solution of 21c (41.9 mg, 0.08 mmol) and 1b (6.4 mg, 7.53 μmol) in toluene (3.8 mL) was stirred at 80 °C for 1 h under an ethylene atmosphere to afford 56c (40.7 mg, 97%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 2:1).

IR (neat): 1597 (m), 1356 (s), 1166 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.94 (d, J = 8.7 Hz, 2 H), 7.61–7.56 (m, 3 H), 7.38–7.32 (m, 3 H), 7.18 (d, J = 8.2 Hz, 2 H), 7.28–7.17 (m, 6 H), 7.10 (dd, J = 1.5, 7.7 Hz, 1 H), 5.39 (s, 1 H), 5.32 (dd, J = 3.4, 3.9 Hz, 1 H), 5.28 (s, 1 H), 4.54 (dd, J = 3.9, 18.4 Hz, 1 H), 3.79 (dd, J = 3.4, 18.4 Hz, 1 H), 2.44 (s, 3 H), 2.40 (s, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 147.8, 144.2, 143.6, 140.4, 139.2, 138.7, 138.7, 137.3, 136.1, 129.7, 129.6, 129.3, 129.2, 128.6, 128.3, 128.2, 128.0, 127.9, 127.2, 126.5, 122.0, 116.4, 48.8, 21.6, 21.5.

MS (EI): m/z = 556 (M⁺), 401, 301, 245, 145, 119, 91.

HRMS (EI): m/z calcd for C₃₁H₂₈N₂O₄S₂ (M⁺): 556.1490; found: 556.1481.

Ethyl 2-[1,5-Bis(toluene-4-sulfonyl)-1,4,5,6,7,8-hexahydro[1,5]diazocin-2-yl]acrylate (58b)

According to the typical procedure for the metathesis reaction of 11a, a solution of 46b (34.4 mg, 0.07 mmol) and 1b (5.6 mg, 6.63 μmol) in CH₂Cl₂ (33 mL) was stirred at reflux for 24 h under an argon atmosphere to afford 58b (26.8 mg, 78%) as a pale yellow oil after purification by column chromatography on silica gel (hexane/EtOAc 3:2).

IR (neat): 1717 (s), 1598 (w), 1343 (s), 1161 (s) cm^–1.

¹H NMR (400 MHz, CDCl₃): δ = 7.65 (d, J = 8.2 Hz, 2 H), 7.58 (d, J = 8.2 Hz, 2 H), 7.31 (d, J = 7.7 Hz, 2 H), 7.23 (d, J = 7.7 Hz, 2 H), 6.18 (t, J = 8.2 Hz, 1 H), 6.16 (s, 1 H), 5.81 (s, 1 H), 3.90 (q, J = 7.3 Hz, 2 H), 3.85 (d, J = 8.2 Hz, 2 H), 3.63 (t, J = 5.3 Hz, 2 H), 3.47–3.41 (m, 2 H), 2.44 (s, 3 H), 2.40 (s, 3 H), 1.93–1.86 (m, 2 H), 1.15 (t, J = 7.3 Hz, 3 H).

¹³C NMR (100 MHz, CDCl₃): δ = 165.0, 143.4, 143.4, 139.3, 137.8, 136.7, 136.2, 131.0, 130.5, 129.8, 129.4, 127.4, 127.0, 60.9, 51.8, 48.5, 44.1, 27.9, 21.5, 21.5, 13.9.

MS (EI): m/z = 518 (M⁺), 473, 397, 363, 335, 317, 267, 238, 207, 180, 155, 134, 91.

HRMS (EI): m/z calcd for C₂₅H₃₀N₂O₆S₂ (M⁺): 518.1545; found: 518.1538.

• References


For selected reports, see:
• 1a Zi G. Dalton Trans. 2009; 42: 9101
• 1b Muniz K. Hövelmann CH. Streuff J. Campos-Gomez E. Pure Appl. Chem. 2008; 80: 1089
• 1c Geurts K. Fletcher SP. van Zijl AW. Minnaard AJ. Feringa BL. Pure Appl. Chem. 2008; 80: 1025
• 1d Kalck P. Urrutigoity M. Dechy-Cabaret O. Top. Organomet. Chem. 2006; 18: 97
• 1e Netscher T. J. Organomet. Chem. 2006; 691: 5155
• 1f Wipf P. Kendall C. Top. Organomet. Chem. 2005; 8: 1
• 1g Grigg R. Sridharan V. Pure Appl. Chem. 1998; 70: 1047
• 1h Weber L. Angew. Chem., Int. Ed. Engl. 1996; 35: 271
• 2a Handbook of Metathesis . Vol. 1–3. Grubbs RH. Wiley-VCH; Weinheim: 2003
• 2b Topics in Organometallic Chemistry . Vol. 1. Fürstner A. Springer-Verlag; Berlin: 1998

For selected general reviews, see:
• 2c Montgomery TP. Ahmed TS. Grubbs RH. Angew. Chem. Int. Ed. 2017; 56: 11024
• 2d Higman CS. Lummiss JA. M. Fogg DE. Angew. Chem. Int. Ed. 2016; 55: 3552
• 2e Fustero S. Simon-Fuentes A. Barrio P. Haufe G. Chem. Rev. 2015; 115: 871
• 2f Herbert MB. Grubbs RH. Angew. Chem. Int. Ed. 2015; 54: 5018
• 2g Nelson DJ. Manzini S. Urbina-Blanco CA. Nolan SP. Chem. Commun. 2014; 50: 10355
• 2h Kress S. Blechert S. Chem. Soc. Rev. 2012; 41: 4389
• 2i Vougioukalakis GC. Grubbs RH. Chem. Rev. 2010; 110: 1746
• 2j Nolan SP. Clavier H. Chem. Soc. Rev. 2010; 39: 3305
• 2k Chauvin Y. Angew. Chem. Int. Ed. 2006; 45: 3740
• 2l Schrock RR. Angew. Chem. Int. Ed. 2006; 45: 3748
• 2m Grubbs RH. Angew. Chem. Int. Ed. 2006; 45: 3760
• 2n Hoveyda AH. Zhugralin AR. Nature 2007; 450: 243
• 2o Nicolaou KC. Bulger PG. Sarlah D. Angew. Chem. Int. Ed. 2005; 44: 4490
• 2p Fürstner A. Angew. Chem. Int. Ed. 2000; 39: 3012
• 2q Grubbs RH. Chang S. Tetrahedron 1998; 54: 4413
• 2r Schuster M. Blechert S. Angew. Chem. Int. Ed. 1997; 36: 2037
• 3a Mori M. Top. Organomet. Chem. 1998; 1: 133
• 3b Kotha S. Panguluri NR. Ali R. Eur. J. Org. Chem. 2017; 5316
• 3c Li J. Lee D. Eur. J. Org. Chem. 2011; 4269
• 3d Kotha S. Meshram M. Tiwari A. Chem. Soc. Rev. 2009; 38: 2065
• 3e Hansen EC. Lee D. Acc. Chem. Res. 2006; 39: 509
• 3f Diver ST. Giessert AJ. Chem. Rev. 2004; 104: 1317
• 3g Poulsen CS. Madsen R. Synthesis 2003; 1
• 3h Mori M. Sakakibara N. Kinoshita A. J. Org. Chem. 1998; 63: 6082
• 3i Kinoshita A. Mori M. J. Org. Chem. 1996; 61: 8356

For recent reviews on the chemistry of ynamines and ynamides, see:
• 4a Prabagar B. Ghosh N. Sahoo AK. Synlett 2017; 28: 2539
• 4b Duret G. Le Fouler V. Bisseret P. Bizet V. Blanchard N. Eur. J. Org. Chem. 2017; 6816
• 4c Hu L. Zhao J. Synlett 2017; 28: 1663
• 4d Cook AM. Wolf C. Tetrahedron Lett. 2015; 56: 2377
• 4e Wang X.-N. Yeom H.-S. Fang L.-C. He S. Ma Z.-X. Kedrowski BL. Hsung RP. Acc. Chem. Res. 2014; 47: 560
• 4f Evano G. Jouvin K. Coste A. Synthesis 2013; 45: 17
• 4g Evano G. Coste A. Jouvin K. Angew. Chem. Int. Ed. 2010; 49: 2840
• 4h DeKorver KA. Li H. Lohse AG. Hayashi R. Lu Z. Zhang Y. Hsung RP. Chem. Rev. 2010; 110: 5064
• 4i Brückner D. Tetrahedron 2006; 62: 3809
• 4j Zificsak CA. Mulder JA. Hsung RP. Rameshkumar C. Wei L.-L. Tetrahedron 2001; 57: 7575
• 5 Kitamura T. Kotani M. Fujiwara Y. Synthesis 1998; 1416
• 6 Brückner D. Synlett 2000; 1402
• 7 Zhang Y. Hsung RP. Tracey MR. Kurtz KC. M. Vera EL. Org. Lett. 2004; 6: 1151

For recent examples of transition-metal-catalyzed reaction of ynamides, see:
• 8a Gao Y. Wu G. Zhou Q. Wang J. Angew. Chem. Int. Ed. 2018; 57: 2716
• 8b Liu X. Zhang Z.-X. Zhou B. Wang Z.-S. Zheng R.-H. Ye L.-W. Org. Biomol. Chem. 2017; 15: 10156
• 8c Song W. Zheng N. Org. Lett. 2017; 19: 6200
• 8d Alexander JR. Cook MJ. Org. Lett. 2017; 19: 5822
• 8e Han X.-L. Zhou C.-J. Liu X.-G. Zhang S.-S. Wang H. Li Q. Org. Lett. 2017; 19: 6108
• 8f Giri SS. Liu R.-S. Adv. Synth. Catal. 2017; 359: 3311
• 8g Witulski B. Stengel T. Angew. Chem. Int. Ed. 1998; 37: 489
• 8h Witulski B. Gößmann M. Chem. Commun. 1999; 1879
• 8i Couty S. Meyer C. Cossy J. Angew. Chem. Int. Ed. 2006; 45: 6726
• 8j Zhang X. Hsung RP. Li H. Chem. Commun. 2007; 2420
• 8k Dunetz JR. Danheiser RL. J. Am. Chem. Soc. 2005; 127: 5776
• 8l Riddell N. Villeneuve K. Tam W. Org. Lett. 2005; 7: 3681
• 8m Tracey MR. Zhang Y. Frederick MO. Mulder JA. Hsung RP. Org. Lett. 2004; 6: 2209
• 8n Wakamatsu H. Takeshita M. Synlett 2010; 2322
• 9a Mori M. Wakamatsu H. Saito N. Sato Y. Narita R. Sato Y. Fujita R. Tetrahedron 2006; 62: 3872
• 9b Saito N. Sato Y. Mori M. Org. Lett. 2002; 4: 803
• 10 Wakamatsu H. Sakagami M. Hanata M. Takeshita M. Mori M. Macromol. Symp. 2010; 293: 5
• 11 Correa A. Tellitu I. Domínguez E. SanMartin R. J. Org. Chem. 2006; 71: 8316
• 12a Sherman ES. Fuller PH. Kasi D. Chemler SR. J. Org. Chem. 2007; 72: 3896
• 12b Fustero S. Moscardó J. Jiménez D. Pérez-Carrión MD. Sánchez-Roselló M. del Pozo C. Chem. Eur. J. 2008; 14: 9868
• 13 Bennasar ML. Roca T. Monerris M. García-Díaz D. J. Org. Chem. 2006; 71: 7028
• 14a Eymery F. Iorga B. Savignac P. Synthesis 2000; 185
• 14b Corey EJ. Fuchs PL. Tetrahedron Lett. 1972; 3769
• 15a Baba S. Negishi E. J. Am. Chem. Soc. 1976; 98: 6729
• 15b Rodríguez D. Castedo L. Saá C. Synlett 2004; 783
• 16a Mitsunobu O. Synthesis 1981; 1
• 16b Hughes DL. Org. React. 1992; 42: 335
• 17 Stetter H. Chem. Ber. 1953; 86: 161
• 18a Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett. 1975; 4467
• 18b Chinchilla R. Nájera C. Chem. Rev. 2007; 107: 874
• 19 Nicolaou KC. Jung J. Yoon WH. Fong KC. Choi H.-S. He Y. Zhong Y.-L. Baran PS. J. Am. Chem. Soc. 2002; 124: 2183
• 20a Lovely CJ. Mahmud H. Tetrahedron Lett. 1999; 40: 2079
• 20b Mahmud H. Lovely CJ. Rasika Dias HV. Tetrahedron 2001; 57: 4095
• 21 Similar result was also obtained in the previous study, see ref. 9.
• 22 Sohn J.-H. Kim KH. Lee H.-Y. No ZS. Ihee H. J. Am. Chem. Soc. 2008; 130: 16506