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DOI: 10.1055/s-0037-1609857
Synthesis of Various Heterocycles Having a Dienamide Moiety by Ring-Closing Metathesis of Ene-ynamides
Publication History
Received: 23 March 2018
Accepted after revision: 23 April 2018
Publication Date:
30 May 2018 (online)
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.
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Key words
ruthenium carbene complex - ynamide - ring-closing metathesis - heterocycles - medium-sized ringCarbon–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]
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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]
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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]).
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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]).
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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]).
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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).
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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]).
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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).
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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.
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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.
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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).
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).
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]).
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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).
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.
a Isolated yield.
b Reactions were carried out in the presence of 5 mol% 1b in toluene at 80 °C.
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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).
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
#
#
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1609857.
- Supporting Information
-
References
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- 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
- 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
- 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
- 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
- 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
For selected reports, see:
For selected general reviews, see:
For recent reviews on the chemistry of ynamines and ynamides, see:
For recent examples of transition-metal-catalyzed reaction of ynamides, see:
-
References
- 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
- 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
- 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
- 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
- 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
For selected reports, see:
For selected general reviews, see:
For recent reviews on the chemistry of ynamines and ynamides, see:
For recent examples of transition-metal-catalyzed reaction of ynamides, see:
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