Indium chloride catalyzed three-component reaction for the synthesis of 2-((oxoindolin-3-yl)-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamides

Abstract

In the presence of indium chloride as a Lewis acid catalyst, the three-component reaction of benzohydrazide, cyclic diketones and 3-phenacylideneoxindoles in refluxing acetonitrile afforded functionalized 2-((oxoindolin-3-yl)-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamides in satisfactory yields. Under similar conditions, the reaction with 2-hydroxybenzohydrazide and picolinohydrazide also resulted in corresponding functionalized 2-((oxoindolin-3-yl)-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamides in high yields. The ¹H and ¹³C NMR spectra indicated that the obtained products exist in both a keto-form and an enol-form.

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Introduction

β-Enaminone and its ester as well as amide derivatives represent one of the most important synthetic building blocks possessing multiple reactive sites and have been widely used for the synthesis of a widely variety of heterocycles and pharmaceutical compounds.^1,2 β-Enaminone combined the nucleophilic enamine and the electrophilic enone (ester, amide) moieties into one molecule, which have a high tendency to perform cyclization by using the C=C double bond between the C2 and C3 positions. The terminal carbonyl group and amino groups also underwent a sequential annulation process.^3,4 Traditionally, β-enaminones were readily prepared by the direct condensation of various β-dicarbonyl compounds with primary and secondary amines.⁵ On the other hand, the addition of aliphatic and aromatic amines to the electron-deficient alkynes having carbonyl groups was also a convenient method for preparation of β-enaminones and β-enamino esters.⁶ In recent years, β-enaminones were also employed as key reactants in many domino and multicomponent reactions due to its easily formation and structural diversity.^7–11 We envisioned that the analogs of β-enaminones, which were generated from the other nitrogen-containing nucleophiles such as hydrazine, hydroxylamine, isocyanide, might have versatile reactivity and very important applications in organic reactions. A literature survey indicated that the reactive reagents derived from the condensation reaction of benzohydrazide with cyclic dicarbonyl compounds showed similar reactivity to that of β-enaminones and have been used to synthesize various hetrocycles.^12,13 In order to explore the potential applications of β-enaminone analogs and with the aim of expanding our previous studies on the developing efficient synthetic procedures for nitrogen-containing heterocycles,^14,15 herein we wish to report the three-component reaction of benzohydrazide, cyclic diketones and 3-phenacylideneoxindoles for the efficient preparing functionalized 2-((oxoindolin-3-yl)-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamides.

Results and discussions

We initiated our investigation by examining the reaction conditions of three-component reaction. It has been reported that the reaction of cyclic β-enaminones with 3-phenacylideneoxindoles or 3-cyanomethylidene-2-oxindoles in basic media afforded functionalized indolo[2,3-b]quinolines^16a and spiro[indoline-3,4′-quinoline].^16b During this project, we found that the three-component reaction of benzohydrazide, cyclohexane-1,3-dione and 1-benzyl-5-methyl-3-(2-oxo-2-(p-tolyl)ethylidene)indolin-2-one did not occur in ethanol without catalyst and with Et₃N, DABCO, Cs₂CO₃ as base promoter both at room temperature and under refluxing conditions (Table 1). When various acid promoters was employed, instead of giving the expected indolo[2,3-b]quinolines^16a and spiro[indoline-3,4′-quinoline],^16b the reaction proceeded smoothly to give N-(3-(1-benzyl-5-methyl-2-oxoindolin-3-yl)-4-oxo-2-(p-tolyl)-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamide 1a as main product. Bronsted acid such as p-TsOH, HCl, HOAc, L-proline afforded the product 1a in lower to moderate yields. Lewis acid BF₃·Et₂O, TiCl₄, BiCl₃ and In(OTf)₃ also have effective catalytic ability. When Lewis acid InCl₃ was used in refluxing ethanol, the product was 1a was obtained in 65% yield. Further, the highest yield of product 1a was achieved by carrying out the reaction in refluxing acetonitrile with a catalytic amount of InCl₃. Indium chloride is an attractive reagent and has been used in various organic reactions because it exhibit mild Lewis acidity and is stable against aqueous media. We were pleased to find that indium chloride is the effective catalyst for this three-component reaction.

Table 1 Optimization of the reaction conditions for three-component reaction^a

Entry	Catalyst	Solvent	Temp	Time	Yield^b (%)
a Reactions were performed with benzohydrazide (0.50 mmol), cyclohexane-1,3-dione (0.5 mmol), 1-benzyl-5-methyl-3-(2-oxo-2-(p-tolyl)ethylidene)indolin-2-one (0.3 mmol), acid or base (0.5 mmol), solvent (10.0 mL).b Isolated yield.c InCl3·4H2O (0.2 mmol) was used.
1	—	EtOH	rt	8	—
2	Et3N	EtOH	Reflux	8	—
3	DABCO	EtOH	Reflux	8	—
4	Cs2CO3	EtOH	Reflux	8	—
5	p-TsOH	EtOH	Reflux	8	50
6	HCl	EtOH	Reflux	8	20
7	HOAc	EtOH	Reflux	8	10
8	L-Proline	EtOH	Reflux	8	35
9	InCl3·4H2O	CH3CN	rt	12	—
10	InCl3·4H2O	EtOH	Reflux	8	65
11	InCl3·4H2O	CH3CN	Reflux	8	81
12	InCl3·4H2O	CH3CN	Reflux	8	80^c
13	TiCl4	CH3CN	Reflux	8	40
14	BF3·Et2O	CH3CN	Reflux	8	10
15	BiCl3	CH3CN	Reflux	8	28
16	In(OTf)3	CH3CN	Reflux	8	52

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With the optimized reaction conditions in hand, we next investigated the substrate scope of the three-component reaction. Cylohexane-1,3-dione and dimedone were successfully employed in the reaction. In general, most of the reactions proceeded well to afford the desired products in satisfactory yields (Table 2). The substituents on the 3-phenacylideneoxindoles showed very little effect on the yields. The structures of the obtained products 1a–1n were established on the IR, HRMS, ¹H and ¹³C NMR spectra. ¹H NMR spectra clearly indicated the products 1a–1n have two isomers with molecular ratios in the range of 57 : 43 to 73 : 23, which is due to the tautomerization equilibrium between the keto-form and enol-form existing in common 3-substituted oxindoles.^17,18 The single crystal structures of the compounds 1c and 1g were successfully determined by X-ray diffraction method (Fig. 1 and 2). It can be seen that the molecule exists in keto-from in solid state.

Table 2 Three-component reaction for 4,5,6,7-tetrahydro-1H-indol-1-ylbenzamides 1a–1n^a

Entry	Compd	R	R′	R′′	Ar	Yield^b^c (%, keto/enol)
a Reactions were performed with benzohydrazide (0.50 mmol), cyclic diketone (0.5 mmol), 3-phenacylideneoxindole (0.3 mmol), indium chloride (0.2 mmol), CH3CN (10.0 mL), reflux, 8 h.b Isolated yields based on 3-phenacylideneoxindole.c Ratio of keto/enol forms is determined by ^1H NMR spectra.
1	1a	H	CH3	Bn	p-CH3C6H4	80 (65 : 35)
2	1b	H	Cl	Bn	p-CH3C6H4	69 (74 : 26)
3	1c	H	Cl	Bn	p-OCH3C6H4	75 (72 : 28)
4	1d	H	F	Bn	p-CH3C6H4	70 (71 : 29)
5	1e	CH3	H	Bn	p-ClC6H4	88 (60 : 40)
6	1f	CH3	CH3	n-Bu	p-OCH3C6H4	65 (63 : 37)
7	1g	CH3	CH3	Bn	p-ClC6H4	85 (51 : 49)
8	1h	CH3	Cl	Bn	C6H5	70 (70 : 30)
9	1i	CH3	Cl	Bn	p-CH3C6H4	72 (77 : 23)
10	1j	CH3	Cl	Bn	p-OCH3C6H4	83 (75 : 25)
11	1k	CH3	Cl	n-Bu	p-OCH3C6H4	80 (65 : 35)
12	1l	CH3	F	Bn	p-CH3C6H4	75 (70 : 30)
13	1m	CH3	F	n-Bu	p-OCH3C6H4	73 (63 : 37)
14	1n	CH3	F	Bn	p-ClC6H4	83 (57 : 43)

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Fig. 1 Single crystal structure of compound 1c.

Fig. 2 Single crystal structure of compound 1g.

Encouraged by the above results, 2-hydroxybenzohydrazide and 2-picolinohydrazide were also employed in the three-component reaction. The results are summarized in Table 3. It can be seen that the hydroxyl and pyridyl groups did not take part in the reaction. The functionalized 4,5,6,7-(tetrahydro-1H-indol-1-yl)benzamides 2a–2i and 3a–3d were produced in good yields. Similarly, ¹H NMR spectra that a mixture of keto-form and enol-form with a ratio of about 7 : 3 was observed in the all products. The ¹³C NMR spectra also displayed the corresponding signs of both keto-form and enol-form. The keto-form exist in the single crystal structures of compound 2d and 3c (Fig. 3 and 4), which also indicated that the keto-form is stable than enol-form.

Table 3 Synthesis for 4,5,6,7-(tetrahydro-1H-indol-1-yl)benzamides 2a–2i and 3a–3d^a

Entry	Compd	R	R′	R′′	Ar	Yield^b (%)
a Reactions were performed with 2-hydroxybenzohydrazide, or picolinohydrazide (0.50 mmol), cyclic diketone (0.5 mmol), 3-phenacyllicendeoxindole (0.3 mmol), indium chloride (0.2 mmol), CH3CN (10.0 mL), reflux, 8 h.b Isolated yields based on 3-phenacylideneoxindole.
1	2a	H	Cl	Bn	p-CH3C6H4	65 (79 : 21)
2	2b	H	Cl	Bn	p-OCH3C6H4	78 (78 : 22)
3	2c	H	F	Bn	p-CH3C6H4	70 (76 : 24)
4	2d	H	F	n-Bu	p-OCH3C6H4	80 (68 : 32)
5	2e	CH3	Cl	Bn	p-CH3C6H4	72 (79 : 21)
6	2f	CH3	Cl	Bn	p-OCH3C6H4	83 (76 : 24)
7	2g	CH3	Cl	n-Bu	p-OCH3C6H4	81 (70 : 30)
8	2h	CH3	F	Bn	p-CH3C6H4	75 (76 : 24)
9	2i	CH3	F	n-Bu	p-OCH3C6H4	73 (67 : 33)
10	3a	CH3	CH3	Bn	p-CH3C6H4	56 (69 : 31)
11	3b	CH3	CH3	n-Bu	p-OCH3C6H4	70 (69 : 31)
12	3c	CH3	Cl	Bn	p-OCH3C6H4	60 (75 : 25)
13	3d	CH3	Cl	n-Bu	p-OCH3C6H4	68 (67 : 33)

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Fig. 3 Single crystal structure of compound 2d.

Fig. 4 Single crystal structure of compound 3c.

In order to explain the formation of 4,5,6,7-(tetrahydro-1H-indol-1-yl)benzamides, a concise reaction mechanism was proposed on the basis of the previously reported reactions of β-enaminones (Scheme 1).¹⁸ As an effective Lewis acid catalyst, indium chloride activated the carbonyl group of dimedone to react with benzohydrazide to form a reactive intermediate (A), which is very similar to the β-enaminones. Secondly, Michael addition of intermediate (A) to the 3-phenacylideneoxindole could proceed according to two different routes. On the path a, addition of intermediate (A) at the exocyclic carbon atom of 3-phenacylideneoxindole afforded a adduct intermediate (B). Then, intramolecular condensation of hydrazide with carbonyl group produced the obtained product 1 with elimination of water. Because there is one active proton on the carbon atom at 3-position of oxindole moiety, the product 1 has a tautomerization equilibrium between keto-form and enol-form. On the path b, the Michael addition of intermediate (A) to the carbon atom at 3-position of 3-phenacylidenoxindole would produce another adduct (B′).^16b The sequential cyclization reaction could give spiro[indoline-3,4′-quinoline] derivatives (1′). It might be due to the relatively larger steric effect for the formation of intermediate (B′), the reaction proceeded according to the path a to give the polysubstituted pyrrole 1 as main product. It was not success for trying to get the spiro[indoline-3,4′-quinoline] derivatives by changing the reaction conditions.

Scheme 1 The proposed reaction mechanism for three-component reaction.

Conclusion

In summary, we have successfully developed a practical procedure for the efficient synthesis of functionalized 2-((oxoindolin-3-yl)-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamides from indium chloride catalyzed three-component reaction of benzohydrazide, cyclic diketones and 3-phenacylideneoxindoles. This reaction originated from the versatile reactivity of β-enaminones and explored potential synthetic applications of β-enaminone analogs in new multicomponent reaction. The advantages of this reaction included using readily available reagents, mild reaction conditions, widely variety of substrates, good yields and high regioselectivity. This reaction might be found potential applications for the synthesis of the nitrogen-containing heterocycles in synthetic and medicinal chemistry.

Experimental section

Typical procedure for the three-component reactions

A mixture of benzohydrazide, 2-hydroxybenzohydrazide, or 2-picolinohydrazide (0.50 mmol), cyclic diketone (0.5 mmol), 3-phenacylideneoxindole (0.3 mmol), and indium chloride (0.2 mmol) in acetonitrile (10.0 mL) was refluxed for eight hours. TLC monitor indicted that the reaction has finished. The solvent was removed by rotator evaporation at reduced pressure. The residue was subjected to preparative thin-layer chromatography with light petroleum and ethyl acetate (v/v = 1 : 1) as elute to give pure product for analysis.

N-(3-(1-Benzyl-5-methyl-2-oxoindolin-3-yl)-4-oxo-2-(p-tolyl)-4,5,6,7-tetrahydro-1H-indol-1-yl)benzamide (1a). White solid, 80%, mp 202–204 °C; ¹H NMR (600 MHz, CDCl₃) δ: keto-form: 10.19 (s, 1H, NH), 7.33 (d, J = 7.8 Hz, 2H, ArH), 7.40 (d, J = 7.8 Hz, 2H, ArH), 7.35–7.34 (m, 2H, ArH), 7.31 (t, J = 7.8 Hz, 1H, ArH), 7.26–7.24 (m, 1H, ArH), 7.20–7.14 (m, 4H, ArH), 7.01 (d, J = 7.2 Hz, 1H, ArH), 6.93–6.90 (m, 2H, ArH), 6.76 (d, J = 7.2 Hz, 1H, ArH), 6.60 (d, J = 7.8 Hz, 1H, ArH), 5.23 (d, J = 16.2 Hz, 1H, CH), 4.72 (d, J = 16.2 Hz, 1H, CH), 4.69 (s, 1H, CH), 2.68–2.60 (m, 3H, CH), 2.32 (s, 3H, CH₃), 2.30–2.29 (m, 1H, CH), 2.24 (s, 3H, CH₃), 2.04–2.00 (m, 1H, CH), 1.93 (s, 1H, CH); enol-form: 10.71 (s, 1H, NH), 7.60 (d, J = 7.8 Hz, 2H, ArH), 7.31 (d, J = 7.8 Hz, 1H, ArH), 6.54 (d, J = 7.2 Hz, 1H, ArH), 6.47 (d, J = 7.8 Hz, 1H, ArH), 6.04 (s, 1H, CH), 4.54 (d, J = 16.2 Hz, 1H, CH), 4.02 (d, J = 16.2 Hz, 1H, CH), 2.26–2.25 (m, 1H, CH), 2.28 (s, 3H, CH₃), 2.23 (s, 3H, CH₃), 2.20–2.19 (m, 1H, CH), 2.09 (s, 1H, CH); ratio of keto/enol forms = 0.65 : 0.35. ¹³C NMR (150 MHz, CDCl₃) δ: 195.9, 193.1, 177.8, 176.8, 166.9, 166.2, 145.8, 145.0, 141.8, 139.6, 138.2, 137.4, 136.7, 136.4, 135.6, 133.2, 133.0, 132.4, 132.2, 132.0, 131.4, 131.3, 131.1, 130.2, 130.1, 129.6, 129.3, 128.7, 128.5, 128.3, 128.2, 128.0, 127.8, 127.7, 127.6, 127.5, 127.4, 127.0, 126.9, 126.3, 125.9, 125.8, 124.3, 116.6, 115.7, 108.6, 44.8, 44.7, 43.9, 43.8, 38.8, 28.0, 23.0, 22.8, 21.4, 21.3, 21.2, 21.1, 21.0, 20.9; IR (KBr) ν: 3754, 3518, 3268, 3024, 2942, 2872, 1693, 1656, 1497, 1369, 1271, 1186, 1100, 1025, 978, 898, 857, 812, 731 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₈H₃₃N₃NaO₃ ([M + Na]⁺): 602.2414. Found: 602.2420.

N-(3-(1-Benzyl-5-chloro-2-oxoindolin-3-yl)-4-oxo-2-(p-tolyl)-4,5,6,7-tetrahydro-1H-indol-1-yl)-2-hydroxybenzamide (2a). White solid, 65%, mp 260–262 °C; ¹H NMR (600 MHz, DMSO-d₆) δ: keto-form: 11.43 (brs, 1H, NH), 11.21 (s, 1H, OH), 7.72–7.70 (m, 1H, ArH), 7.45–7.42 (m, 5H, ArH), 7.32 (t, J = 7.2 Hz, 2H, ArH), 7.29–7.24 (m, 3H, ArH), 7.20–7.19 (m, 1H, ArH), 6.97 (d, J = 8.4 Hz, 1H, ArH), 6.94–6.91 (m, 1H, ArH), 6.86–6.82 (m, 1H, ArH), 6.77–6.76 (m, 1H, ArH), 5.11–5.08 (m, 1H, CH), 4.75 (d, J = 16.2 Hz, 1H, CH), 4.66 (s, 1H, CH), 2.80–2.77 (m, 1H, CH), 2.69–2.62 (m, 1H, CH), 2.30 (s, 3H, CH₃), 2.28–2.17 (m, 2H, CH₂), 2.01 (s, 2H, CH₂); enol-form: 11.55 (brs, 1H, NH), 7.62–7.57 (m, 1H, ArH), 7.40–7.37 (m, 1H, ArH), 6.86–6.82 (m, 1H, ArH), 6.63–6.57 (m, 1H, ArH), 5.85 (s, 1H, CH), 4.56 (d, J = 16.2 Hz, 1H, CH), 4.39–4.31 (m, 1H, CH), 2.28–2.17 (m, 1H, CH), 2.08 (s, 3H, CH₃); ratio of keto/enol form = 0.79 : 0.21; ¹³C NMR (150 MHz, DMSO-d₆) δ: 190.7, 174.4, 165.4, 156.5, 144.2, 144.1, 142.2, 140.3, 136.8, 135.4, 134.8, 133.0, 132.9, 130.6, 128.6, 128.1, 127.4, 127.3, 126.2, 126.1, 126.0, 125.9, 124.8, 124.4, 124.3, 121.3, 118.1, 118.0, 115.9, 115.8, 114.7, 114.6, 113.8, 109.1, 109.1, 109.0, 42.7, 42.4, 36.4, 21.6, 21.5, 19.7, 19.6, 19.4; IR (KBr) ν: 3655, 3263, 3037, 2924, 1933, 1810, 1696, 1654, 1597, 1520, 1481, 1438, 1363, 1255, 1205, 1168, 1111, 1072, 1028, 974, 905, 868, 818, 757, 693 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₇H₃₁ClN₃O₄ ([M + H]⁺): 616.1998. Found: 616.1981.

N-(3-(1-Benzyl-5-methyl-2-oxoindolin-3-yl)-6,6-dimethyl-4-oxo-2-(p-tolyl)-4,5,6,7-tetrahydro-1H-indol-1-yl)picolinamide (3a). White solid, 56%, mp 290–292 °C; ¹H NMR (600 MHz, DMSO-d₆) δ: keto-form: 11.97 (brs, 1H, NH), 8.71–8.60 (m, 1H, ArH), 8.04–7.87 (m, 2H, ArH), 7.68–7.65 (m, 1H, ArH), 7.44 (s, 3H, ArH), 7.31–7.18 (m, 5H, ArH), 6.96–6.76 (m, 2H, ArH), 6.62 (brs, 1H, ArH), 5.09 (d, J = 15.0 Hz, 1H, CH), 4.70 (d, J = 16.2 Hz, 1H, CH), 4.53 (s, 1H, CH), 2.62–2.58 (m, 1H, CH), 2.41 (brs, 2H, CH₂), 2.27 (s, 3H, CH₃), 2.20 (s, 3H, CH₃), 2.09 (brs, 1H, CH), 1.02 (s, 3H, CH₃), 0.97 (s, 3H, CH₃); enol-form: 12.15 (brs, 1H, NH), 6.53 (brs, 1H, ArH), 5.74 (s, 1H, CH), 4.49 (brs, 1H, CH), 4.27 (brs, 1H, CH), 2.41–2.37 (m, 2H, CH₂), 2.26 (s, 3H, CH₃), 2.17 (s, 3H, CH₃), 1.16 (s, 3H, CH₃), 1.15 (s, 3H, CH₃); ratio of keto/enol forms = 0.69 : 0.31; ¹³C NMR (150 MHz, DMSO-d₆) δ: 193.5, 190.5, 175.3, 163.0, 148.4, 148.3, 147.4, 147.3, 143.5, 141.4, 139.6, 137.6, 137.2, 136.4, 135.9, 135.4, 129.7, 129.0, 128.6, 127.9, 127.1, 127.0, 126.9, 126.6, 126.5, 125.7, 125.3, 122.6, 122.4, 114.3, 113.6, 110.4, 107.9, 107.6, 59.2, 51.9, 51.1, 43.3, 42.9, 42.3, 41.9, 34.2, 34.1, 33.9, 33.7, 27.7, 27.5, 20.2, 20.1, 13.6; IR (KBr) ν: 3736, 3613, 3306, 3036, 2954, 2920, 2865, 1957, 1705, 1650, 1611, 1478, 1363, 1275, 1236, 1183, 1098, 1034, 996, 962, 919, 853, 809, 699, 647 cm⁻¹; MS (m/z): HRMS (ESI) calcd for C₃₉H₃₆N₃NaO₃ ([M + Na]⁺): 631.2680. Found: 631.2673.

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grant No. 21172189, 21572196) and the Priority Academic Program Development of Jiangsu Higher Education Institutions. We also thank the Analysis and Test Center of Yangzhou University providing instruments for analysis.

References

1. (a) J. V. Greenhill, Chem. Soc. Rev., 1977, 6, 277–294; (b) P. Lue and J. V. Greenhill, Adv. Heterocycl. Chem., 1997, 67, 215; (c) B. Stanovnik and J. Svete, Chem. Rev., 2004, 104, 2433–2480.
2. (a) R. F. Abdulla and R. S. Brinkmeyer, Tetrahedron, 1979, 35, 1675–1735; (b) A.-Z. Elassar and A. A. El-Khair, Tetrahedron, 2003, 59, 8463–8480.
3. (a) M. C. Bagley, J. W. Dale and J. Bower, Chem. Commun., 2002, 1682; (b) A. Valla, B. Valla, D. Cartier, R. Le Guillou, R. Labia and P. Potier, Tetrahedron Lett., 2005, 46, 6671–6674; (c) A. R. Katritzky, A. E. Hayden, K. Kirichenko, P. Pelphrey and Y. Ji, J. Org. Chem., 2004, 69, 5108–5111; (d) S. Cunha, F. Damasceno and J. Ferrari, Tetrahedron Lett., 2007, 48, 5795; (e) S. Kikuchi, M. Iwai, H. Murayama and S. Fukuzaka, Tetrahedron Lett., 2008, 49, 114–116.
4. (a) R. K. Vohra, C. Bruneau and J. Renaud, Adv. Synth. Catal., 2006, 348, 2571–2574; (b) A. Kumar and R. A. Maurya, Tetrahedron, 2008, 64, 3477–3482; (c) J. Moreau, A. Duboc, C. Hubert, J.-P. Hurvois and J. L. Renaud, Tetrahedron Lett., 2007, 48, 8647–8650; (d) H. Sirijindalert, K. Hansuthirakul, P. Rashatasakhon, M. Sukwattanasinitt and A. Ajavakom, Tetrahedron, 2010, 66, 5161–5167.
5. (a) B. Rechsteiner, F. Texier-Boullet and J. Hamelin, Tetrahedron Lett., 1993, 34, 5071–5074; (b) C. J. Valduga, A. Squizani, H. S. Braibante and M. E. F. Braibante, Synthesis, 1998, 1019–1022; (c) A. Arcadi, G. Bianchi, S. Di Giuseppe and F. Marinelli, Green Chem., 2003, 64–67; (d) A. R. Khosropour, M. M. Khodaei and M. Kookhazadeh, Tetrahedron Lett., 2004, 45, 1725–1728.
6. (a) T. Glotova, M. Dvorko, I. Ushakov, N. Chipanina, O. Kazheva, A. Chekhlov, O. Dyachenko, N. Gusarova and B. Trofimov, Tetrahedron, 2009, 65, 9814–9818; (b) A. Ziyaei-Halimehjani and M. R. Saidi, Tetrahedron Lett., 2008, 49, 1244–1248; (c) X. Li, J. Y. Wang, W. Yu and L. M. Wu, Tetrahedron, 2009, 65, 1140–1146; (d) I. Yavari, M. J. Bayat, M. Sirouspour and S. Souri, Tetrahedron, 2010, 66, 7995–7999.
7. (a) X. Li, W. Tan, Y. X. Gong and F. Shi, J. Org. Chem., 2015, 80(3), 1841–1848; (b) T. Huber, D. Kaiser, J. Rickmeier and T. Magauer, J. Org. Chem., 2015, 80(4), 2281–2294; (c) J. J. Zhao, Y. C. Zhang, M. M. Xu, M. Tang and F. Shi, J. Org. Chem., 2015, 80, 10016–10024; (d) W. Tan, B. X. Du, X. Li, X. Zhu, F. Shi and S. J. Tu, J. Org. Chem., 2014, 79, 4635–4643.
8. (a) S. Maity, S. Pathak and A. Pramanik, Eur. J. Org. Chem., 2014, 4651–4662; (b) Z. Y. Gu, X. Wang, J. J. Cao, S. Y. Wang and S. J. Ji, Eur. J. Org. Chem., 2015, 4699–4709; (c) S. Pathak, D. Das, A. Kundu, S. Maity, N. Guchhait and A. Pramanik, RSC Adv., 2015, 5(22), 17308–17318; (d) M. Sivaraman and P. T. Perumal, RSC Adv., 2014, 4(94), 52060–52066; (e) X. M. Lu, Z. J. Cai, J. Li, S. Y. Wang and S. J. Ji, RSC Adv., 2015, 5(64), 51501–51507.
9. (a) L. Fu, X. Feng, J. J. Wang, Z. Xun, J. D. Hu, J. J. Zhang, Y. W. Zhao, Z. B. Huang and D. Q. Shi, ACS Comb. Sci., 2015, 17(1), 24–31; (b) A. Mondal and C. Mukhopadhyay, ACS Comb. Sci., 2015, 17(7), 404–408; (c) H. X. Zou, A. S. Limpert, J. W. Zou, A. Dembo, P. S. Lee, D. Grant, R. Ardecky, A. B. Pinkerton, G. K. Magnuson and M. Goldman, ACS Chem. Neurosci., 2015, 6(3), 464–475.
10. (a) F. J. Zhao, M. Y. Sun, Y. J. Dang, X. Y. Meng, B. Jiang, W. J. Hao and S. J. Tu, Tetrahedron, 2014, 70(51), 9628–9634; (b) J. J. Zhang, X. Feng, X. C. Liu, Z. B. Huang and D. Q. Shi, Mol. Diversity, 2014, 18(4), 727–736; (c) A. Kundu and A. Pramanik, Mol. Diversity, 2015, 19(3), 459–471.
11. (a) J. Huang, Y. J. Liang, Y. Pan, Y. Yang and D. W. Dong, Org. Lett., 2007, 9, 75345–75348; (b) V. Sridharan and J. C. Menéndez, Org. Lett., 2008, 10, 4303–4306; (c) B. Jiang, Q. Y. Li, H. Zhang, S. J. Tu, S. Pindi and G. G. Li, Org. Lett., 2012, 14, 700–703; (d) H. Y. Wang, L. L. Li, W. Lin, P. Xu, Z. B. Huang and D. Q. Shi, Org. Lett., 2012, 14, 4598–4601.
12. (a) H. Mohrle and P. Arz, Arch. Pharm., 1986, 319(4), 303–310; (b) R. A. Kumar, C. K. Kokate, M. S. Rao and T. V. P. Rao, Org. Prep. Proced. Int., 1989, 21(3), 380–383; (c) H. A. Fattah, Orient. J. Chem., 2013, 29(2), 405–417; (d) E. Shaban, Md. I. Hossain, M. Y. Wu, Y. Takemasa, S. Nagae, W. Peng, H. Kawafuchi and T. Inokuchi, Heterocycles, 2014, 89(1), 171–182.
13. (a) N. L. Racheva, Z. G. Aliev and A. N. Maslivets, Russ. J. Org. Chem., 2008, 44(6), 836–839; (b) N. L. Racheva, Z. G. Aliev and A. N. Maslivets, Russ. J. Org. Chem., 2008, 44(6), 937–938; (c) E. S. Denislamova, Z. G. Aliev and A. N. Maslivets, Russ. J. Org. Chem., 2014, 50(7), 1012–1016.
14. (a) J. Sun, Y. Sun, H. Gao and C. G. Yan, Eur. J. Org. Chem., 2011, 6952–6956; (b) J. Sun, Y. Sun, H. Gao and C. G. Yan, Eur. J. Org. Chem., 2012, 1976–1983; (c) J. Sun, Y. Sun, H. Gong, Y. J. Xie and C. G. Yan, Org. Lett., 2012, 14, 5172–5175; (d) J. Sun, Y. J. Xie and C. G. Yan, J. Org. Chem., 2013, 78, 8354–8365; (e) H. Gao, J. Sun and C. G. Yan, J. Org. Chem., 2014, 79, 4131–4136; (f) J. Zhang, H. Gao, J. Sun and C. G. Yan, Eur. J. Org. Chem., 2014, 5598–5602.
15. (a) H. Gao, J. Sun and C. G. Yan, Synthesis, 2014, 46, 489–495; (b) F. Yang, L. J. Zhang and C. G. Yan, RSC Adv., 2014, 4, 64466–64475; (c) Y. J. Xie, J. Sun and C. G. Yan, RSC Adv., 2014, 4, 44537–44546; (d) L. J. Lu and C. G. Yan, Tetrahedron, 2014, 70, 9587–9591; (e) H. Gong, J. Sun and C. G. Yan, Tetrahedron, 2014, 70, 6641–6650; (f) G. L. Shen, J. Sun and C. G. Yan, RSC Adv., 2015, 5, 4475–4483.
16. (a) M. Y. Li, H. W. Xu, W. Fan, X. Wang, B. Jiang, S. L. Wang and S. J. Tu, Tetrahedron, 2014, 70, 1004–1010; (b) S. A. S. Ghozlan, M. F. Mohamed, A. G. Ahmed, S. A. Shouman, Y. M. Attia and I. A. Abdelhamid, Arch. Pharm. Chem. Life Sci., 2015, 348, 113–124.
17. (a) S. A. Babu, Synlett, 2002, 531; (b) W. P. Yen, P. L. Liu, N. Uramaru, H. Y. Lin and F. F. Wong, Tetrahedron, 2015, 71, 8798–8803; (c) Y. M. Tian, L. M. Tian, X. He, C. J. Li, X. S. Jia and J. Li, Org. Lett., 2015, 17(19), 4874–4877.
18. (a) S. Rehn and J. Bergman, Tetrahedron, 2005, 61, 3115–3123; (b) G. Shanthi and P. T. Perumal, Tetrahedron Lett., 2009, 50, 3959–3962; (c) Y. Han, Y. Sun, J. Sun and C. G. Yan, Tetrahedron, 2012, 68, 8256–8260; (d) L. L. Zhang, J. Sun and C. G. Yan, Tetrahedron, 2013, 69, 5451–5459; (e) D. Zhu, J. Sun and C. G. Yan, RSC Adv., 2014, 4, 62817–62826.

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Footnote

† Electronic supplementary information (ESI) available: ¹H and ¹³C NMR spectra for all new compounds are available. CCDC 1449888–1449891. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra08811b

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