Highly selective intramolecular addition of C–N and S–N bonds to alkynes catalyzed by palladium: a practical access to two distinct functional indoles

Abstract

Palladium-catalyzed highly selective intramolecular addition of C–N and S–N bonds to alkynes has been achieved, and two distinct functional indoles were synthesized rapidly from the same set of substrates in a catalyst-controlled manner. This protocol features high atom economy, moderate to high yields and excellent selectivity, thus affording a practical approach to functional indoles.

---

Introduction

Diversity-oriented synthesis (DOS) represents rapid and convenient access to molecular complexity and diversity.¹ It has received wide attention because of its high efficiency in constructing structurally complex and diverse molecules,² which can improve the hit rates of drug screening.³ In particular, the intramolecular cyclization transformations of DOS substrates have become an important strategy to generate highly functionalized heterocyclic compounds.⁴ However, most of the reported cyclization processes are defined single chemical reactions, thus generally leading to single heterocyclic products. This is in part attributed to the challenge of achieving high levels of chemoselectivity.⁵ Therefore, the power of DOS would be reinforced if the same materials could be diverged to different heterocyclic products. It is fascinating but also challenging to synthesize distinct sets of heterocyclic compounds from the same set of substrates in a highly selective manner, providing greater flexibility and efficiency.⁶ In our ongoing efforts to develop novel convenient and efficient approaches to synthesize valuable heterocyclic compounds, we herein report the rapid and highly selective synthesis of two distinct functional indoles from the same set of substrates in a catalyst-controlled manner.

Transition metal-catalyzed addition of X–Y (X, Y = H, B, C, N, O, Si, S, Cl, Se, etc.) bonds to alkynes forms an important strategy for the functionalization of carbon–carbon triple bonds.^7–12 Particularly, the intramolecular addition of X–Y bonds to alkynes has become an efficient strategy to synthesize functional cyclic compounds such as indoles,⁸ indenes,⁹ indenones,¹⁰ benzofurans,¹¹ benzothiophenes,¹² benzosiloles,¹³ oxindoles,¹⁴ isoxazoles,¹⁵ furans,¹⁶ pyrroles,¹⁷ pyrrolidinones,^14a,b azetidin-2-ones,¹⁸ piperidin-2-ones,^14b,c,18 azepan-2-ones^14b,18 and 1,2-oxaborolanes.¹⁹ Despite the remarkable achievements made, however, among the most reported methods, one specific metal only catalyzed the intramolecular addition of one specific kind of X–Y bond to alkynes with the migration of one specific kind of functional group. Based on our previous research,^8c,d in the present work, we realized the highly selective intramolecular addition of C–N and S–N bonds to alkynes using the same metal palladium with different oxidation states, and the allyl group and sulfonyl group²⁰ can display as migrating groups when employing Pd(0) and Pd(II) catalysts, respectively (Scheme 1). In our catalytic system, two distinct kinds of functional indoles were synthesized rapidly and selectively from the same set of substrates in a catalyst-controlled manner. To the best of our knowledge, this is the first report of selective intramolecular addition of different X–Y bonds to alkynes catalyzed by the same metal to furnish distinct heterocyclic compounds from the same substrates.

Scheme 1 Selective intramolecular addition of C–N and S–N bonds to alkynes catalyzed by palladium.

Results and discussion

Screening experiments were performed employing 1a as the model substrate to optimize the intramolecular addition conditions for catalysts and solvents (Table 1). Initially, substrate 1a was subjected to Pd(0) catalysts such as Pd₂(dba)₃ and Pd(PPh₃)₄ in toluene at 90 °C for 8 h (entries 1 and 2). To our delight, the C–N addition product 2a was achieved when Pd(PPh₃)₄ was used as the catalyst, albeit with low yield (entry 2). An examination of the solvents revealed that the transformation was significantly influenced by the solvent used. Moderate yields (56–78%) were obtained in THF, DCE, DMF and DMSO (entries 3, 4, 8 and 9), a high yield (83%) was achieved in 1,4-dioxane (entry 5), and no desired product was detected in EtOH (entry 7). Pleasingly, 2a was exclusively afforded in CH₃CN with almost quantitative yield (entry 6). Subsequently, optimization of the reaction conditions of Pd(II) catalyzed intramolecular addition of S–N bond to alkynes was carried out. Treatment of 1a with Pd(II) catalysts such as Pd(OAc)₂ in CH₃CN at 90 °C for 8 h provided the S–N addition product 3a in 16% yield (entry 10). Encouraged by this result, an investigation of other Pd(II) sources was conducted (entries 11–16). Among them, PdCl₂(CH₃CN)₂ displayed the highest catalytic reactivity, providing product 3a with 92% yield (entry 16). In addition, screening of solvents revealed that CH₃CN was the most suitable solvent for this reaction (entries 16–20). In this way, two distinct functional indoles were generated rapidly from the same set of substrates in a catalyst-controlled manner with high selectivity.

Table 1 Survey of the reaction conditions for the divergent transformations of 1a

Entry	Catalyst	Solvent	Yield^a (%)
			2a^b	3a^c
a Isolated yield.b 1a (0.4 mmol), Pd(0) (0.04 mmol), and solvent (2.0 ml) under an argon atmosphere at 90 °C for 8 h.c 1a (0.4 mmol), Pd(II) (0.04 mmol), and solvent (2.0 ml) under an argon atmosphere at 90 °C for 8 h. “—” means that product was not detected.
1	Pd2(dba)3	Toluene	Trace	—
2	Pd(PPh3)4	Toluene	5	—
3	Pd(PPh3)4	THF	56	—
4	Pd(PPh3)4	DCE	62	—
5	Pd(PPh3)4	1,4-Dioxane	83	—
6	Pd(PPh3)4	CH3CN	99	—
7	Pd(PPh3)4	EtOH	0	—
8	Pd(PPh3)4	DMF	78	—
9	Pd(PPh3)4	DMSO	56	—
10	Pd(OAc)2	CH3CN	—	16
11	PdCl2	CH3CN	—	47
12	PdCl2(dppf)2	CH3CN	—	0
13	(NH4)2PdCl4	CH3CN	—	11
14	Na2PdCl4	CH3CN	—	59
15	PdCl2(PhCN)2	CH3CN	—	84
16	PdCl2(CH3CN)2	CH3CN	—	92
17	PdCl2(CH3CN)2	Toluene	—	81
18	PdCl2(CH3CN)2	DCE	—	77
19	PdCl2(CH3CN)2	EtOH	—	0
20	PdCl2(CH3CN)2	DMSO	—	6

---

These selective conditions were then applied to synthesize a wide range of 3-allyl-1-sulfonyl-indoles (2) and 1-allyl-3-sulfonyl-indoles (3) from the same set of substrates (1). The results are summarized in Table 2. In general, the protocol was compatible with aliphatic and aromatic substituents at R₁ and R₂, as well as halogens, electron-donating and electron-withdrawing groups at R₃, and all the indole products were obtained with high yields in a highly selective manner. In the case of Pd(PPh₃)₄ catalyzed intramolecular addition of C–N bond to alkynes, the protocol showed high yields (85–99%) for substrates with aliphatic and aromatic substituents at R₁ (2a–2d). Pleasingly, the reactions of 1e–1f carrying functional groups such as ester and halogen at R₁ afforded the corresponding products 2e–2f in excellent yields (90–92%). High yields (88–93%) were also achieved from 1g–1i with aliphatic and aromatic substituents at R₂ (2g–2i). In addition, substrates bearing halogens (F, Cl, Br), electron-donating group (Me) and electron-withdrawing substituents (CN, CF₃) at R₃ furnished the corresponding products 2j–2o in high yields (86–92%). Similarly, for the PdCl₂(CH₃CN)₂ catalyzed intramolecular addition of S–N bond to alkynes, the approach was compatible with aliphatic and aromatic substituents at R₁ and R₂ with moderate to high yields (3a–3i). The reactions of substrates having halogens (F, Cl, Br), electron-donating group (Me) and electron-withdrawing substituents (CN, CF₃) at R₃ also achieved the desired products 3j–3o in 77–87% yields.

Table 2 Divergent synthesis of two distinct indole compounds 2 and 3

Entry	Yield^a (%)
	2^b	3^c
a Isolated yield.b 1 (0.4 mmol), Pd(PPh3)4 (0.04 mmol), and CH3CN (2.0 mL) under an argon atmosphere at 90 °C for 8 h.c 1 (0.4 mmol), PdCl2(CH3CN)2 (0.04 mmol), and CH3CN (2.0 mL) under an argon atmosphere at 90 °C for 8 h.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15

---

Thus, from the same set of substrates, two distinct functional indoles were prepared easily by simply switching the palladium catalyst. Our protocol exhibits valuable features of high selectivity, moderate to high yields and high atom economy. Such a divergent synthesis of functional indoles is evidently useful in diversity-oriented synthesis.

The chemical structures of compounds 2 and 3 were characterized and differentiated by comparing their ¹H NMR spectra. The allyl hydrogens of compounds 2 generally display much lower chemical shifts than the allyl hydrogens of compounds 3. For example, the chemical shift of the allyl hydrogens (H_a) of compounds 2a is 3.44 ppm, while the chemical shift of the allyl hydrogens (H_b) of compounds 3a is 4.77 ppm (Fig. 1).

Fig. 1 Structural characterization of compounds 2a and 3a.

The proposed catalytic cycle of Pd(0)-catalyzed intramolecular addition of C–N bond to alkynes was outlined in Scheme 2. Oxidative addition of the allyl amine group to the Pd(0) catalyst forms intermediate A1, then palladium-promoted ionization of the C–N bond offers intermediate B1, followed by nucleophilic attack of the nitrogen to the activated carbon–carbon triple bond, producing intermediate C1. Reductive elimination of the Pd(0) catalyst then gives the products.

Scheme 2 Proposed reaction mechanism of Pd(0)-catalyzed intramolecular addition of C–N bond to alkynes.

A plausible mechanism of Pd(II)-catalyzed intramolecular addition of S–N bond to alkynes was also proposed as shown in Scheme 3. Coordination of alkyne to the Pd(II) catalyst yields intermediate A2, followed by nucleophilic attack of nitrogen to the alkyne, affording intermediate B2. An intramolecular [1,3]-migration of the sulfonyl group then gives intermediate C2, which affords the products and regenerates the catalyst.

Scheme 3 Proposed reaction mechanism Pd(II)-catalyzed intramolecular addition of S–N bond to alkynes.

Conclusions

We have developed a practical and efficient approach to synthesize two distinct functional indoles through the highly selective intramolecular addition of C–N and S–N bonds to alkynes catalyzed by palladium. The catalyst-controlled synthetic strategy features high atom economy, moderate to high yields and excellent selectivity. We anticipate that these functional indoles may find pharmaceutical applications after further investigations.

Experimental section

General information

The reagents were purchased from commercial suppliers and used without further purification. Analytical thin-layer chromatography (TLC) was performed on HSGF 254 (0.15–0.2 mm thickness), visualized by irradiation with UV light (254 nm). Column chromatography was performed using silica gel FCP 200-300. Melting points were measured with a micro melting point apparatus. Nuclear magnetic resonance spectra were recorded on a Brucker AMX-400 MHz instrument (TMS as IS). Chemical shifts were reported in parts per million (ppm, δ) downfield from tetramethylsilane. Proton coupling patterns were described as singlet (s), doublet (d), triplet (t), quartet (q), multiplet (m), and broad (br). Low and high-resolution mass were measured by the EI method with a Tsou-EI mass spectrometer.

General procedure for the preparation of 2

A long reaction tube (about fifteen centimeter length) equipped with a magnetic stir bar was charged with 1 (0.4 mmol), Pd(PPh₃)₄ (0.04 mmol), and CH₃CN (2.0 ml) and capped with septa. Then the reaction tube was evacuated and backfilled with argon, and the process was repeated three times. After that, the reaction tube was kept in the pre-heated oil bath at 90 °C and stirred under reflux for 8 h. After removal of the solvent, the residue was purified by flash chromatography on silica gel (PE : EA = 16 : 1) to give the desired product 2.

General procedure for the preparation of 3

A long reaction tube (about fifteen centimeter length) equipped with a magnetic stir bar was charged with 1 (0.4 mmol), PdCl₂(CH₃CN)₂ (0.04 mmol), and CH₃CN (2.0 mL) and capped with septa. Then the reaction tube was evacuated and backfilled with argon, and the process was repeated three times. After that, the reaction tube was kept in the pre-heated oil bath at 90 °C and stirred under reflux for 8 h. After removal of the solvent, the residue was purified by flash chromatography on silica gel (PE : EA = 8 : 1) to give the desired product 3.

Characterization data

3-Allyl-2-butyl-1-(methylsulfonyl)-1H-indole (2a). White solid (115.4 mg, yield 99%), mp 42–43 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.07–7.99 (m, 1H), 7.52–7.46 (m, 1H), 7.33–7.26 (m, 2H), 6.00–5.88 (m, 1H), 5.12–5.03 (m, 2H), 3.44 (d, J = 6.0 Hz, 2H), 3.00–2.90 (m, 5H), 1.70–1.61 (m, 2H), 1.46–1.36 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 138.56, 136.48, 135.73, 130.84, 124.35, 123.70, 119.13, 118.27, 115.90, 114.65, 39.96, 32.95, 28.71, 26.01, 22.85, 13.97; EI-MS (m/z): 291 (M⁺); HRMS (EI) calcd for C₁₆H₂₁NO₂S (M⁺) 291.1293, found: 291.1296.

1-Allyl-2-butyl-3-(methylsulfonyl)-1H-indole (3a). Yellow solid (107.2 mg, yield 92%), mp 65–66 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.06–7.95 (m, 1H), 7.34–7.24 (m, 3H), 6.02–5.89 (m, 1H), 5.22 (d, J = 10.6 Hz, 1H), 4.91 (d, J = 17.0 Hz, 1H), 4.77 (d, J = 3.8 Hz, 2H), 3.17–3.08 (m, 5H), 1.71–1.60 (m, 2H), 1.54–1.45 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 146.26, 135.86, 132.00, 125.19, 123.19, 122.47, 119.71, 117.64, 110.39, 45.97, 45.81, 32.54, 24.47, 22.97, 13.89; EI-MS (m/z): 291 (M⁺); HRMS (EI) calcd for C₁₆H₂₁NO₂S (M⁺) 291.1293, found: 291.1292.

3-Allyl-2-cyclopropyl-1-(methylsulfonyl)-1H-indole (2b). Pale yellow solid (100.2 mg, yield 91%), mp 84–85 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.99 (d, J = 8.0 Hz, 1H), 7.49–7.43 (m, 1H), 7.32–7.24 (m, 2H), 6.04–5.92 (m, 1H), 5.06 (dd, J = 10.1, 1.6 Hz, 1H), 4.97 (dd, J = 17.1, 1.7 Hz, 1H), 3.56 (d, J = 5.6 Hz, 2H), 3.08 (s, 3H), 2.10–2.01 (m, 1H), 1.11–1.05 (m, 2H), 0.83–0.77 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 138.33, 136.28, 135.79, 130.54, 124.68, 123.43, 119.41, 119.12, 115.91, 114.30, 40.62, 28.87, 8.51, 7.58; EI-MS (m/z): 275 (M⁺); HRMS (EI) calcd for C₁₅H₁₇NO₂S (M⁺) 275.0980, found: 275.0978.

1-Allyl-2-cyclopropyl-3-(methylsulfonyl)-1H-indole (3b). Brown oil (96.9 mg, yield 88%). ¹H NMR (400 MHz, CDCl₃) δ 8.12–8.03 (m, 1H), 7.34–7.22 (m, 3H), 6.05–5.91 (m, 1H), 5.27–5.18 (m, 1H), 5.02–4.97 (m, 2H), 4.94–4.88 (m, 1H), 3.19 (s, 3H), 2.03–1.95 (m, 1H), 1.30–1.21 (m, 2H), 1.07–1.00 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 144.59, 135.38, 132.24, 125.15, 123.40, 122.44, 120.08, 117.29, 113.09, 110.45, 46.41, 45.69, 7.74, 6.69; EI-MS (m/z): 275 (M⁺); HRMS (EI) calcd for C₁₅H₁₇NO₂S (M⁺) 275.0980, found: 275.0984.

3-Allyl-2-cyclohexyl-1-(methylsulfonyl)-1H-indole (2c). Pale yellow solid (120.6 mg, yield 95%), mp 72–73 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.09–8.04 (m, 1H), 7.49–7.44 (m, 1H), 7.29–7.25 (m, 2H), 6.07–5.92 (m, 1H), 5.16–5.01 (m, 2H), 3.69–3.55 (m, 3H), 2.97 (s, 3H), 1.94–1.77 (m, 6H), 1.50–1.27 (m, 4H); ¹³C NMR (101 MHz, CDCl₃) δ 142.13, 136.38, 135.84, 131.46, 124.33, 123.53, 118.91, 118.39, 116.11, 115.13, 40.38, 36.92, 32.39, 29.40, 27.16, 26.03; EI-MS (m/z): 317 (M⁺); HRMS (EI) calcd for C₁₈H₂₃NO₂S (M⁺) 317.1449, found: 317.1444.

1-Allyl-2-cyclohexyl-3-(methylsulfonyl)-1H-indole (3c). Brown solid (45.7 mg, yield 36%), mp 62–63 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.71 (d, J = 7.6 Hz, 1H), 7.49 (d, J = 8.2 Hz, 1H), 7.25–7.20 (m, 1H), 6.73 (s, 1H), 6.02–5.88 (m, 1H), 5.16 (d, J = 10.5 Hz, 1H), 4.86–4.75 (m, 3H), 3.13 (s, 3H), 2.70–2.61 (m, 1H), 2.04–1.98 (m, 2H), 1.91–1.86 (m, 2H), 1.83–1.75 (m, 2H), 1.60–1.51 (m, 2H), 1.45–1.36 (m, 2H); ¹³C NMR (126 MHz, CDCl₃) δ 150.29, 137.73, 133.06, 129.63, 125.19, 120.68, 119.93, 116.92, 115.15, 96.72, 45.64, 43.89, 36.22, 33.60, 26.70, 26.13; EI-MS (m/z): 317 (M⁺); HRMS (EI) calcd for C₁₈H₂₃NO₂S (M⁺) 317.1449, found: 317.1452.

3-Allyl-1-(methylsulfonyl)-2-phenyl-1H-indole (2d). White solid (105.9 mg, yield 85%), mp 128–130 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.16 (dd, J = 7.2, 1.3 Hz, 1H), 7.63–7.60 (m, 1H), 7.49–7.35 (m, 7H), 6.03–5.91 (m, 1H), 5.11–5.01 (m, 2H), 3.36–3.31 (m, 2H), 2.79 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 137.31, 137.10, 135.90, 131.09, 130.91, 130.75, 128.92, 127.86, 125.29, 124.21, 121.13, 119.93, 115.98, 115.56, 39.85, 28.88; EI-MS (m/z): 311 (M⁺); HRMS (EI) calcd for C₁₈H₁₇NO₂S (M⁺) 311.0980, found: 311.0978.

1-Allyl-3-(methylsulfonyl)-2-phenyl-1H-indole (3d). Pale yellow solid (98.4 mg, yield 79%), mp 122–123 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.22–8.18 (m, 1H), 7.54–7.45 (m, 5H), 7.41–7.34 (m, 3H), 5.90–5.79 (m, 1H), 5.19 (dd, J = 10.4, 0.8 Hz, 1H), 4.90 (dd, J = 17.1, 0.8 Hz, 1H), 4.57–4.54 (m, 2H), 2.95 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 144.05, 135.57, 132.26, 130.72, 130.13, 128.92, 128.36, 125.12, 123.89, 122.83, 120.61, 117.73, 113.03, 110.97, 46.71, 45.83; EI-MS (m/z): 311 (M⁺); HRMS (EI) calcd for C₁₈H₁₇NO₂S (M⁺) 311.0980, found: 311.0986.

3-(3-Allyl-1-(methylsulfonyl)-1H-indol-2-yl)propyl acetate (2e). Colourless oil (123.4 mg, yield 92%). ¹H NMR (400 MHz, CDCl₃) δ 8.03–7.98 (m, 1H), 7.52–7.47 (m, 1H), 7.32–7.25 (m, 2H), 5.99–5.86 (m, 1H), 5.11–5.01 (m, 2H), 4.10 (t, J = 6.3 Hz, 2H), 3.46–3.42 (m, 2H), 3.06–3.00 (m, 2H), 2.93 (s, 3H), 2.06–1.99 (m, 5H); ¹³C NMR (101 MHz, CDCl₃) δ 171.12, 136.71, 136.44, 135.39, 130.55, 124.59, 123.75, 119.22, 119.01, 115.97, 114.52, 63.75, 39.83, 29.37, 28.49, 22.78, 21.00; EI-MS (m/z): 335 (M⁺); HRMS (EI) calcd for C₁₇H₂₁NO₄S (M⁺) 335.1191, found: 335.1196.

3-(1-Allyl-3-(methylsulfonyl)-1H-indol-2-yl)propyl acetate (3e). Yellow oil (116.7 mg, yield 87%). ¹H NMR (400 MHz, CDCl₃) δ 7.97 (dd, J = 6.9, 2.2 Hz, 1H), 7.34–7.25 (m, 3H), 6.01–5.88 (m, 1H), 5.23 (d, J = 10.4 Hz, 1H), 4.92 (d, J = 17.1 Hz, 1H), 4.82–4.74 (m, 2H), 4.18 (t, J = 6.2 Hz, 2H), 3.23–3.17 (m, 2H), 3.12 (s, 3H), 2.07–1.99 (m, 5H); ¹³C NMR (101 MHz, CDCl₃) δ 171.13, 144.65, 135.84, 131.82, 124.96, 123.42, 122.58, 119.61, 117.73, 110.74, 110.43, 63.71, 45.83, 45.73, 29.31, 21.39, 21.01; EI-MS (m/z): 335 (M⁺); HRMS (EI) calcd for C₁₇H₂₁NO₄S (M⁺) 335.1191, found: 335.1188.

3-Allyl-2-(3-chloropropyl)-1-(methylsulfonyl)-1H-indole (2f). White solid (112.3 mg, yield 90%), mp 52–53 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.06–8.00 (m, 1H), 7.55–7.51 (m, 1H), 7.35–7.27 (m, 2H), 6.02–5.91 (m, 1H), 5.14–5.06 (m, 2H), 3.59 (t, J = 6.2 Hz, 2H), 3.50 (d, J = 6.0 Hz, 2H), 3.16–3.09 (m, 2H), 2.94 (s, 3H), 2.24–2.13 (m, 2H); ¹³C NMR (101 MHz, CDCl₃) δ 136.57, 136.33, 135.50, 130.65, 124.75, 123.90, 119.59, 119.37, 116.06, 114.65, 44.69, 39.85, 33.14, 28.57, 23.59; EI-MS (m/z): 313 (M⁺, (Cl³⁷)), 311 (M⁺, (Cl³⁵)); HRMS (EI) calcd for C₁₅H₁₈ClNO₂S (M⁺) 311.0747, found: 311.0744.

1-Allyl-2-(3-chloropropyl)-3-(methylsulfonyl)-1H-indole (3f). Pale yellow solid (109.8 mg, yield 88%), mp 60–62 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.05–7.94 (m, 1H), 7.40–7.23 (m, 3H), 6.09–5.90 (m, 1H), 5.26 (d, J = 10.4 Hz, 1H), 4.96 (d, J = 17.1 Hz, 1H), 4.90–4.78 (m, 2H), 3.70 (t, J = 6.0 Hz, 2H), 3.36–3.25 (m, 2H), 3.15 (s, 3H), 2.24–2.11 (m, 2H); ¹³C NMR (126 MHz, CDCl₃) δ 144.35, 135.87, 131.86, 124.96, 123.50, 122.64, 119.62, 117.83, 110.93, 110.50, 45.89, 45.77, 44.76, 33.18, 22.40; EI-MS (m/z): 313 (M⁺, (Cl³⁷)), 311 (M⁺, (Cl³⁵)); HRMS (EI) calcd for C₁₅H₁₈ClNO₂S (M⁺) 311.0747, found: 311.0746.

3-Allyl-2-butyl-1-(ethylsulfonyl)-1H-indole (2g). Colourless oil (113.6 mg, yield 93%). ¹H NMR (400 MHz, CDCl₃) δ 8.04–7.98 (m, 1H), 7.51–7.45 (m, 1H), 7.29–7.24 (m, 2H), 6.02–5.88 (m, 1H), 5.12–5.01 (m, 2H), 3.44 (d, J = 5.9 Hz, 2H), 3.17 (q, J = 7.4 Hz, 2H), 2.95–2.91 (m, 2H), 1.72–1.63 (m, 2H), 1.44–1.37 (m, 2H), 1.16 (t, J = 7.4 Hz, 3H), 0.94 (t, J = 7.4 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 139.21, 136.59, 135.79, 130.53, 124.12, 123.43, 119.06, 117.37, 115.76, 114.56, 48.20, 33.17, 28.60, 26.12, 22.85, 13.96, 7.84; EI-MS (m/z): 305 (M⁺); HRMS (EI) calcd for C₁₇H₂₃NO₂S (M⁺) 305.1449, found: 305.1448.

1-Allyl-2-butyl-3-(ethylsulfonyl)-1H-indole (3g). Brown oil (112.4 mg, yield 92%). ¹H NMR (400 MHz, CDCl₃) δ 8.02–7.92 (m, 1H), 7.32–7.21 (m, 3H), 6.01–5.87 (m, 1H), 5.20 (d, J = 10.4 Hz, 1H), 4.86 (d, J = 17.1 Hz, 1H), 4.79–4.74 (m, 2H), 3.18 (q, J = 7.4 Hz, 2H), 3.12–3.03 (m, 2H), 1.69–1.56 (m, 2H), 1.52–1.45 (m, 2H), 1.27 (t, J = 7.4 Hz, 3H), 0.96 (t, J = 7.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 147.11, 135.88, 131.99, 125.55, 123.08, 122.34, 119.87, 117.39, 110.33, 107.91, 51.71, 45.74, 32.73, 24.59, 22.98, 13.87, 7.82; EI-MS (m/z): 305 (M⁺); HRMS (EI) calcd for C₁₇H₂₃NO₂S (M⁺) 305.1449, found: 305.1452.

3-Allyl-2-butyl-1-(phenylsulfonyl)-1H-indole (2h). Colourless oil (124.4 mg, yield 88%). ¹H NMR (400 MHz, CDCl₃) δ 8.15 (d, J = 8.2 Hz, 1H), 7.62 (dd, J = 8.3, 1.0 Hz, 2H), 7.45–7.38 (m, 1H), 7.35–7.26 (m, 3H), 7.23–7.14 (m, 2H), 5.89–5.76 (m, 1H), 4.93 (dd, J = 10.1, 1.4 Hz, 1H), 4.82 (dd, J = 17.1, 1.6 Hz, 1H), 3.36–3.27 (m, 2H), 2.92 (t, J = 7.8 Hz, 2H), 1.68–1.59 (m, 2H), 1.41–1.33 (m, 2H), 0.90 (t, J = 7.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 138.96, 138.65, 136.94, 135.57, 133.50, 130.94, 129.12, 126.22, 124.18, 123.62, 118.89, 118.79, 115.63, 115.40, 33.04, 28.50, 26.37, 22.86, 13.96; EI-MS (m/z): 353 (M⁺); HRMS (EI) calcd for C₂₁H₂₃NO₂S (M⁺) 353.1449, found: 353.1445.

1-Allyl-2-butyl-3-(phenylsulfonyl)-1H-indole (3h). Brown solid (124.4 mg, yield 88%), mp 63–64 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.04–7.86 (m, 3H), 7.61–7.52 (m, 2H), 7.52–7.35 (m, 3H), 6.34 (d, J = 0.8 Hz, 1H), 5.99–5.86 (m, 1H), 5.14 (dd, J = 10.3, 0.9 Hz, 1H), 4.83–4.73 (m, 3H), 2.71 (t, J = 7.8 Hz, 2H), 1.75–1.67 (m, 2H), 1.48–1.40 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 146.27, 143.17, 135.78, 132.76, 132.63, 132.57, 131.83, 129.15, 127.38, 120.45, 118.69, 116.83, 109.87, 100.09, 45.58, 30.45, 26.52, 22.60, 13.99; EI-MS (m/z): 353 (M⁺); HRMS (EI) calcd for C₂₁H₂₃NO₂S (M⁺) 353.1449, found: 353.1447.

3-Allyl-2-butyl-1-tosyl-1H-indole (2i). Colourless oil (130.8 mg, yield 89%). ¹H NMR (400 MHz, CDCl₃) δ 8.28–8.15 (m, 1H), 7.59 (dd, J = 8.4, 1.6 Hz, 2H), 7.43–7.37 (m, 1H), 7.30–7.20 (m, 2H), 7.14 (d, J = 8.5 Hz, 2H), 5.97–5.84 (m, 1H), 5.09–4.84 (m, 2H), 3.48–3.33 (m, 2H), 3.05–2.96 (m, 2H), 2.31 (s, 3H), 1.75–1.67 (m, 2H), 1.49–1.40 (m, 2H), 0.97 (t, J = 7.3 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 144.47, 138.63, 136.87, 136.05, 135.62, 130.89, 129.69, 126.23, 124.05, 123.47, 118.81, 118.55, 115.57, 115.35, 33.06, 28.50, 26.36, 22.85, 21.54, 13.95; EI-MS (m/z): 367 (M⁺); HRMS (EI) calcd for C₂₂H₂₅NO₂S (M⁺) 367.1606, found: 367.1608.

1-Allyl-2-butyl-3-tosyl-1H-indole (3i). Brown solid (95.6 mg, yield 65%), mp 105–106 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.15–8.09 (m, 1H), 7.86 (d, J = 8.2 Hz, 2H), 7.26–7.19 (m, 5H), 6.02–5.81 (m, 1H), 5.18 (d, J = 10.4 Hz, 1H), 4.86 (d, J = 17.2 Hz, 1H), 4.72 (d, J = 4.5 Hz, 2H), 3.11–3.15 (m, 2H), 2.35 (s, 3H), 1.59–1.44 (m, 4H), 0.95 (t, J = 7.1 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 146.23, 143.06, 141.79, 135.83, 131.99, 129.59, 126.30, 125.31, 122.99, 122.37, 120.14, 117.51, 111.20, 110.24, 45.80, 32.17, 24.81, 23.10, 21.57, 13.87; EI-MS (m/z): 367 (M⁺); HRMS (EI) calcd for C₂₂H₂₅NO₂S (M⁺) 367.1606, found: 367.1601.

3-Allyl-2-butyl-5-fluoro-1-(methylsulfonyl)-1H-indole (2j). Colourless oil (113.9 mg, yield 92%). ¹H NMR (400 MHz, CDCl₃) δ 7.95 (dd, J = 9.1, 4.5 Hz, 1H), 7.16–7.10 (m, 1H), 7.02–6.96 (m, 1H), 5.96–5.85 (m, 1H), 5.11–5.03 (m, 2H), 3.42–3.37 (m, 2H), 2.95–2.89 (m, 5H), 1.67–1.61 (m, 2H), 1.44–1.37 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 160.03 (d, J_C–F = 240.6 Hz), 140.35, 135.26, 132.64, 132.06 (d, J_C–F = 9.6 Hz), 118.16 (d, J_C–F = 3.8 Hz), 116.19, 115.74 (d, J_C–F = 9.2 Hz), 111.90 (d, J_C–F = 25.0 Hz), 104.90 (d, J_C–F = 23.9 Hz), 39.99, 32.87, 28.67, 26.12, 22.83, 13.92; EI-MS (m/z): 309 (M⁺); HRMS (EI) calcd for C₁₆H₂₀FNO₂S (M⁺) 309.1199, found: 309.1197.

1-Allyl-2-butyl-5-fluoro-3-(methylsulfonyl)-1H-indole (3j). Pale yellow solid (100.2 mg, yield 81%), mp 81–82 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.69–7.62 (m, 1H), 7.21 (dd, J = 9.0, 4.3 Hz, 1H), 7.02–6.95 (m, 1H), 5.98–5.87 (m, 1H), 5.22 (dd, J = 10.4, 0.7 Hz, 1H), 4.89 (dd, J = 17.1, 0.7 Hz, 1H), 4.77–4.73 (m, 2H), 3.11–3.06 (m, 5H), 1.67–1.60 (m, 2H), 1.50–1.43 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 159.34 (d, J_C–F = 238.4 Hz), 147.57, 132.26, 131.77, 125.79 (d, J_C–F = 11.0 Hz), 117.76, 111.54 (d, J_C–F = 26.2 Hz), 111.35 (d, J_C–F = 9.6 Hz), 110.48 (d, J_C–F = 4.1 Hz), 105.26 (d, J_C–F = 25.9 Hz), 46.02, 45.91, 32.39, 24.64, 22.94, 13.84; EI-MS (m/z): 309 (M⁺); HRMS (EI) calcd for C₁₆H₂₀FNO₂S (M⁺) 309.1199, found: 309.1203.

3-Allyl-2-butyl-5-chloro-1-(methylsulfonyl)-1H-indole (2k). Yellow oil (117.3 mg, yield 90%). ¹H NMR (400 MHz, CDCl₃) δ 7.95–7.90 (m, 1H), 7.46–7.43 (m, 1H), 7.23 (dd, J = 8.9, 2.1 Hz, 1H), 5.97–5.83 (m, 1H), 5.16–4.94 (m, 2H), 3.48–3.30 (m, 2H), 2.96–2.87 (m, 5H), 1.67–1.60 (m, 2H), 1.45–1.36 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 140.05, 135.22, 134.73, 132.12, 129.54, 124.36, 118.81, 117.63, 116.24, 115.66, 40.21, 32.84, 28.53, 26.03, 22.82, 13.92; EI-MS (m/z): 327 (M⁺, (Cl³⁷)), 325 (M⁺, (Cl³⁵)); HRMS (EI) calcd for C₁₆H₂₀ClNO₂S (M⁺) 325.0903, found: 325.0905.

1-Allyl-2-butyl-5-chloro-3-(methylsulfonyl)-1H-indole (3k). Pale yellow solid (112.1 mg, yield 86%), mp 93–94 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.99 (dd, J = 1.6, 0.9 Hz, 1H), 7.24–7.19 (m, 2H), 5.97–5.88 (m, 1H), 5.23 (d, J = 10.9 Hz, 1H), 4.89 (d, J = 16.7 Hz, 1H), 4.76–4.73 (m, 2H), 3.11–3.08 (m, 5H), 1.68–1.63 (m, 2H), 1.52–1.44 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 147.44, 134.25, 131.65, 128.49, 126.18, 123.66, 119.33, 117.86, 111.48, 110.26, 46.04, 45.98, 32.43, 24.60, 22.98, 13.88; EI-MS (m/z): 327 (M⁺, (Cl³⁷)), 325 (M⁺, (Cl³⁵)); HRMS (EI) calcd for C₁₆H₂₀ClNO₂S (M⁺) 325.0903, found: 325.0907.

3-Allyl-6-bromo-2-butyl-1-(methylsulfonyl)-1H-indole (2l). Gray solid (131.8 mg, yield 89%), mp 62–63 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.89 (d, J = 8.9 Hz, 1H), 7.59 (d, J = 2.0 Hz, 1H), 7.37 (dd, J = 8.8, 2.0 Hz, 1H), 5.97–5.85 (m, 1H), 5.11–5.01 (m, 2H), 3.41–3.37 (m, 2H), 2.95–2.89 (m, 5H), 1.66–1.61 (m, 2H), 1.43–1.37 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 139.95, 135.21, 135.15, 132.62, 127.09, 121.88, 117.54, 117.27, 116.28, 116.08, 40.25, 32.87, 28.52, 26.03, 22.84, 13.94; EI-MS (m/z): 371 (M⁺, (Br⁸¹)), 369 (M⁺, (Br⁷⁹)); HRMS (EI) calcd for C₁₆H₂₀BrNO₂S (M⁺) 369.0398, found: 369.0403.

1-Allyl-6-bromo-2-butyl-3-(methylsulfonyl)-1H-indole (3l). Gray solid (122.9 mg, yield 83%), mp 113–114 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.14 (d, J = 1.9 Hz, 1H), 7.34 (dd, J = 8.7, 1.9 Hz, 1H), 7.16 (d, J = 8.7 Hz, 1H), 5.97–5.86 (m, 1H), 5.22 (d, J = 10.4 Hz, 1H), 4.87 (d, J = 17.1 Hz, 1H), 4.75–4.72 (m, 2H), 3.11–3.07 (m, 5H), 1.67–1.60 (m, 2H), 1.51–1.44 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 147.31, 134.55, 131.60, 126.69, 126.24, 122.26, 117.82, 116.03, 111.88, 110.13, 46.05, 45.94, 32.38, 24.54, 22.95, 13.86; EI-MS (m/z): 371 (M⁺, (Br⁸¹)), 369 (M⁺, (Br⁷⁹)); HRMS (EI) calcd for C₁₆H₂₀BrNO₂S (M⁺) 369.0398, found: 369.0395.

3-Allyl-2-butyl-6-methyl-1-(methylsulfonyl)-1H-indole (2m). Brown solid (110.0 mg, yield 90%), mp 43–44 °C. ¹H NMR (400 MHz, CDCl₃) δ 7.84 (s, 1H), 7.36 (d, J = 7.9 Hz, 1H), 7.10 (d, J = 7.9 Hz, 1H), 5.98–5.86 (m, 1H), 5.13–4.98 (m, 2H), 3.46–3.37 (m, 2H), 2.95–2.88 (m, 5H), 2.48 (s, 3H), 1.67–1.60 (m, 2H), 1.44–1.36 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 137.82, 136.84, 135.80, 134.43, 128.60, 125.06, 118.74, 118.23, 115.79, 114.90, 39.77, 32.93, 28.74, 26.02, 22.81, 22.02, 13.97; EI-MS (m/z): 305 (M⁺); HRMS (EI) calcd for C₁₇H₂₃NO₂S (M⁺) 305.1449, found: 305.1446.

1-Allyl-2-butyl-6-methyl-3-(methylsulfonyl)-1H-indole (3m). Yellow oil (106.3 mg, yield 87%). ¹H NMR (400 MHz, CDCl₃) δ 7.85 (d, J = 8.9 Hz, 1H), 7.12–7.07 (m, 2H), 5.99–5.90 (m, 1H), 5.21 (d, J = 11.0 Hz, 1H), 4.90 (d, J = 17.2 Hz, 1H), 4.74–4.71 (m, 2H), 3.12–3.08 (m, 5H), 2.47 (s, 3H), 1.67–1.60 (m, 2H), 1.50–1.45 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 145.63, 136.19, 133.20, 132.07, 124.05, 122.91, 119.25, 117.41, 110.30, 110.08, 45.90, 45.62, 32.49, 24.37, 22.90, 21.86, 13.85; EI-MS (m/z): 305 (M⁺); HRMS (EI) calcd for C₁₇H₂₃NO₂S (M⁺) 305.1449, found: 305.1448.

3-Allyl-2-butyl-1-(methylsulfonyl)-1H-indole-5-carbonitrile (2n). Brown solid (108.8 mg, yield 86%), mp 66–68 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.11–8.09 (m, 1H), 7.80 (d, J = 1.1 Hz, 1H), 7.51 (dd, J = 8.7, 1.6 Hz, 1H), 5.99–5.83 (m, 1H), 5.16–4.98 (m, 2H), 3.46–3.41 (m, 2H), 3.04 (s, 3H), 2.99–2.86 (m, 2H), 1.68–1.60 (m, 2H), 1.45–1.36 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 140.87, 138.11, 134.91, 130.74, 127.28, 123.90, 119.58, 117.39, 116.60, 115.20, 107.05, 41.14, 32.80, 28.41, 25.92, 22.81, 13.85; EI-MS (m/z): 316 (M⁺); HRMS (EI) calcd for C₁₇H₂₀N₂O₂S (M⁺) 316.1245, found: 316.1243.

1-Allyl-2-butyl-3-(methylsulfonyl)-1H-indole-5-carbonitrile (3n). Yellow oil (97.5 mg, yield 77%). ¹H NMR (400 MHz, CDCl₃) δ 8.35–8.30 (m, 1H), 7.47 (dd, J = 8.6, 1.5 Hz, 1H), 7.37 (d, J = 8.4 Hz, 1H), 6.00–5.88 (m, 1H), 5.25 (d, J = 10.4 Hz, 1H), 4.87 (d, J = 17.1 Hz, 1H), 4.82–4.78 (m, 2H), 3.14–3.07 (m, 5H), 1.69–1.60 (m, 2H), 1.52–1.44 (m, 2H), 0.95 (t, J = 7.3 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 148.85, 137.47, 131.20, 126.23, 125.01, 124.98, 119.78, 118.15, 111.50, 111.47, 105.82, 46.17, 46.11, 32.26, 24.57, 22.94, 13.79; EI-MS (m/z): 316 (M⁺); HRMS (EI) calcd for C₁₇H₂₀N₂O₂S (M⁺) 316.1245, found: 316.1248.

3-Allyl-2-butyl-1-(methylsulfonyl)-5-(trifluoromethyl)-1H-indole (2o). Yellow solid (126.5 mg, yield 88%), mp 72–73 °C. ¹H NMR (300 MHz, CDCl₃) δ 8.12 (d, J = 8.8 Hz, 1H), 7.74 (s, 1H), 7.52 (d, J = 8.7 Hz, 1H), 6.01–5.86 (m, 1H), 5.18–4.98 (m, 2H), 3.46 (d, J = 5.9 Hz, 2H), 3.06–2.90 (m, 5H), 1.71–1.59 (m, 2H), 1.48–1.35 (m, 2H), 0.95 (t, J = 7.3 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 140.45, 137.94, 135.18, 130.56, 126.10 (q, J_C–F = 32.2 Hz), 124.72 (q, J_C–F = 271.9 Hz), 121.03 (q, J_C–F = 3.3 Hz), 118.02, 116.48 (q, J_C–F = 3.9 Hz), 116.35, 114.81, 40.70, 32.87, 28.47, 26.02, 22.86, 13.91; EI-MS (m/z): 359 (M⁺); HRMS (EI) calcd for C₁₇H₂₀F₃NO₂S (M⁺) 359.1167, found: 359.1169.

1-Allyl-2-butyl-3-(methylsulfonyl)-5-(trifluoromethyl)-1H-indole (3o). White solid (119.3 mg, yield 83%), mp 89–90 °C. ¹H NMR (300 MHz, CDCl₃) δ 8.29 (s, 1H), 7.49 (d, J = 8.6 Hz, 1H), 7.38 (d, J = 8.7 Hz, 1H), 6.03–5.86 (m, 1H), 5.24 (d, J = 10.4 Hz, 1H), 4.88 (d, J = 17.2 Hz, 1H), 4.80 (d, J = 2.9 Hz, 2H), 3.22–3.06 (m, 5H), 1.69–1.62 (m, 2H), 1.54–1.43 (m, 2H), 0.96 (t, J = 7.2 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) δ 148.25, 137.25, 131.45, 124.88 (q, J_C–F = 272.1 Hz), 124.87 (q, J_C–F = 32.2 Hz), 124.65, 120.05 (q, J_C–F = 3.4 Hz), 117.92, 117.45 (q, J_C–F = 4.0 Hz), 111.48, 110.88, 46.14, 46.02, 32.35, 24.57, 22.94, 13.81; EI-MS (m/z): 359 (M⁺); HRMS (EI) calcd for C₁₇H₂₀F₃NO₂S (M⁺) 359.1167, found: 359.1162.

Acknowledgements

We gratefully acknowledge financial support from the National Natural Science Foundation of China (Grants 21021063, 91229204, and 81025017), National S&T Major Projects (2012ZX09103101-072, 2012ZX09301001-005, 2013ZX09507-001, and 2014ZX09507002-001) and Chengdu University New Faculty Start-up Funding (No. 2081915037).

Notes and references

1. (a) A. Grossmann, S. Bartlett, M. Janecek, J. T. Hodgkinson and D. R. Spring, Angew. Chem., Int. Ed., 2014, 53, 13093; (b) R. A. Stavenger and S. L. Schreiber, Angew. Chem., Int. Ed., 2001, 40, 3417; (c) W. Liu, V. Khedkar, B. Baskar, M. Schürmann and K. Kumar, Angew. Chem., Int. Ed., 2011, 50, 6900; (d) B. Jiang, W.-J. Hao, X. Wang, F. Shi and S.-J. Tu, J. Comb. Chem., 2009, 11, 846; (e) N. Gigant, E. Claveau, P. Bouyssou and I. Gillaizeau, Org. Lett., 2012, 14, 844; (f) E. Lenci, G. Menchi, A. Guarna and A. Trabocchi, J. Org. Chem., 2015, 80, 2182; (g) H. Kim, T. T. Tung and S. B. Park, Org. Lett., 2013, 15, 5814; (h) A. Kumar, G. Gupta and S. Srivastava, J. Comb. Chem., 2010, 12, 458.
2. (a) Z.-C. Geng, S.-Y. Zhang, N.-K. Li, N. Li, J. Chen, H.-Y. Li and X.-W. Wang, J. Org. Chem., 2014, 79, 10772; (b) O. Sangmi, J. J. Hwan, K. K. Sung, K. Yeonjin and B. P. Seung, J. Comb. Chem., 2010, 12, 548; (c) O. Kwon, S. B. Park and S. L. Schreiber, J. Am. Chem. Soc., 2002, 124, 13402; (d) H. Oguri and S. L. Schreiber, Org. Lett., 2005, 7, 47; (e) J. K. Sello, P. R. Andreana, D. Lee and S. L. Schreiber, Org. Lett., 2003, 5, 4125; (f) D. Lee, J. K. Sello and S. L. Schreiber, Org. Lett., 2000, 2, 709; (g) W. Tan, X.-T. Zhu, S. Zhang, G.-J. Xing, R.-Y. Zhu and F. Shi, RSC Adv., 2013, 3, 10875; (h) J. Mahatthananchai, A. M. Dumas and J. W. Bode, Angew. Chem., Int. Ed., 2012, 51, 10954.
3. (a) A. Kumar, S. Srivastava, G. Gupta, V. Chaturvedi, S. Sinha and R. Srivastava, ACS Comb. Sci., 2011, 13, 65; (b) S. Dandapani, A. R. Germain, I. Jewett, S. L. Quement, J. C. Marie, G. Muncipinto, J. R. Duvall, L. C. Carmody, J. R. Perez, J. C. Engel, J. Gut, D. Kellar, J. L. Siqueira-Neto, J. H. McKerrow, M. Kaiser, A. Rodriguez, M. A. Palmer, M. Foley, S. L. Schreiber and B. Munoz, ACS Med. Chem. Lett., 2014, 5, 149; (c) G. L. Thomas, R. J. Spandl, F. G. Glansdorp, M. Welch, A. Bender, J. Cockfield, J. A. Lindsay, C. Bryant, D. F. Brown, O. Loiseleur, H. Rudyk, M. Ladlow and D. R. Spring, Angew. Chem., Int. Ed., 2008, 47, 2808; (d) W. R. Galloway, A. Bender, M. Welch and D. R. Spring, Chem. Commun., 2009, 18, 2446.
4. S. Marcaccini and T. Torroba, in Multicomponent Reactions, ed. J. Zhu and H. Bienaymé, Wiley-VCH, Weinheim, 2005, pp. 33–75.
5. N. A. Afagh and A. K. Yudin, Angew. Chem., Int. Ed., 2010, 49, 262.
6. (a) G. Cuny, M. Bois-Choussy and J. Zhu, J. Am. Chem. Soc., 2004, 126, 14475; (b) W. Erb, L. Neuville and J. Zhu, J. Org. Chem., 2009, 74, 3109.
7. (a) Q. Cheng, J. Zhao, Y. Ishikawa, N. Asao, Y. Yamamoto and T. Jin, Org. Lett., 2013, 15, 5766; (b) T. Fujihara, Y. Katafuchi, T. Iwai, J. Terao and Y. Tsuji, J. Am. Chem. Soc., 2010, 132, 2094; (c) M. Suginome, M. Shirakura and A. Yamamoto, J. Am. Chem. Soc., 2006, 128, 14438; (d) T. Ishiyama, N. Matsuda, N. Miyaura and A. Suzuki, J. Am. Chem. Soc., 1993, 115, 11018; (e) N. Iwadate and M. Suginome, J. Am. Chem. Soc., 2010, 132, 2548; (f) P. Schreyer, P. Paetzold and R. Boese, Chem. Ber., 1988, 121, 195; (g) H. Braunschweig, A. Damme, J. O. Jimenez-Halla, B. Pfaffinger, K. Radacki and J. Wolf, Angew. Chem., Int. Ed., 2012, 51, 10034; (h) M. Suginome, H. Nakamura and Y. Ito, Chem. Commun., 1996, 2777; (i) M. Suginome, H. Nakamura and Y. Ito, Angew. Chem., Int. Ed., 1997, 36, 2516; (j) T. Ohmura, K. Oshima and M. Suginome, Chem. Commun., 2008, 1416; (k) T. Ohmura, K. Oshima, H. Taniguchi and M. Suginome, J. Am. Chem. Soc., 2010, 132, 12194; (l) T. Ishiyama, K. Nishijima, N. Miyaura and A. Suzuki, J. Am. Chem. Soc., 1993, 115, 7219; (m) M. F. Lappert and B. Prokai, J. Organomet. Chem., 1964, 1, 384; (n) S. Hara, H. Dojo, S. Takinami and A. Suzuki, Tetrahedron Lett., 1983, 24, 731; (o) S. Onozawa, Y. Hatanaka, T. Sakakura, S. Shimada and M. Tanaka, Organometallics, 1996, 15, 5450.
8. (a) T. Shimada, I. Nakamura and Y. Yamamoto, J. Am. Chem. Soc., 2004, 126, 10546; (b) C.-Y. Wu, M. Hu, Y. Liu, R.-J. Song, Y. Lei, B.-X. Tang, R.-J. Li and J.-H. Li, Chem. Commun., 2012, 48, 3197; (c) F. Zhao, D.-Y. Zhang, Y. Nian, L. Zhang, W. Yang and H. Liu, Org. Lett., 2014, 16, 5124; (d) C.-L. Wu, F. Zhao, S.-J. Shu, J. Wang and H. Liu, RSC Adv., 2015, 5, 90396; (e) X.-M. Zeng, R. Kinjo, B. Donnadieu and G. Bertrand, Angew. Chem., Int. Ed., 2010, 49, 942; (f) I. Nakamura, U. Yamagishi, D. Song, S. Konta and Y. Yamamoto, Angew. Chem., Int. Ed., 2007, 46, 2284; (g) I. Nakamura, Y. Sato, S. Konta and M. Terada, Tetrahedron Lett., 2009, 50, 2075; (h) I. Nakamura, U. Yamagishi, D. Song, S. Konta and Y. Yamamoto, Chem.–Asian J., 2008, 3, 285; (i) S. Cacchi, G. Fabrizi and P. Pace, J. Org. Chem., 1998, 63, 1001; (j) Y. D. Dhage, T. Shirai, M. Arima, A. Nakazima, H. Hikawa, I. A. T. Kusakabe, K. Takahashi and K. Kato, RSC Adv., 2015, 5, 42623; (k) S. Kamijo and Y. Yamamoto, J. Am. Chem. Soc., 2002, 124, 11940; (l) P.-Y. Chiang, Y.-C. Lin, Y. Wang and Y.-H. Liu, Organometallics, 2010, 29, 5776; (m) K. C. Majumdar, S. Hazra and B. Roy, Tetrahedron Lett., 2001, 52, 6697; (n) E. Chong and S. A. Blum, J. Am. Chem. Soc., 2015, 137, 10144.
9. (a) I. Nakamura, Y. Mizushima, I. D. Gridnev and Y. Yamamoto, J. Am. Chem. Soc., 2005, 127, 9844; (b) I. Nakamura, G. B. Bajracharya, H. Y. Wu, K. Oishi, Y. Mizushima, I. D. Gridnev and Y. Yamamoto, J. Am. Chem. Soc., 2004, 126, 15423.
10. C.-D. Wang, Y. F. Hsieh and R. S. Liu, Adv. Synth. Catal., 2014, 356, 144.
11. (a) I. Nakamura, Y. Mizushima and Y. Yamamoto, J. Am. Chem. Soc., 2005, 127, 15022; (b) J. J. Hirner, D. J. Faizi and S. A. Blum, J. Am. Chem. Soc., 2014, 136, 4740; (c) A. Fürstner and P. W. Davies, J. Am. Chem. Soc., 2005, 127, 15024; (d) Z.-Q. Liang, S.-M. Ma, J.-H. Yu and R.-R. Xu, J. Org. Chem., 2007, 72, 9219; (e) S. Cacchi, G. Fabrizi and L. Moro, Tetrahedron Lett., 1998, 39, 5101.
12. (a) Q.-W. Zhang, K. An and W. He, Angew. Chem., Int. Ed., 2014, 53, 5667; (b) I. Nakamura, T. Sato, M. Terada and Y. Yamamoto, Org. Lett., 2008, 10, 2649; (c) I. Nakamura, T. Sato, M. Terada and Y. Yamamoto, Org. Lett., 2007, 9, 4081.
13. T. Matsuda and Y. Ichioka, Org. Biomol. Chem., 2012, 10, 3175.
14. (a) Y. Kobayashi, H. Kamisaki, K. Yanada, R. Yanada and Y. Takemoto, Tetrahedron Lett., 2005, 46, 7549; (b) Y. Kobayashi, H. Kamisaki, R. Yanada and Y. Takemoto, Org. Lett., 2006, 8, 2711; (c) M. R. Fielding, R. Grigg and C. J. Urch, Chem. Commun., 2000, 22, 2239.
15. K. N. Tu, J. J. Hirner and S. A. Blum, Org. Lett., 2016, 18, 480.
16. T. Iwai, T. Fujihara, J. Terao and Y. Tsuji, J. Am. Chem. Soc., 2009, 131, 6668.
17. W. T. Teo, W.-D. Rao, M. J. Koh and P. W. H. Chan, J. Org. Chem., 2013, 78, 7508.
18. M. Toyofuku, S. Fujiwara, T. Shinike, H. Kuniyasu and N. Kambe, J. Am. Chem. Soc., 2005, 127, 9706.
19. (a) M. Suginome, A. Yamamoto and M. Murakami, J. Am. Chem. Soc., 2003, 125, 6358; (b) A. Yamamoto and M. Suginome, J. Am. Chem. Soc., 2005, 127, 15706; (c) M. Daini, A. Yamamoto and M. Suginome, J. Am. Chem. Soc., 2008, 130, 2918.
20. For representative literatures on the migration of sulfonyl group, see: (a) X.-Y. Xin, D.-P. Wang, X.-C. Li and B.-S. Wan, Angew. Chem., Int. Ed., 2012, 51, 1693; (b) B. Prasad, R. Adepu, S. Sandra, D. Rambabu, G. R. Krishna, C. M. Reddy, G. S. Deora, P. Misraa and M. Pal, Chem. Commun., 2012, 48, 10434; (c) X.-C. Hong, J. M. Mejía-Oneto, S. France and A. Padwa, Tetrahedron Lett., 2006, 47, 2409.

---

Footnotes

† Electronic supplementary information (ESI) available: Experimental details and additional spectra. See DOI: 10.1039/c6ra15945a

‡ These authors contributed equally.

---