Unimolecular tetrakis-piperidine-4-ol: an efficient ligand for copper and amine free Sonogashira coupling

Abstract

A unimolecular tetrakis-piperidine-4-ol has been developed as an efficient ligand in combination with Pd/C for copper and amine free Sonogashira coupling. Various aryl and heteroaryl iodides were successfully coupled with aliphatic and aromatic alkynes to give internal alkynes in good to excellent yields.

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Introduction

Transition metal-catalyzed cross coupling reactions to access C–C bond formation has revolutionized synthetic organic chemistry today. Among these reactions, Pd catalyzed C_(sp²)–C_(sp) coupling between vinyl halides/triflates and terminal alkynes (Sonogashira coupling reaction) has proven to be most effective for its simplicity and high tolerance toward various functional groups.¹ The internal alkyne moieties are sought after as important precursors in diverse areas of chemistry such as sensors,² non-linear optical materials/molecular electronics,³ dendrimers/polymers,⁴ natural products^5–9 and heterocycles synthesis.¹⁰ The Sonogashira coupling has been the key step in the synthesis of many natural products having potential medicinal activities such as COPD biomarker desmosine 1a,⁶ anti-HIV agents like (−)-isatisine A 1b,⁷ (+)-lithospermic acid 1c ⁸ and anticancer agent (−)-quinocarcin 1d ⁹ as examples (Fig. 1).

Fig. 1 Examples of internal alkyne intermediates synthesized via Sonogashira coupling for natural product synthesis.

In 1975, Heck¹¹ and Cassar¹² independently reported Pd-catalyzed coupling between C_(sp²) halide and terminal alkynes while Sonogashira and Hagihara¹³ demonstrated that Cu(I) iodide as a co-catalyst drastically improves the rate of alkynylation. However, the demerit of the Cu co-catalyzed Sonogashira coupling is the formation of by-product from oxidative coupling of alkynes via the Hay/Glaser reaction.¹⁴ As a result, the efficiency of reaction decreases coupled with wastage of terminal alkynes often prepared by multistep methods. To avoid this by-product, a variety of impressive modifications has been reported, such as use of a variety of ligands,¹⁵ solvents,¹⁶ phase transfer catalysts,¹⁷ biphasic versions,¹⁸ microwave media,¹⁹ polymer/solid supported Pd-catalyst.²⁰ Among these, the use of ligands is found to be economical and effective if in catalytic quantities. Ligand has the control over the binding to the metal during catalytic cycle and hence affects the reactivity of coupling reactions. The chelation of ligand with metal depends on three major properties: (a) electron donating ability, (b) steric properties and (c) bite angle; which have significant impact on the coupling reaction.²¹ The use of an appropriate ligand is therefore of paramount importance. In earlier days sterically bulky and electron-rich phosphine ligands were used. However these ligands are toxic, expensive, difficult to synthesize, easily decompose at higher temperatures, moisture sensitive and difficult to handle. To overcome the drawback associated with phosphine ligands, many developed N-based ligands as they are inexpensive, water soluble, have low toxicity and show high catalytic activity of Pd-complexes for the coupling reaction. The stability of Pd–N system and ‘non-leaching’ nature offer better alternatives. Palladium catalysts derived from bidentate N,N- or N,O-ligands such as DABCO,^15d,e BINAM,^15f phenanthroline,^15gN,N-dimethyl glycine,^15h 8-hydroxy quinoline¹⁵ⁱ have been tested as possible alternatives to phosphines in Sonogashira coupling. Bidentate ligands enhance the reductive elimination step in catalytic cycle by stabilizing a tetrahedral geometry, thereby enhancing the overall rate of the reaction.²²

Recently, we have reported the synthesis of unimolecular 4-hydroxy piperidines 2a–e (Fig. 2) via the cascade aza-Cope/aza-Prins cyclization from homoallylamines.²³ These conveniently obtained ligands showed excellent catalytic activity in the Ullmann and Suzuki coupling.²⁴ This promoted us to explore them for the C_(sp²)–C_(sp) coupling reaction (Sonogashira). We present our results in this paper.

Fig. 2 Ligands 2a–e prepared via the cascade aza-Cope/aza-Prins cyclization.²³

Results and discussion

The Sonogashira reaction was optimized using the model substrate iodobenzene 3 (1.0 mmol), phenylacetylene 4 (1.5 mmol, 1.5 equiv.) and Pd source as shown in Table 1. We tested the ligands 2a–e (1.0 mol%), using 10% Pd/C (1.0 mol%) in EtOH as solvent at 80 °C (Table 1, entries 1–5). Among them, the ligand 2e gave the best results (entry 5). Considering the common solvents used in Sonogashira coupling we checked DMA, CH₃CN, DMSO, DMF, NMP, 1,4-dioxane and H₂O at temperatures 80–120 °C (entries 6–12). We found EtOH was better (entry 5) giving 5g in 98% yield. We further examined various Pd-catalyst commonly used in this reaction (entries 13–18) and found Pd(PPh₃)₄ catalyzes the reaction similar to Pd/C (entry 5 vs. 18). Considering cost factor and ease of handling, we choose Pd/C for further optimization. Inspection of various inorganic and organic base additives (entries 19–27) indicated K₂CO₃ to be better (entry 5 vs. entries 19–27). Varying the ligand concentration 0.5 mol% (entry 28) or Pd/C to 0.5 mol% (entry 29) resulted in lower yields of 5g. The reaction without the ligand was very sluggish (18 h) and gave only 46% of 5g (entry 30). Thus, the use of Pd/C (1.0 mol%). Ligand 2e (1.0 mol%), K₂CO₃ (1.5 equiv.) in EtOH at 80 °C were chosen as optimum conditions.

Table 1 Optimization of Sonogashira coupling between iodobenzene 3 and phenylacetylene 4^a

Sr. no.	Catalyst (x mol%)	Ligand (y mol%)	Base (1.5 equiv.)	Solvent	Temp °C	t/h	Yield^b (%) 5g
a Reaction condition: iodobenzene 3 (1 mmol), phenylacetylene 4 (1.5 mmol), Pd/C (10% wt, 0.5–1.0 mol%), ligand (0.5–1.0 mol%), base (1.5 mmol), solvent (0.5 mL); reactions were carried out in pressure tube. b Isolated yield. c Without ligand.
1	Pd/C (1)	2a (1)	K2CO3	EtOH	80	10	68
2	Pd/C (1)	2b (1)	K2CO3	EtOH	80	12	68
3	Pd/C (1)	2c (1)	K2CO3	EtOH	80	10	72
4	Pd/C (1)	2d (1)	K2CO3	EtOH	80	12	85
5	Pd/C (1)	2e (1)	K2CO3	EtOH	80	4	98
6	Pd/C (1)	2e (1)	K2CO3	DMA	120	9	90
7	Pd/C (1)	2e (1)	K2CO3	CH3CN	110	12	86
8	Pd/C (1)	2e (1)	K2CO3	DMSO	120	5	75
9	Pd/C (1)	2e (1)	K2CO3	DMF	110	24	43
10	Pd/C (1)	2e (1)	K2CO3	NMP	100	20	30
11	Pd/C (1)	2e (1)	K2CO3	1,4-Dioxane	80	48	27
12	Pd/C (1)	2e (1)	K2CO3	H2O	80	48	20
13	Pd(OAc)2 (1)	2e (1)	K2CO3	EtOH	80	4	73
14	Pd(TFA)2 (1)	2e (1)	K2CO3	EtOH	80	4	89
15	Pd(dba)2 (1)	2e (1)	K2CO3	EtOH	80	4	84
16	PdCl2 (1)	2e (1)	K2CO3	EtOH	80	4	71
17	π-(Allyl PdCl2) (1)	2e (1)	K2CO3	EtOH	80	28	34
18	Pd(PPh3)4 (1)	2e (1)	K2CO3	EtOH	80	4	96
19	Pd/C (1)	2e (1)	K3PO4	EtOH	80	12	93
20	Pd/C (1)	2e (1)	NaOH	EtOH	80	40	95
21	Pd/C (1)	2e (1)	Pyridine	EtOH	80	20	28
22	Pd/C (1)	2e (1)	Et3N	EtOH	80	20	49
23	Pd/C (1)	2e (1)	Cs2CO3	EtOH	80	48	21
24	Pd/C (1)	2e (1)	Na2CO3	EtOH	80	20	26
25	Pd/C (1)	2e (1)	DIEA	EtOH	80	72	49
26	Pd/C (1)	2e (1)	Piperidine	EtOH	80	48	55
27	Pd/C (1)	2e (1)	Pyrrolidine	EtOH	80	48	78
28	Pd/C (1)	2e (0.5)	K2CO3	EtOH	80	4	68
29	Pd/C (0.5)	2e (1)	K2CO3	EtOH	80	12	68
30	Pd/C (1)	—	K2CO3	EtOH	80	18	46^c

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The scope and limitation of this method was examined for coupling of iodobenzene 3 with a variety of terminal alkynes 4 with aliphatic or aryl groups (Scheme 1). Alkynes such as 1-heptyne, propargyl alcohols and 3-butyne-1-ol with free or protected OH group delivered corresponding internal alkynes 5a–5f in 69–97% yields. Aryl and heteroaryl alkynes delivered the coupled products 5g–5j in excellent yields of 91–96%. We next investigated substituted iodobenzenes with electron donating and withdrawing groups in reactions with a variety of terminal alkynes (both aliphatic and aryl) to provide the coupled products 5k–w in good to excellent yields. The reaction did not show any general trend of aryl substituents dependence based on electronic factors. Sterically demanding ortho-phenyl, Me, CF₃ and NH₂ substituted iodobenzenes also reacted well to give the coupled products 5x–ae in good to quantitative yields with alkynes both aliphatic and aryl. The meta-OMe substituted iodobenzene delivered the coupled product 5af in 78% yield. Surprisingly, the reaction of iodobenzene with TMS-acetylene and acetyl protected homopropargyl alcohol did not yield the coupled products 5ag ²⁵ and 5ah respectively, probably due to their sensitivity. Also the reaction of arylbromides^15j,19b produced the coupled products in low to moderate yields, 5k (22%), 5t (31%) and 5x (24%). The corresponding reactions of chlorobenzene with phenylacetylene 4 did not yield the coupled products under the present protocol that is similar to known literature reports.^19b

Scheme 1 Sonogashira coupling of different iodo/bromobenzenes with a variety of alkynes. Reaction conditions: iodo/bromobenzene 3 (1.0 mmol), alkyne 4 (1.5 equiv.), K₂CO₃ (1.5 equiv.), EtOH (0.5 mL); reactions carried out in pressure tube.

Besides aromatic systems, we also examined the behaviour of heteroaromatic halides in Sonogashira reaction and found that these are also employable (Scheme 2). 3-Iodo pyridine 6a reacted well with terminal alkynes 4 having various alkyl or aryl groups to give the corresponding products 7a–7e in 84–94% yields. 2-Bromopyridine 6b reacted with phenylacetylene to furnish 7f in 66% yield after 24 h reaction.

Scheme 2 Sonogashira coupling of alkynes with 3-iodo and 2-bromopyridine. Reaction conditions: 6 (1.0 mmol), alkyne 4 (1.5 equiv.), K₂CO₃ (1.5 equiv.), EtOH (0.5 mL); reactions carried out in pressure.

We also considered recovery and reuse of Pd/C catalyst as shown in Scheme 3. Using the optimum conditions of Table 1, entry 5, we studied the activity of the recycled catalyst in the coupling of iodobenzene and phenylacetylene. We found that the Pd/C catalyst can be reused after filtration (Whatman no. 41 paper) and subsequent treatments such as washing with water, MeOH and drying. However, the activity of the recycled catalyst decreased after each run, though prolonged reaction time did result in full conversion in every repeated run (4, 6, 10 and 24 h, respectively). The addition of ligand and K₂CO₃ to the reused catalysts was necessary in every repeated run.

Scheme 3 Recycling of Pd/C over four runs.

Conclusions

In conclusion, we have successfully achieved the Sonogashira reaction of aryl or heteroaryliodo/bromo compounds with terminal alkynes without Cu co-catalyst and amine free in presence of 1 mol% Pd on charcoal and 1 mol% of the ligand 2e (40 examples). We have established that the optimum choice of the solvent, base and catalyst are crucial for the completion of the reactions. Our methodology provides efficient way to couple iodo/bromobenzene with a wide variety of aliphatic and arylterminal acetylenes. Besides this, the reaction conditions highlight the use of most readily available and easy to handle Pd/C catalyst providing also convenient and easy catalyst separation. The Pd/C catalyst can be recycled by a simple filtration and washing procedure and shows good activity even after four runs.

Experimental section

Flasks were oven or flame dried and cooled in desiccator. Solvents and reagents were purified by standard methods. Thin-layer chromatography was performed on EM 250 Kieselgel 60 F254 silica gel plates. The spots were visualized by staining with KMnO₄ or under UV lamp. ¹H and ¹³C NMR were recorded with a Bruker, AVANCE III 500 or 400 spectrometer and the chemical shifts are based on TMS peak at δ = 0.00 pm for proton NMR and CDCl₃ peak at δ = 77.00 ppm (t) in carbon NMR. IR spectra were obtained on Perkin Elmer Spectrum One FT-IR spectrometer and samples were prepared by evaporation from CHCl₃ on CsBr plates. High-resolution mass spectra (HRMS) were obtained using positive electrospray ionization by TOF method.

General procedure for the synthesis of internal alkynes 5a–ah and 7a–7f

To a solution of aryliodide or bromide 3 or 6 (1.0 mmol) in EtOH (0.5 mL) were added sequentially terminal alkyne 4 (1.5 mmol, 1.5 equiv.), K₂CO₃ (207.3 mg, 1.5 mmol, 1.5 equiv.), 10% Pd/C (1.1 mg, 0.01 mmol, 1 mol%) and ligand 2e (5.31 mg, 0.01 mmol, 1 mol%). The reaction mixture was refluxed at 80 °C for 4–24 h till the consumption of the arylhalide. Then the mixture was cooled to room temperature. After the removal of the solvent in vacuum, the residue was purified by silica gel column chromatography with petroleum ether–EtOAc (9 : 1 to 4 : 1) as eluent to give corresponding internal alkynes in good to excellent yields.

Hept-1-ynylbenzene (5a). Colorless oil; yield 132.6 mg (77%); IR (CHCl₃): ν = 3020, 2956, 2932, 2872, 1492, 1466, 1379, 1030, 701, 669 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.40–7.38 (m, 2H), 7.30–7.25 (m, 3H), 2.39 (t, J = 7.1 Hz, 2H), 1.64–1.59 (m, 2H), 1.47–1.39 (m, 2H), 1.38–1.33 (m, 2H), 0.92 (t, J = 7.3 Hz, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 131.5, 128.2, 127.4, 124.1, 90.5, 80.5, 31.1, 28.5, 22.2, 19.4, 14.0 ppm; HRMS (ESI-TOF) m/z calcd for C₁₃H₁₆Na [M + Na]⁺ 195.1144, found 195.1142.

3-Phenylprop-2-yn-1-ol (5b). Yellow oil; yield 120.3 mg (91%); IR (CHCl₃): ν = 3397, 2928, 2854, 1406, 1285, 1045, 959, 822 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.45–7.42 (m, 2H), 7.33–7.30 (m, 3H), 4.50 (s, 2H), 1.59 (br. s, 1H, OH) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 131.7, 128.5, 128.3, 122.5, 87.1, 85.7, 51.0 ppm; HRMS (ESI-TOF): m/z calcd for C₉H₈ONa [M + Na]⁺ 155.0467, found 155.0465.

4-Phenylbut-3-yn-1-ol (5c). Pale yellow oil; yield 141.8 mg (97%); IR (CHCl₃): ν = 3394, 2918, 1599, 1490, 1442, 1332, 1278, 1177, 1047, 915, 846, 692 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.43–7.40 (m, 2H), 7.31–7.28 (m, 3H), 3.78 (t, J = 6.3 Hz, 2H), 2.69 (t, J = 6.3 Hz, 2H), 2.02 (br. s, 1H, OH) ppm; ¹³C NMR (100 MHz, CDCl₃): δ = 131.6, 128.2, 127.9, 123.3, 86.3, 82.4, 61.1, 23.8 ppm; HRMS (ESI-TOF): m/z calcd for C₁₀H₁₁O [M + H]⁺ 147.0810, found 147.0804.

2-Methyl-4-phenylbut-3-yn-2-ol (5d). Brown solid; yield 110.5 mg (69%), mp 44–46 °C, (lit.²⁶ mp 51 °C); IR (CHCl₃): ν = 3382, 2923, 2234, 1599, 1572, 1490, 1442, 1333, 1279, 1178, 1047, 915, 846, 692, 667 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.43–7.40 (m, 2H), 7.31–7.28 (m, 3H), 1.75 (br. s, 1H, OH), 1.62 (s, 6H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 131.6, 128.2, 122.7, 93.7, 82.1, 65.6, 31.5 ppm; HRMS (ESI-TOF): m/z calcd for C₁₁H₁₂ONa [M + Na]⁺ 183.0786, found 183.0779.

tert-Butyldimethyl (3-phenylprop-2-ynyloxy)silane (5e). Colorless oil; yield 184.8 mg (75%); IR (CHCl₃): ν = 3398, 2929, 2857, 1488, 1462, 1449, 1408, 1390, 1256, 1044, 838, 774, 701, 670 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.44–7.41 (m, 2H), 7.31–7.29 (m, 3H), 4.54 (s, 2H), 0.94 (s, 9H), 0.17 (s, 6H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 131.6, 128.2, 123.0, 87.9, 84.8, 52.3, 25.9, 18.3, −5.0 ppm; HRMS (ESI-TOF): m/z calcd for C₁₅H₂₂OSiK [M + K]⁺ 285.1071, found 285.1071.

tert-Butyldimethyl(4-phenylbut-3-ynyloxy)silane (5f). Pale yellow oil; yield 218.8 mg (84%); IR (CHCl₃): ν = 2954, 2929, 2857, 1599, 1490, 1471, 1387, 1256, 1107, 1057, 914, 838, 777, 691 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.39–7.36 (m, 2H), 7.27–7.24 (m, 3H), 3.81 (t, J = 7.1 Hz, 2H), 2.62 (t, J = 7.1 Hz, 2H), 0.90 (s, 9H), 0.09 (s, 6H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 131.6, 128.2, 127.6, 123.8, 87.2, 81.5, 62.0, 25.9, 23.8, 18.4, −5.3 ppm; HRMS (ESI-TOF): m/z calcd for C₁₆H₂₄OSiNa [M + Na]⁺ 283.1489, found 283.1475.

1,2-Diphenylethyne (5g). Colorless solid; yield 171.1 mg (96%), mp 44–46 °C (lit.²⁷ mp 57–61 °C); IR (CHCl₃): ν = 3059, 2922, 1602, 1498, 1443, 1385, 1027, 916, 690, 666 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.56–7.51 (m, 4H), 7.38–7.31 (m, 6H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ = 131.6, 128.3, 128.2, 123.2, 89.3 ppm; HRMS (ESI-TOF): m/z calcd for C₁₄H₁₁ [M + H]⁺ 179.0855, found 179.0851.

1-(Phenylethynyl)naphthalene (5h). Pale yellow oil; yield 210.0 mg (92%); IR (CHCl₃): ν = 3057, 2955, 2928, 2857, 1598, 1586, 1576, 1506, 1489, 1442, 1397, 1333, 1305, 1252, 1160, 1146, 1069, 1024, 1013, 968, 913, 862, 798, 773, 689 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 8.46 (d, J = 8.3 Hz, 1H), 7.87 (t, J = 8.9 Hz, 2H), 7.79 (dd, J = 7.1, 0.9 Hz, 1H), 7.67 (dd, J = 7.8, 1.7 Hz, 2H), 7.65–7.59 (m, 1H), 7.57–7.49 (m, 1H), 7.47–7.41 (m, 1H), 7.41–7.36 (m, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ = 133.3, 133.2, 131.7, 130.4, 128.8, 128.4, 128.37, 128.3, 126.8, 126.4, 126.2, 125.3, 123.4, 120.9, 94.3, 87.5 ppm; HRMS (ESI-TOF): m/z calcd for C₁₈H₁₃ [M + H]⁺ 229.1017, found 229.1019.

2-Butyl-5-(phenylethynyl)thiophene (5i). Dark yellow oil; yield 230.7 mg (96%); IR (CHCl₃): ν = 3079, 3018, 2957, 2930, 2871, 2858, 2204, 1598, 1537, 1493, 1463, 1442, 1378, 1245, 1198, 1113, 1069, 1020, 912, 802, 689, 669 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.51–7.47 (m, 2H), 7.36–7.31 (m, 3H), 7.10 (d, J = 3.6 Hz, 1H), 6.68 (d, J = 3.6 Hz, 1H), 2.81 (t, J = 7.5 Hz, 2H), 1.69–1.63 (m, 2H), 1.43–1.37 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ = 148.3, 131.9, 131.3, 128.3, 128.1, 124.2, 123.2, 120.5, 92.2, 83.1, 33.6, 29.9, 22.1, 13.8 ppm; HRMS (ESI-TOF): m/z calcd for C₁₆H₁₇S [M + H]⁺ 241.1045, found 241.1048.

2-Butyl-5-(phenylethynyl)furan (5j). Dark yellow oil; yield 204.1 mg (91%); IR (CHCl₃): ν = 3017, 2959, 2932, 2873, 2209, 1604, 1538, 1485, 1466, 1380, 1303, 1151, 1100, 1017, 968, 912, 690, 668, 601 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.52–7.50 (m, 2H), 7.35–7.32 (m, 3H), 6.57 (d, J = 3.3 Hz, 1H), 6.02–6.00 (m, 1H), 2.65 (t, J = 7.6 Hz, 2H), 1.68–1.62 (m, 2H), 1.42–1.36 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 158.3, 135.2, 131.3, 128.4, 128.3, 122.6, 116.3, 106.4, 92.9, 80.0, 30.0, 28.0, 22.2, 13.8 ppm; HRMS (ESI-TOF): m/z calcd for C₁₆H₁₆OK [M + K]⁺ 263.0833, found 263.0840.

1-(Hept-1-ynyl)-4-methoxybenzene (5k). Colorless oil; yield 153.7 mg (76%); IR (CHCl₃): ν = 2956, 2932, 2860, 1607, 1572, 1510, 1464, 1442, 1378, 1289, 1247, 1173, 1106, 1036, 832, 662 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.33 (d, J = 8.9 Hz, 2H), 6.81 (d, J = 8.9 Hz, 2H), 3.79 (s, 3H), 2.38 (t, J = 7.1 Hz, 2H), 1.64–1.52 (m, 2H), 1.46–1.32 (m, 4H), 0.72 (t, J = 7.2 Hz, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 159.0, 132.8, 116.3, 113.8, 88.8, 80.2, 55.2, 31.1, 28.6, 22.2, 19.4, 14.0 ppm; HRMS (ESI-TOF): m/z calcd for C₁₄H₁₉O [M + H]⁺ 203.1430, found 203.1426.

4-(4-Methoxyphenyl)but-3-yn-1-ol (5l). Colorless oil; yield 119.8 mg (68%); IR (CHCl₃): ν = 3245, 2926, 2855, 1512, 1414, 1290, 1283, 1250, 1181, 1107, 1046, 1032, 912, 838, 768, 666 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.35 (d, J = 8.8 Hz, 2H), 6.82 (d, J = 8.8 Hz, 2H), 3.81–3.79 (m, 5H), 2.68 (t, J = 6.2 Hz, 2H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 159.3, 133.0, 115.4, 113.9, 84.7, 82.4, 61.3, 55.3, 23.9 ppm; HRMS (ESI-TOF): m/z calcd for C₁₁H₁₃O₂ [M + H]⁺ 177.0910, found 177.0907.

4-(4-Methoxyphenyl)-2-methylbut-3-yn-2-ol (5m). Yellow solid; yield 146.5 mg (77%); mp = 50–52 °C, (lit.²⁶ mp = 56 °C); IR (CHCl₃): ν = 3411, 2981, 2932, 2840, 1606, 1511, 1463, 1376, 1251, 1171, 1032, 961, 908, 834, 670 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.35 (d, J = 8.9 Hz, 2H), 6.82 (d, J = 8.9 Hz, 2H), 3.80 (s, 3H), 1.61 (s, 6H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ = 159.5, 133.1, 114.8, 113.9, 92.4, 82.0, 65.7, 55.3, 31.6 ppm; HRMS (ESI-TOF): m/z calcd for C₁₂H₁₄O₂Na [M + Na]⁺ 213.0886, found 213.0887.

tert-Butyl-[4-(4-methoxyphenyl)but-3-ynyloxy]dimethylsilane (5n). Colorless oil; yield 287.6 mg (99%); IR (CHCl₃): ν = 3006, 2955, 2931, 2856, 1607, 1510, 1464, 1289, 1248, 1172, 1106, 1036, 916, 835, 669 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.33 (d, J = 8.8 Hz, 2H), 6.81 (d, J = 8.9 Hz, 2H), 3.83–3.78 (m, 5H), 2.61 (t, J = 7.1 Hz, 2H), 0.92 (s, 9H), 0.09 (s, 6H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ = 159.1, 132.9, 115.9, 113.8, 85.5, 81.3, 62.1, 55.2, 25.9, 23.8, 18.4, −5.2 ppm; HRMS (ESI-TOF): m/z calcd for C₁₇H₂₆O₂SiNa [M + Na]⁺ 313.1594, found 313.1592.

1-Methoxy-4-(phenylethynyl)benzene (5o). Colorless oil; yield 179.1 mg (86%); IR (CHCl₃): ν = 2959, 2936, 2840, 1606, 1511, 1455, 1440, 1387, 1289, 1249, 1181, 1108, 1070, 1030, 944, 917, 834, 813, 692, 667 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.52–7.47 (m, 4H), 7.36–7.31 (m, 3H), 6.88 (d, J = 8.6 Hz, 2H), 3.84 (s, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ = 159.6, 133.0, 131.4, 128.3, 127.9, 123.6, 115.4, 114.0, 89.3, 88.0, 55.3 ppm; HRMS (ESI-TOF): m/z calcd for C₁₅H₁₂KO [M + K]⁺ 247.0520, found 247.0515.

1-(4-Methoxyphenylethynyl)naphthalene (5p). Yellow oil; yield 206.7 mg (80%); IR (CHCl₃): ν = 3056, 3011, 2951, 2934, 2836, 2210, 1605, 1585, 1575, 1510, 1464, 1440, 1396, 1302, 1287, 1250, 1173, 1148, 1106, 1070, 1035, 831, 799 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 8.44 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.74 (d, J = 7.1 Hz, 1H), 7.61–7.58 (m, 3H), 7.55–7.53 (m, 1H), 7.45 (t, J = 7.8 Hz, 1H), 6.93 (d, J = 8.7 Hz, 2H), 3.86 (s, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 159.7, 133.2, 133.1, 130.0, 128.4, 128.3, 126.6, 126.4, 126.3, 125.3, 121.2, 115.5, 114.1, 94.3, 86.2, 55.3 ppm; HRMS (ESI-TOF): m/z calcd for C₁₉H₁₅O [M + H]⁺ 259.1117, found 259.1120.

2-Butyl-5-(4-methoxyphenylethynyl)thiophene (5q). Brown oil; yield 202.8 mg (75%); IR (CHCl₃): ν = 2956, 2930, 2872, 1606, 1539, 1510, 1465, 1441, 1378, 1291, 1249, 1173, 1108, 1034, 832, 801, 667 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.43 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 3.6 Hz, 1H), 6.86 (d, J = 8.8 Hz, 2H), 6.66 (d, J = 3.6 Hz, 1H), 3.82 (s, 3H), 2.79 (t, J = 7.6 Hz, 2H), 1.69–1.61 (m, 2H), 1.44–1.33 (m, 2H), 0.93 (t, J = 7.3 Hz, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 159.6, 147.8, 132.8, 131.4, 124.1, 120.9, 115.3, 114.0, 92.2, 81.7, 55.3, 33.6, 29.9, 22.1, 13.8 ppm; HRMS (ESI-TOF): m/z calcd for C₁₇H₁₉OS [M + H]⁺ 271.1151, found 271.1154.

tert-Butyldimethyl(4-p-tolylbut-3-ynyloxy)silane (5r). Yellow oil; yield 178.4 mg (65%); IR (CHCl₃): ν = 3005, 2955, 2931, 2857, 1607, 1510, 1464, 1290, 1248, 1172, 1106, 1036, 916, 835, 776, 669 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.28 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 7.9 Hz, 2H), 3.81 (t, J = 7.1 Hz, 2H), 2.61 (t, J = 7.1 Hz, 2H), 2.33 (s, 3H), 0.91 (s, 9H), 0.09 (s, 6H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 137.6, 131.4, 128.9, 120.7, 86.3, 81.6, 62.0, 25.9, 23.8, 21.4, 18.4, −5.2 ppm; HRMS (ESI-TOF): m/z calcd for C₁₇H₂₆OSiNa [M + Na]⁺ 297.1645, found 297.1643.

1-Methyl-4-(phenylethynyl)benzene (5s). White solid; yield 157.6 mg (82%); mp 61–63 °C (lit.²⁸ mp 70 °C); IR (CHCl₃): ν = 3079, 3050, 2937, 1595, 1569, 1510, 1441, 1388, 1105, 1070, 1044, 968, 949, 916, 873, 818, 690 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.54–7.51 (m, 2H), 7.43 (d, J = 8.1 Hz, 2H), 7.37–7.31 (m, 3H), 7.16 (d, J = 7.8 Hz, 2H), 2.37 (s, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 138.4, 132.5, 131.5, 129.1, 128.3, 128.1, 123.5, 120.2, 89.5, 88.7, 21.5 ppm; HRMS (ESI-TOF): m/z calcd for C₁₅H₁₃ [M + H]⁺ 193.1017, found 193.1008.

1-(Hept-1-ynyl)-4-nitrobenzene (5t). Yellow oil; yield 195.5 mg (90%); IR (CHCl₃): ν = 2959, 2932, 2864, 1595, 1519, 1493, 1466, 1343, 1307, 1286, 1175, 1108, 1021, 854, 751, 689 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 8.14 (d, J = 8.6 Hz, 2H), 7.51 (d, J = 8.6 Hz, 2H), 2.43 (t, J = 7.1 Hz, 2H), 1.66–1.59 (m, 2H), 1.46–1.34 (m, 4H), 0.93 (t, J = 7.2 Hz, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 146.5, 132.2, 131.2, 123.5, 96.8, 79.3, 31.1, 28.1, 22.2, 19.5, 13.9 ppm; HRMS (ESI-TOF): m/z calcd for C₁₃H₁₆NO₂ [M + H]⁺ 218.1176, found 218.1177.

4-(4-Nitrophenyl)but-3-yn-1-ol (5u). Yellow solid; yield 137.7 mg (72%); mp 72–74 °C (lit.²⁹ mp 76–78 °C); IR (CHCl₃): ν = 3389, 3108, 3020, 2939, 1594, 1517, 1493, 1344, 1308, 1286, 1261, 1175, 1107, 1045, 855, 751, 690 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 8.16 (d, J = 8.9 Hz, 2H), 7.55 (d, J = 8.9 Hz, 2H), 3.88–3.84 (m, 2H), 2.74 (t, J = 6.3 Hz, 2H), 1.81 (br. s, 1H, OH) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 146.9, 132.4, 130.4, 123.5, 92.6, 80.8, 60.9, 23.9 ppm; HRMS (ESI-TOF): m/z calcd for C₁₀H₁₀NO₃ [M + H]⁺ 192.0655, found 192.0651.

tert-Butyldimethyl[4-(4-nitrophenyl)but-3-ynyloxy]silane (5v). Yellow solid; yield 250.5 mg (82%); mp 48–51 °C; IR (CHCl₃): ν = 2949, 2929, 2888, 2859, 1595, 1519, 1493, 1472, 1346, 1310, 1286, 1256, 1110, 1020, 850, 839, 621 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 8.15 (d, J = 8.9 Hz, 2H), 7.52 (d, J = 8.9 Hz, 2H), 3.83 (t, J = 6.8 Hz, 2H), 2.67 (t, J = 6.8 Hz, 2H), 0.91 (s, 9H), 0.09 (s, 6H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 146.7, 132.3, 130.8, 123.5, 93.6, 80.1, 61.5, 25.8, 24.0, 18.3, −5.3 ppm; HRMS (ESI-TOF): m/z calcd for C₁₆H₂₄NO₃Si [M + H]⁺ 306.1520, found 306.1521.

1-Nitro-4-(phenylethynyl)benzene (5w). Yellow solid; yield 178.6 mg (80%); mp 108–110 °C (lit.³⁰ mp 119–120 °C); IR (CHCl₃): ν = 3103, 3081, 2930, 2849, 1594, 1538, 1510, 1442, 1353, 1308, 1287, 1175, 1108, 1094, 1071, 1020, 921, 856, 748, 689, 507 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 8.22 (d, J = 8.9 Hz, 2H), 7.67 (d, J = 8.9 Hz, 2H), 7.57–7.55 (m, 2H), 7.41–7.38 (m, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 147.0, 132.3, 131.8, 130.3, 129.3, 128.5, 123.6, 122.1, 94.7, 87.5 ppm; HRMS (ESI-TOF): m/z calcd for C₁₄H₁₀NO₂ [M + H]⁺ 224.0706, found 224.0706.

2-(Hept-1-ynyl)biphenyl (5x). Colorless oil; yield 208.6 mg (84%); IR (CHCl₃): ν = 3020, 2931, 2705, 1462, 1387, 1252, 1168, 1071, 1041, 1033, 1019, 904, 778, 701, 613 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.60–7.57 (m, 2H), 7.52–7.49 (m, 1H), 7.42–7.38 (m, 2H), 7.38–7.32 (m, 2H), 7.31–7.27 (m, 2H), 2.28 (t, J = 7.0 Hz, 2H), 1.48–1.44 (m, 2H), 1.29–1.24 (m, 4H), 0.87 (t, J = 7.1 Hz, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 143.6, 140.8, 132.9, 129.4, 129.3, 127.8, 127.7, 127.2, 126.9, 122.4, 93.5, 80.1, 30.9, 28.1, 22.2, 19.5, 14.0 ppm; HRMS (ESI-TOF): m/z calcd for C₁₉H₂₀OK [M + K]⁺ 287.1197, found 287.1199.

4-(Biphenyl-2-yl)but-3-yn-1-ol (5y). Pale yellow oil; yield 222.2 mg (quant.); IR (CHCl₃): ν = 3349, 3060, 3022, 2927, 1500, 1476, 1433, 1384, 1328, 1261, 1182, 1097, 1044, 950, 916, 845, 700, 668 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.57–7.51 (m, 3H), 7.46–7.42 (m, 2H), 7.39–7.35 (m, 3H), 7.30–7.28 (m, 1H), 3.62–3.56 (m, 2H), 2.55 (t, J = 6.0 Hz, 2H), 1.49 (br. s, 1H, OH) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 144.0, 140.9, 132.7, 129.3, 129.1, 128.1, 127.9, 127.5, 127.1, 121.7, 89.5, 82.3, 60.9, 24.0 ppm; HRMS (ESI-TOF): m/z calcd for C₁₆H₁₅O [M + H]⁺ 223.1117, found 223.1117.

4-(Biphenyl-2-yl)-2-methylbut-3-yn-2-ol (5z). Pale yellow oil; yield 167.8 mg (71%); IR (CHCl₃): ν = 3362, 2979, 2928, 2854, 1477, 1449, 1432, 1376, 1363, 1276, 1164, 961, 909, 700 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.57 (d, J = 7.2 Hz, 2H), 7.52 (d, J = 7.7 Hz, 1H), 7.43–7.34 (m, 5H), 7.31–7.27 (m, 1H), 1.6 (br. s, 1H, OH), 1.46 (s, 6H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 144.1, 140.5, 132.7, 129.3, 129.26, 128.5, 127.8, 127.4, 127.0, 121.0, 96.5, 82.0, 65.6, 31.0 ppm; HRMS (ESI-TOF): m/z calcd for C₁₇H₁₆ONa [M + Na]⁺ 259.1093, found 259.1090.

[4-(Biphenyl-2-yl)but-3-ynyloxy]tert-butyldimethylsilane (5aa). Pale yellow oil; yield 279.3 mg (83%); IR (CHCl₃): ν = 3012, 2954, 2929, 2857, 1473, 1434, 1388, 1361, 1256, 1104, 1057, 913, 837, 699, 668 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.58 (d, J = 7.8 Hz, 2H), 7.51 (d, J = 7.7 Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H), 7.36–7.28 (m, 4H), 3.67 (t, J = 7.4 Hz, 2H), 2.50 (t, J = 7.4 Hz, 2H), 0.90 (s, 9H), 0.05 (s, 6H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 143.7, 140.7, 133.0, 129.4, 129.3, 127.9, 127.8, 127.2, 126.9, 122.0, 89.9, 81.2, 61.8, 25.9, 23.9, 18.3, −5.3 ppm; HRMS (ESI-TOF): m/z calcd for C₂₂H₂₈OSiNa [M + Na]⁺ 359.1802, found 359.1801.

2-(Phenylethynyl)biphenyl (5ab). Colorless oil; yield 211.1 mg (83%); IR (CHCl₃): ν = 3058, 3022, 2928, 1598, 1491, 1473, 1449, 1433, 1385, 1310, 1261, 1180, 1160, 1103, 1070, 1048, 949, 914, 874, 736, 699, 690, 667 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.70–7.66 (m, 3H), 7.49–7.41 (m, 5H), 7.41–7.39 (m, 3H), 7.37–7.28 (m, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 143.9, 140.5, 132.8, 131.3, 129.5, 129.4, 128.5, 128.2, 128.1, 127.9, 127.4, 127.0, 123.4, 121.6, 92.2, 89.4 ppm; HRMS (ESI-TOF): m/z calcd for C₂₀H₁₅ [M + H]⁺ 255.1174, found 255.1162.

1-Methyl-2-(phenylethynyl)benzene (5ac). Colorless oil; yield 192.2 (quant.); IR (CHCl₃): ν = 3061, 3023, 2923, 2854, 1601, 1571, 1494, 1455, 1443, 1380, 1313, 1159, 1104, 1070, 943, 913, 715, 690 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.60–7.58 (m, 2H), 7.55 (d, J = 7.6 Hz, 1H), 7.42–7.37 (m, 3H), 7.28 (d, J = 4.0 Hz, 2H), 7.24–7.21 (m, 1H), 2.57 (s, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 140.2, 131.8, 131.5, 129.4, 128.3, 128.28, 128.2, 125.6, 123.5, 123.0, 93.3, 88.3, 20.7 ppm; HRMS (ESI-TOF): m/z calcd for C₁₅H₁₃ [M + H]⁺ 193.1017, found 193.1014.

1-(Phenylethynyl)-2-(trifluoromethyl)benzene (5ad). Colorless oil; yield 192.1 mg (78%); IR (CHCl₃): ν = 2927, 2857, 1605, 1497, 1451, 1321, 1313, 1262, 1173, 1135, 1111, 1057, 1033, 765, 691 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 7.70–7.66 (m, 2H), 7.58–7.55 (m, 2H), 7.54–7.50 (m, 1H), 7.44–7.38 (m, 1H), 7.38–7.36 (m, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 133.7, 131.7, 131.4, 128.8, 128.4, 127.9, 125.9 (J = 5.0 Hz), 124.7, 122.7, 122.5, 121.6, 94.9, 85.3 ppm; ¹⁹F NMR (400 MHz, CDCl₃): −62.4 ppm; HRMS (ESI-TOF) m/z calcd for C₁₅H₁₀F₃ [M + H]⁺ 247.0735, found 247.0742.

2-(Phenylethynyl)aniline (5ae). Pale yellow solid; yield 114 mg (59%); mp 82–84 °C, (lit.^15j mp 88–89 °C); IR (CHCl₃): ν = 3383, 2959, 2922, 2851, 1493, 1483, 1455, 1312, 1258, 1153, 691 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.56–7.52 (m, 2H), 7.39–7.37 (m, 1H), 7.37–7.31 (m, 3H), 7.17–7.12 (m, 1H), 6.80–6.74 (m, 2H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 146.9, 132.2, 131.5, 129.7, 128.3, 128.2, 123.2, 118.5, 114.8, 108.5, 94.8, 85.7 ppm; HRMS (ESI-TOF): m/z calcd for C₁₄H₁₁NNa [M + Na]⁺ 216.0784, found 216.0781.

1-Methoxy-3-(phenylethynyl)benzene (5af). Brown oil; yield 162.4 (78%); IR (CHCl₃): ν = 2926, 2854, 1604, 1583, 1495, 1465, 1323, 1283, 1235, 1184, 1159, 1122, 1046, 966, 931, 689 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 7.57–7.53 (m, 2H), 7.39–7.34 (m, 3H), 7.27 (t, J = 7.8 Hz, 1H), 7.17–7.14 (m, 1H), 7.09 (dd, J = 2.5, 1.5 Hz, 1H), 6.93–6.90 (m, 1H), 3.84 (s, 3H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ = 159.3, 131.6, 129.4, 128.3, 128.27, 124.2, 124.15, 123.2, 116.3, 114.9, 89.3, 89.2, 55.2 ppm; HRMS (ESI-TOF): m/z calcd for C₁₅H₁₃O [M + H]⁺ 209.0966, found 209.0965.

3-(Hept-1-ynyl)pyridine (7a). Dark yellow oil; yield 145.5 mg (84%); IR (CHCl₃): ν = 3016, 2955, 2937, 2871, 2859, 2800, 1508, 1456, 1440, 1329, 1200, 1188, 1105, 1023, 834, 805, 778, 730, 706, 670 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 8.62 (s, 1H), 8.51–8.46 (m, 1H), 7.67–7.64 (m, 1H), 7.21–7.19 (m, 1H), 2.41 (t, J = 7.2 Hz, 2H), 1.64–1.46 (m, 2H), 1.45–1.34 (m, 4H), 0.92 (t, J = 7.2 Hz, 3H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 152.3, 147.8, 138.4, 122.9, 121.2, 94.2, 77.3, 31.1, 28.2, 22.2, 19.4, 14.0 ppm; HRMS (ESI-TOF): m/z calcd for C₁₂H₁₆N [M + H]⁺ 174.1277, found 174.1277.

4-(Pyridin-3-yl)but-3-yn-1-ol (7b). Dark yellow oil; yield 138.3 mg (94%); IR (CHCl₃): ν = 3375, 2935, 2923, 2885, 1566, 1478, 1410, 1332, 1218, 1188, 1122, 1057, 1027, 925, 847, 808, 705, 635 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 8.62 (s, 1H), 8.47 (d, J = 4.8 Hz, 1H), 7.68–7.66 (m, 1H), 7.21 (dd, J = 7.8, 4.9 Hz, 1H), 3.83 (t, J = 6.3 Hz, 2H), 2.70 (t, J = 6.3 Hz, 2H), 2.0 (br. s, 1H, OH) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 152.2, 148.0, 138.7, 123.0, 120.7, 90.6, 78.8, 60.8, 23.8 ppm; HRMS (ESI-TOF): m/z calcd for C₉H₁₀NO [M + H]⁺ 148.0757, found 148.0758.

2-Methyl-4-(pyridin-3-yl)but-3-yn-2-ol (7c). Colorless solid; yield 138.6 mg (86%); mp 43–46 °C (lit.³¹ mp = 53 °C); IR (CHCl₃): ν = 3376, 2982, 2931, 2860, 1588, 1568, 1478, 1409, 1377, 1361, 1328, 1278, 1192, 1169, 1098, 1046, 1026, 966, 908, 808, 704, 633 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 8.72 (s, 1H), 8.50–8.45 (m, 1H), 7.69 (dd, J = 7.9, 1.3 Hz, 1H), 7.24–7.21 (m, 1H), 1.61 (s, 6H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 151.9, 148.0, 138.8, 123.1, 120.2, 98.1, 78.3, 65.0, 31.3 ppm; HRMS (ESI-TOF): m/z calcd for C₁₀H₁₂ON [M + H]⁺ 162.0919, found 162.0916.

3-[4-(tert-Butyldimethylsilyloxy)but-1-ynyl]pyridine (7d). Dark yellow oil; yield 240.5 mg (92%); IR (CHCl₃): ν = 2955, 2930, 2904, 2884, 2858, 1562, 1473, 1464, 1408, 1389, 1362, 1257, 1186, 1108, 1058, 1024, 917, 838, 806, 777, 706, 667 cm⁻¹; ¹H NMR (500 MHz, CDCl₃/TMS): δ = 8.62 (s, 1H), 8.49–8.46 (m, 1H), 7.66 (d, J = 7.9 Hz, 1H), 7.21 (dd, J = 7.8, 4.9 Hz, 1H), 3.82 (t, J = 6.9 Hz, 2H), 2.64 (t, J = 6.9 Hz, 2H), 0.91 (s, 9H), 0.09 (s, 6H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 152.3, 148.0, 138.5, 122.9, 120.9, 91.0, 78.3, 61.7, 25.9, 23.8, 18.3, −5.3 ppm; HRMS (ESI-TOF): m/z calcd for C₁₅H₂₄NOSi [M + H]⁺ 262.1622, found 262.1621.

3-(Phenylethynyl)pyridine (7e). Yellow crystalline solid; yield 166.7 mg (93%); mp 43–45 °C; IR (CHCl₃): ν = 3074, 2949, 2927, 2854, 1601, 1559, 1493, 1474, 1442, 1408, 1330, 1260, 1186, 1119, 1097, 1070, 1038, 952, 915, 805, 773, 705, 691 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 8.77–8.76 (m, 1H), 8.55 (dd, J = 4.9, 1.6 Hz, 1H), 7.82–7.79 (m, 1H), 7.57–7.53 (m, 2H), 7.39–7.35 (m, 3H), 7.30–7.27 (m, 1H) ppm; ¹³C NMR (100 MHz, CDCl₃): δ = 152.2, 148.5, 138.4, 131.7, 128.8, 128.4, 123.0, 122.5, 120.5, 92.6, 85.9 ppm; HRMS (ESI-TOF): m/z calcd for C₁₃H₁₀N [M + H]⁺ 180.0813, found 180.0807.

2-(Phenylethynyl)pyridine (7f). Brown oil; yield 118.3 mg (66%); IR (CHCl₃): ν = 2926, 2854, 1582, 1561, 1492, 1463, 1428, 1377, 1260, 1158, 1046, 913, 776, 690, 669 cm⁻¹; ¹H NMR (400 MHz, CDCl₃/TMS): δ = 8.63 (d, J = 4.4 Hz, 1H), 7.71 (td, J = 7.7, 1.7 Hz, 1H), 7.61 (dd, J = 6.5, 2.1 Hz, 2H), 7.55 (d, J = 7.8 Hz, 1H), 7.38–7.35 (m, 3H), 7.28–7.24 (m, 1H) ppm; ¹³C NMR (125 MHz, CDCl₃): δ = 149.7, 143.2, 136.5, 132.1, 129.1, 128.4, 127.2, 122.8, 122.2, 89.9, 88.2 ppm; HRMS (ESI-TOF): m/z calcd for C₁₃H₁₀N [M + H]⁺ 180.0808, found 180.0803.

Acknowledgements

We thank the Council of Scientific and Industrial Research (CSIR), New Delhi, Grant no. 02(0158)/13/EMR-II for financial support. P.H.P. thanks University Grants Commission (UGC) for a research fellowship.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Copies of ¹H and ¹³C NMR spectra for all the compounds. See DOI: 10.1039/c5ra07754k

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