Facile synthesis of heavily-substituted alkynylpyridines via a Sonogashira approach

Abstract

A facile and efficient synthetic route to densely substituted alkynylpyridines via a Sonogashira approach is reported. When treated with terminal alkynes in the presence of 5 mol% PdCl₂(PPh₃)₂, 5 mol% CuI and excess Et₃N in DMF at 65 °C, iodopyridines underwent Sonogashira coupling to afford alkynyl-substituted pyridines in good to excellent yields. The coupling reaction has been found to be general for a wide range of iodopyridines and terminal alkynes, and tolerated the presence of aliphatic, aromatic, heteroaromatic and ferrocenyl groups with electron-withdrawing and electron-donating substituents. This coupling approach could allow for the rapid construction of a library of functionalized alkynylpyridines of pharmacological interest.

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1. Introduction

Pyridines constitute one of the most important classes of heterocyclic compounds, and appear in many naturally occurring bioactive molecules and pharmaceutical compounds.¹ In fact, the pyridine moiety has found countless applications in catalysis, drug design, molecular recognition and natural product synthesis.² Moreover, pyridines are frequently employed as building blocks for pharmaceutical research since they are present in the structures of a variety of leading drugs, including HIV antiviral Atazanavir,³ hipnotic and sedative Eszopiclone,⁴ antineoplastic and anticancer Imatinib,⁵ cholesterol and triglyceride regulator Niacin,⁶ bone calcium regulator Risedronate,⁷ antihistaminic Desloratadine,⁸ antidiabetic Pioglitazone,⁹ and antiulcerants Esomeprazole,¹⁰ Pantoprazole,¹¹ Dexlansoprazole,¹² Lansoprazole,¹³ Omeprazole¹⁴ and Rapeprazole.¹⁵ Pyridines are found in structurally diverse natural products as well, like Diploclidine and Nakinadine A.¹⁶ Notably, most of pyridine-based alkaloid natural products are the derivatives of nicotinic acid (known also as vitamin B3 and Niacin).¹⁷ Pyridines are also employed in the preparation of conjugated polymers that are commonly used in light-emitting devices (LEDs).¹⁸ Pyridines are mainly synthesized by two methods; condensation of carbonyl compounds with amines,¹⁹ and cycloaddition of azadienes and nitriles with alkenes and alkynes.²⁰ In fact, over the years, various methods have been developed for the synthesis of pyridines,²¹ and new ones continue to appear since pyridines are critical intermediates for the syntheses of numerous drugs and natural products.²²

In particular, alkynylpyridines have attracted much attention due to their SMAC mimetic and PI3K inhibitory activities, and use in the treatment and/or prevention of diseases characterized by excessive or abnormal cell proliferation and associated conditions such as cancer.²³ Alkynylpyridines are very useful substrates in organic syntheses as well, since their triple bonds can easily undergo a range of reactions, including nucleophilic, electrophilic, radical and cycloaddition reactions, thus allowing their further functionalization and derivatization. Alkynylpyridines have been enormously utilized in the synthesis of azaindoles, furo[3,4-b]pyridines, indolizines, 1,6-naphthyridines, quinolines, 1,2,3-triazolo[4,5-f]quinolines, isoquinolines, N-metallacycles and supramolecular frameworks.²⁴ As a result, the synthesis of new, functionalized and densely substituted alkynylpyridines attracts increasing interest of researchers from both synthetic and biological points of view.

Recently, N-propargylic β-enaminones and β-enaminoesters have emerged as precious substrates for the synthesis of a variety of important heterocycles,²⁵ including pyridines²⁶ and dihydropyridines.²⁷ In this regard, we have recently described the synthesis of N-propargylic β-enaminones 3 from α,β-alkynic ketones 1 and their selective conversion into 5-iodopyridines 4 (Scheme 1).²⁸ Iodocyclization has been general for a variety of N-propargylic β-enaminones and tolerated the presence of aliphatic, aromatic and heteroaromatic groups with electron-withdrawing and electron-donating substituents.²⁸ It is noteworthy that iodine-containing pyridines are very useful building blocks for the synthesis of diverse natural products and pharmaceuticals as they can be easily elaborated to more complex structures by metal-catalyzed coupling reactions.²⁹ In this respect, we have recently shown that Suzuki–Miyaura reaction of 5-iodopyridines 4 with boronic acids has afforded a diverse range of densely substituted 5-arylpyridines 5 (Scheme 1).³⁰ In particular, the coupling of iodopyridines with terminal alkynes, classified as Sonogashira reaction,³¹ may offer a rapid entry to heavily-substituted alkynylpyridines that provide a platform for biological activity studies. From the structure–activity relationships, it has been concluded that the number of substituents, such as aryl group, attached to pyridine core is critical for their biological activities.³² For instance, the corresponding pyridines bearing more aryl groups have displayed stronger biological activity than those containing less aryl groups.³² Notably, an increase in the number of substituents via introduction of alkyne functionality into pyridine ring could result in beneficial biological properties. Alkyne functionality can also allow the conversion into other heterocycles for specific purposes. Our continued interest³³ in the synthesis of new ferrocenyl, carbocyclic and heterocyclic compounds as potential pharmaceuticals and scaffolds has prompted us to investigate the Sonogashira coupling reaction between iodopyridines and terminal alkynes. We herein report the full details of this study.

Scheme 1 Synthesis of iodopyridines from α,β-alkynic ketones and their further functionalization through Suzuki–Miyaura coupling reaction.

2. Results and discussion

The requisite 5-iodopyridines 4 were prepared from α,β-alkynic ketones 1 according to a recent report as shown in Scheme 1 (for identity of R groups and yields, see ESI‡).²⁸ We next investigated their Sonogashira reaction with terminal alkynes for the rapid access to 5-alkynylpyridines 7. In order to find optimal reaction conditions, we first examined the reaction between iodopyridine 4a and phenylacetylene (6a) under different conditions, as depicted in Table 1. Initially, the reaction was carried out overnight at room temperature in DCM, THF, CH₃CN, dioxane, DMF and DMSO by using 5 mol% PdCl₂(PPh₃)₂, 5 mol% CuI, excess Et₃N and 1.5 equiv. of phenylacetylene (6a), relative to iodopyridine 4a (Table 1, entries 1–6). In order to minimize homocoupling reaction, alkyne was added very slowly to the reaction medium and the reactions were run under argon atmosphere.³⁴ The overnight reactions in DCM, THF, CH₃CN and dioxane did not entirely reach the completion and produced alkynylpyridine 7a in 40–79% yields along with some recovered starting iodopyridine 4a (Table 1, entries 1–4). However, the reactions in DMF and DMSO went to completion and afforded alkynylpyridine 7a in 83 and 82% yields, respectively (Table 1, entries 5 and 6). Although the yields obtained in DMF and DMSO are very comparable, we chose DMF as the reaction solvent since it is more easily removed than DMSO. When the reaction in DMF was performed at 65 °C, the reaction went to completion in 1.5 h and afforded alkynylpyridine 7a in 91% yield (Table 1, entry 7). However, the same reaction at higher temperature such as 100 °C did not increase the yield of 7a; instead, 7a was obtained in relatively lower yield (76%) (Table 1, entry 8). Clearly, moderate temperature such as 65 °C provided the higher yield of 7a. Next we determined the effective number of equivalents of terminal alkyne in the reaction. When the reaction was performed in turn with one and two molar equivalents of phenylacetylene (6a), it produced alkynylpyridine 7a in 68 and 91% yields, respectively (Table 1, entries 9 and 10). Obviously, the lower number of equivalents (1.0 equiv.) of terminal alkyne decreased the yield of 7a while a higher number of equivalents (2.0 equiv.) did not improve the yield. Thus the reactions were carried out with 1.5 equiv. of terminal alkyne. We also tested the reaction in the absence and at a lower mol% of PdCl₂(PPh₃)₂ (Table 1, entries 11 and 12). In the absence of catalyst, no product formation was observed and the starting iodopyridine 4a was recovered with some decomposition (Table 1, entry 11). When the reaction was conducted with 2 mol% of the catalyst, alkynylpyridine 7a was isolated in relatively lower yield (78%) (Table 1, entry 12). Hence the reactions were carried out with 5 mol% of PdCl₂(PPh₃)₂. Finally, when the reaction was carried out in the absence of CuI, alkynylpyridine 7a was obtained in slightly lower yield (89%) (Table 1, entry 13). In summary, Sonogashira coupling reactions of iodopyridines were performed with 5 mol% PdCl₂(PPh₃)₂, 5 mol% CuI and 1.5 equiv. of terminal alkyne, with respect to starting iodopyridine, in DMF at 65 °C (i.e., with the conditions in entry 7 of Table 1). The results from a systematic study are shown in Table 2.

Table 1 Optimization studies for Sonogashira reaction of iodopyridine 4a with phenylacetylene (6a)^a

Entry	Alkyne (equiv.)	PdCl2(PPh3)2 (mol%)	CuI (mol%)	Solvent	Temp. (°C)	Time (h)	Yield (%)^b
a The optimization reactions were carried out on a 0.15 mmol scale of iodopyridine 4a by using 2.25 mL of Et3N under the indicated conditions.b Isolated yield.c The starting iodopyridine 4a was recovered in 45% yield as well.d The starting iodopyridine 4a was recovered in 13% yield as well.e The starting iodopyridine 4a was recovered in 10% yield as well.f The starting iodopyridine 4a was recovered in 8% yield as well.g There was no any reaction and the starting iodopyridine 4a was recovered in 89% yield.
1	1.5	5	5	DCM	r.t.	24	40^c
2	1.5	5	5	THF	r.t.	24	79^d
3	1.5	5	5	CH3CN	r.t.	24	78^e
4	1.5	5	5	Dioxane	r.t.	24	74^f
5	1.5	5	5	DMF	r.t.	24	83
6	1.5	5	5	DMSO	r.t.	24	82
7	1.5	5	5	DMF	65	1.5	91
8	1.5	5	5	DMF	100	1.5	76
9	1.0	5	5	DMF	65	1.5	68
10	2.0	5	5	DMF	65	1.5	91
11	1.5	—	5	DMF	65	1.5	^g
12	1.5	2	5	DMF	65	4.0	78
13	1.5	5	—	DMF	65	1.5	89

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Table 2 Synthesis of alkynylpyridines from iodopyridines via Sonogashira reaction

Entry	Iodopyridine	Alkyne	Alkynylpyridine	% yield^a	Entry	Iodopyridine	Alkyne	Alkynylpyridine	% yield^a
a Isolated yield.
1				91	10	4a			87
2	4a			98	11	4a			66
3	4a			95	12	4a			98
4	4a			57	13	4a			40
5	4a			72	14	4a			66
6	4a			92	15	4a			99
7	4a			95	16		6a		78
8	4a			80	17	4b	6b		99
9	4a			80	18	4b	6d		87
19	4b	6l		98	24	4c	6o		80
20	4b	6o		92	25		6a		84
21		6a		90	26		6a		85
22	4c	6b		75	27		6a		86
23	4c	6l		73	28		6a		91

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As depicted in Table 2, a diverse range of alkynylpyridines 7 were synthesized by employing a variety of iodopyridines 4 and terminal alkynes 6. In most cases, coupling reactions proceeded efficiently and afforded the corresponding alkynylpyridines 7 in good to excellent yields (57–99%), except that alkynylpyridine 7m bearing a pyridin-2-yl group as the alkyne substituent was obtained in 40% yield (Table 2, entry 13). It is noteworthy that the incorporation of fluorine-bearing substituents into organic compounds could result in beneficial biological properties.³⁵ So two derivatives of fluorine-containing alkynylpyridines, 7f and 7g, were synthesized in 92 and 95% yields, respectively (Table 2, entries 6 and 7). Thiophenes are commonly used as building blocks in many agrochemicals and pharmaceuticals as well as materials science.³⁶ Thus we also synthesized six derivatives of thiophen-3-yl- and/or thiophen-3-ylethynyl-substituted pyridines, 7l, 7s, 7u-7w and 7x, in 73–98% yields (Table 2, entries 12, 19, 21–23 and 24). Note that alkynylpyridine 7w has two thiophenyl groups in its structure (Table 2, entry 23). On the other hand, ferrocenyl-substituted alkynylpyridines may have great potential for biological and medicinal studies since, according to recent studies,³⁷ the combination of ferrocenyl group with biologically active molecules may enhance their current biological activities or create new medicinal properties. For this reason, three derivatives of ferrocenyl-substituted alkynylpyridines, 7o, 7t and 7x, were synthesized in 80–99% yields (Table 2, entries 15, 20 and 24). Note that alkynylpyridine 7x contains not only ferrocenyl group but also thiophenyl moiety in its structure (Table 2, entry 24). Furthermore, we synthesized five derivatives of alkynylpyridines bearing alkyl substituents, such as butyl, pentyl, cyclopentylmethyl, hydroxycyclohexyl and N-phthalimidylethyl groups, as the alkyne substituent, 7i–k and 7n, in 66–87% yields (Table 2, entries 8–11 and 14).

We also examined Sonogashira coupling of two commercially available iodopyridines 8 with phenylacetylene (6a) as shown in Table 3. The reaction of 3-iodo-2-methoxypyridine (8a) with phenylacetylene (6a) under the same conditions produced the expected 3-alkynylpyridine 9 in 90% yield (Table 3, entry 1). For the reaction of 2,3-diiodopyridine (8b), the amount of terminal alkyne employed was critical, and the reaction was performed in turn with 1.0, 1.5, 2.0 and 3.0 equivalents of phenylacetylene (6a) (Table 3, entries 2–5). When the reaction was carried out with 1.0 equiv. of phenylacetylene (6a), it afforded three products; 2-alkynylpyridine 10 (31%), 3-alkynylpyridine 11 (12%) and 2,3-dialkynylpyridine 12 (13%), of which the pyridine 10 was the major product (Table 3, entry 2). A similar trend was observed in the reaction with 1.5 equiv. of phenylacetylene (6a), where monoalkynylpyridines 10 (34%) and 11 (9%) and dialkynylpyridine 12 (32%) were obtained (Table 3, entry 3). In reactions with lower equivalents of terminal alkyne, coupling occurred at both α- and β-positions of pyridine ring, but predominantly at α-position, which is consistent with the earlier findings.³⁸ When 2.0 equiv. of phenylacetylene (6a) was employed, two products resulted from the reaction where the proportion of dialkynylpyridine 12 (72%) increased at the expense of alkynylpyridine 10 (17%) (Table 3, entry 4). When the reaction was performed with excess phenylacetylene (6a) such as 3.0 equiv., only dialkynylpyridine 12 was obtained in high yield (95%) (Table 3, entry 5). Notably, the reactions with higher equivalents of terminal alkyne afforded dialkynylpyridine 12 as the major or single product. Moreover, higher equivalents of terminal alkyne increased the overall yield of products.

Table 3 Synthesis of alkynylpyridines from other iodopyridines via Sonogashira reaction

Entry	Iodopyridine	Alkyne (equiv.)	Alkynylpyridine(s) (% yield^a)
a Isolated yield.
1	8a	6a (1.5 equiv.)	9 (90%)
2	8b	6a (1.0 equiv.)	10 (31%) + 11 (12%) + 12 (13%)
3	8b	6a (1.5 equiv.)	10 (34%) + 11 (9%) + 12 (32%)
4	8b	6a (2.0 equiv.)	10 (17%) + 12 (72%)
5	8b	6a (3.0 equiv.)	12 (95%)

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In brief, by using Sonogashira approach, we synthesized thirty new derivatives of alkynylpyridines from the corresponding iodopyridines and terminal alkynes in good to excellent yields as depicted in Tables 2 and 3.

3. Conclusions

In summary, we have synthesized iodopyridines and explored their Sonogashira coupling with terminal alkynes. The reactions were achieved by employing 5 mol% PdCl₂(PPh₃)₂, 5 mol% CuI, excess Et₃N and 1.5 equiv. of terminal alkyne, relative to starting iodopyridine, as well as heating in DMF at 65 °C. In fact, Sonogashira coupling reactions of iodopyridines with terminal alkynes proceeded well and afforded highly-substituted alkynylpyridines in good to excellent yields. The reactions were found to be general for a diverse range of iodopyridines and terminal alkynes, and allowed the presence of a variety of substituents with electron-withdrawing and electron-donating groups. These alkynylpyridines have great potential as well to undergo a variety of reactions via their triple bonds for further functionalization and derivatization. In conclusion, the chemistry developed here is very versatile and accommodates various functional groups, which can be used for the generation of the corresponding pyridine libraries. Besides, the synthesized alkynylpyridines have enormous potential to function as new pharmacophores and scaffolds in medicinal chemistry.

4. Experimental

4.1. General information

¹H and ¹³C NMR spectra were recorded at 400 and 100 MHz, respectively. Chemical shifts are reported relative to CDCl₃ (7.26 and 77.16 ppm in ¹H and ¹³C NMR, respectively). Coupling constants (J) are reported in Hertz (Hz), and spin multiplicities are presented by the following symbols: s (singlet), br s (broad singlet), d (doublet), t (triplet), q (quartet), m (multiplet). DEPT ¹³C NMR information is given in parentheses as C, CH, CH₂ and CH₃. Infrared spectra (IR) were recorded by using attenuated total reflection (ATR). Band positions are reported in reciprocal centimeters (cm⁻¹). Mass spectra (MS) and high resolution mass spectra (HRMS) were obtained by using electrospray ionization (ESI) with Micro-Tof; m/z values are reported (for each measurement, the mass scale was recalibrated with sodium formate clusters, and samples were dissolved and measured in MeOH or CH₃CN). Flash chromatography was performed using thick-walled glass columns and “flash grade” silica (230–400 mesh). Thin layer chromatography (TLC) was performed by using commercially prepared 0.25 mm silica gel plates and visualization was effected with short wavelength UV lamp (254 nm). The relative proportions of solvents in chromatography solvent mixtures refer to the volume : volume ratio. All commercially available reagents were used directly without purification unless otherwise stated. All the solvents used in reactions and chromatography were distilled and/or dried properly for purity. The inert atmosphere was created by slight positive pressure (ca. 0.1 psi) of argon. All glassware was dried in oven prior to use.

4.2. General procedure for the synthesis of alkynylpyridines 7 (Table 2) and 9–12 (Table 3)

In a two-neck round-bottom flask equipped with a reflux condenser, iodopyridine derivative 4 or 8 (0.20 mmol), PdCl₂(PPh₃)₂ (0.01 mmol) and CuI (0.01 mmol) were dissolved in a mixture of triethylamine (3.0 mL) and DMF (1.5 mL) by vigorous stirring under argon. Meanwhile, separately in a flask under argon, the corresponding terminal alkyne 6 (0.30 mmol) was dissolved in DMF (1.5 mL) and added slowly to the first reaction flask over 20 min (note that for the reactions in Table 3, the indicated equivalents of terminal alkyne, with respect to iodopyridine, were employed). Then the resulting reaction mixture was heated at 65 °C with stirring under argon. After the reaction was over, as indicated by the routine TLC analysis, the reaction mixture was transferred into a separatory funnel, and ethyl acetate (30 mL) and a saturated aqueous solution of NH₄Cl (20 mL) were added. After the layers were separated, the aqueous layer was extracted with ethyl acetate (2 × 30 mL). The combined organic layers were dried over MgSO₄ and evaporated on a rotary evaporator. The resulting crude product was purified by flash chromatography on silica gel using hexane/ethyl acetate (9 : 1 followed by 4 : 1) as eluent to afford the corresponding alkynylpyridine 7, 9, 10, 11 and/or 12.

(2,4-Diphenyl-5-(phenylethynyl)pyridin-3-yl)(phenyl)methanone (7a). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and phenylacetylene (6a) (30.6 mg, 0.30 mmol) were employed to afford 79.3 mg (91%) of the indicated product as a yellow solid (R_f = 0.53 in 4 : 1 hexane/ethyl acetate): mp 151.8–153.5 °C. ¹H NMR (400 MHz, CDCl₃) δ 9.06 (s, 1H), 7.60–7.52 (m, 4H), 7.41–7.36 (m, 1H), 7.35–7.21 (m, 15H); ¹³C NMR (100 MHz, CDCl₃) δ 196.4 (CO), 155.4 (C), 152.5 (CH), 150.4 (C), 139.1 (C), 137.6 (C), 135.9 (C), 133.8 (C), 133.3 (CH), 131.6 (CH), 129.6 (CH), 129.4 (CH), 129.3 (CH), 129.0 (CH), 128.9 (CH), 128.5 (CH), 128.42 (CH), 128.38 (2 × CH), 127.9 (CH), 122.6 (C), 119.0 (C), 96.6 (C), 85.5 (C); IR (neat): 3056, 3025, 2960, 2922, 2214, 1669, 1593, 1578, 1553, 1516, 1489, 1434, 1377, 1323, 1286, 1259, 1221, 1176, 1095, 1071, 1016, 1003, 921, 873, 801, 770, 701, 686, 670, 640, 529, 514 cm⁻¹; MS (ESI, m/z): 436.17 [M + H]⁺; HRMS (ESI): calcd for C₃₂H₂₂NO: 436.1695 [M + H]⁺, found: 436.1692.

(2,4-Diphenyl-5-(p-tolylethynyl)pyridin-3-yl)(phenyl)methanone (7b). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 4-ethynyltoluene (6b) (34.8 mg, 0.30 mmol) were employed to afford 88.1 mg (98%) of the indicated product as a yellow solid (R_f = 0.57 in 4 : 1 hexane/ethyl acetate): mp 170.3–174.5 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.93 (s, 1H), 7.48–7.41 (m, 4H), 7.27 (t, J = 7.4 Hz, 1H), 7.22–7.09 (m, 10H), 7.05 (d, 8.4 Hz, 2H), 6.99 (d, 8.0 Hz, 2H), 2.24 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 196.5 (CO), 155.3 (C), 152.5 (CH), 150.2 (C), 139.2 (C), 139.1 (C), 137.6 (C), 136.0 (C), 133.8 (C), 133.3 (CH), 131.5 (CH), 129.6 (CH), 129.4 (CH), 129.3 (CH), 129.2 (CH), 128.9 (CH), 128.5 (CH), 128.4 (2 × CH), 127.9 (CH), 119.6 (C), 119.2 (C), 96.9 (C), 84.9 (C), 21.6 (CH₃); IR (neat): 3053, 3025, 2215, 2197, 1671, 1597, 1579, 1553, 1508, 1438, 1315, 1262, 1226, 1175, 1161, 1074, 993, 875, 813, 767, 756, 696, 671, 655, 638, 577, 529, 507 cm⁻¹; MS (ESI, m/z): 450.18 [M + H]⁺; HRMS (ESI): calcd for C₃₃H₂₄NO: 450.1852 [M + H]⁺, found: 450.1847.

(2,4-Diphenyl-5-(m-tolylethynyl)pyridin-3-yl)(phenyl)methanone (7c). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 3-ethynyltoluene (6c) (34.8 mg, 0.30 mmol) were employed to afford 85.4 mg (95%) of the indicated product as an orange solid (R_f = 0.47 in 4 : 1 hexane/ethyl acetate): mp 126.4–129.5 °C. ¹H NMR (400 MHz, CDCl₃) δ 9.05 (s, 1H), 7.59–7.54 (m, 4H), 7.39 (tt, J = 7.4 and 1.2 Hz, 1H), 7.34–7.20 (m, 10H), 7.18 (d, J = 7.6 Hz, 1H), 7.13 (d, J = 7.6 Hz, 1H), 7.08 (s, 1H), 7.05 (d, J = 7.2 Hz, 1H), 2.32 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 196.5 (CO), 155.4 (C), 152.6 (CH), 150.3 (C), 139.1 (C), 138.1 (C), 137.6 (C), 135.9 (C), 133.8 (C), 133.4 (CH), 132.2 (CH), 129.8 (CH), 129.6 (CH), 129.5 (CH), 129.4 (CH), 129.2 (CH), 129.0 (CH), 128.7 (CH), 128.5 (CH), 128.4 (CH), 128.3 (CH), 127.9 (CH), 122.4 (C), 119.1 (C), 96.9 (C), 85.2 (C), 21.3 (CH₃); IR (neat): 3058, 3024, 2208, 1734, 1669, 1593, 1578, 1552, 1515, 1483, 1447, 1438, 1375, 1324, 1314, 1284, 1260, 1232, 1205, 1175, 1000, 910, 849, 784, 770, 758, 699, 670, 640, 593, 517 cm⁻¹; MS (ESI, m/z): 450.19 [M + H]⁺; HRMS (ESI): calcd for C₃₃H₂₄NO: 450.1852 [M + H]⁺, found: 450.1862.

(5-((4-Methoxyphenyl)ethynyl)-2,4-diphenylpyridin-3-yl)(phenyl)methanone (7d). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 4-ethynylanisole (6d) (39.6 mg, 0.30 mmol) were employed to afford 53.1 mg (57%) of the indicated product as a yellow solid (R_f = 0.37 in 4 : 1 hexane/ethyl acetate): mp 181.5–184.3 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.92 (s, 1H), 7.49–7.41 (m, 4H), 7.27 (tt, J = 7.4 and 1.2 Hz, 1H), 7.23–7.09 (m, 10H), 7.10–7.05 (m, 2H), 6.74–6.69 (m, 2H), 3.70 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 196.5 (CO), 160.2 (CO), 155.1 (C), 152.3 (CH), 150.1 (C), 139.2 (C), 137.6 (C), 136.1 (C), 133.8 (C), 133.3 (CH), 133.2 (CH), 129.6 (CH), 129.4 (CH), 129.3 (CH), 128.9 (CH), 128.5 (CH), 128.4 (2 × CH), 127.9 (CH), 119.4 (C), 114.7 (C), 114.1 (CH), 96.9 (C), 84.4 (C), 55.4 (CH₃); IR (neat): 3054, 3025, 2962, 2936, 2217, 1671, 1602, 1509, 1441, 1292, 1254, 1227, 1174, 1162, 1030, 992, 877, 833, 807, 768, 757, 697, 672, 534, 509 cm⁻¹; MS (ESI, m/z): 466.18 [M + H]⁺; HRMS (ESI): calcd for C₃₃H₂₄NO₂: 466.1802 [M + H]⁺, found: 466.1802.

(5-((4-(Dimethylamino)phenyl)ethynyl)-2,4-diphenylpyridin-3-yl)(phenyl)methanone (7e). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 4-ethynyl-N,N-dimethylaniline (6e) (43.6 mg, 0.30 mmol) were employed to afford 68.9 mg (72%) of the indicated product as a yellow solid (R_f = 0.33 in 4 : 1 hexane/ethyl acetate): mp 178.5–181.0 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.90 (s, 1H), 7.48–7.42 (m, 4H), 7.26 (t, J = 7.4 Hz, 1H), 7.22–7.09 (m, 10H), 7.00 (d, J = 9.2 Hz, 2H), 6.47 (d, J = 8.9 Hz, 2H), 2.86 (s, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 196.7 (CO), 154.5 (C), 152.1 (CH), 150.5 (C), 149.5 (C), 139.3 (C), 137.7 (C), 136.2 (C), 133.7 (C), 133.2 (CH), 132.8 (2 × CH), 129.7 (CH), 129.4 (CH), 129.2 (CH), 128.8 (CH), 128.3 (2 × CH), 127.8 (CH), 119.9 (C), 111.8 (CH), 109.2 (C), 98.5 (C), 83.8 (C), 40.2 (CH₃); IR (neat): 2914, 2853, 2802, 2187, 1669, 1579, 1549, 1522, 1491, 1442, 1370, 1332, 1315, 1287, 1262, 1228, 1200, 1155, 1129, 1072, 1030, 1011, 991, 945, 873, 810, 766, 755, 694, 649, 636, 578, 525, 514 cm⁻¹; MS (ESI, m/z): 479.21 [M + H]⁺; HRMS (ESI): calcd for C₃₄H₂₇N₂O: 479.2118 [M + H]⁺, found: 479.2133.

(2,4-Diphenyl-5-((4-(trifluoromethyl)phenyl)ethynyl)pyridin-3-yl)(phenyl)methanone (7f). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 4-ethynyl-α,α,α-trifluorotoluene (6f) (51.0 mg, 0.30 mmol) were employed to afford 92.6 mg (92%) of the indicated product as a red solid (R_f = 0.43 in 4 : 1 hexane/ethyl acetate): mp 158.1–159.7 °C. ¹H NMR (400 MHz, CDCl₃) δ 9.07 (s, 1H), 7.61–7.52 (m, 6H), 7.39 (tt, J = 7.4 and 1.2 Hz, 1H), 7.35–7.27 (m, 10H), 7.24 (t, J = 7.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 196.3 (CO), 156.0 (C), 152.6 (CH), 150.9 (C), 139.0 (C), 137.5 (C), 135.8 (C), 133.9 (C), 133.5 (CH), 131.8 (CH), 130.5 (q, ²J = 32.0 Hz, C), 129.5 (CH), 129.4 (CH), 129.3 (CH), 129.2 (CH), 128.7 (CH), 128.47 (CH), 128.45 (CH), 128.0 (CH), 126.4 (C), 125.4 (q, ³J = 3.8 Hz, CH), 123.9 (q, ¹J = 271.2 Hz, CF₃), 118.4 (C), 95.0 (C), 87.8 (C); IR (neat): 3056, 3027, 2325, 1668, 1613, 1596, 1579, 1515, 1495, 1437, 1404, 1377, 1329, 1287, 1223, 1165, 1121, 1105, 1064, 1015, 1002, 921, 875, 840, 767, 755, 715, 696, 672, 596, 576, 523 cm⁻¹; MS (ESI, m/z): 504.16 [M + H]⁺; HRMS (ESI): calcd for C₃₃H₂₁F₃NO: 504.1570 [M + H]⁺, found: 504.1564.

(5-((3-Fluorophenyl)ethynyl)-2,4-diphenylpyridin-3-yl)(phenyl)methanone (7g). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 1-ethynyl-3-fluorobenzene (6g) (36.0 mg, 0.30 mmol) were employed to afford 86.2 mg (95%) of the indicated product as a yellow solid (R_f = 0.43 in 4 : 1 hexane/ethyl acetate): mp 132.1–135.6 °C. ¹H NMR (400 MHz, CDCl₃) δ 9.05 (s, 1H), 7.62–7.53 (m, 4H), 7.39 (tt, J = 7.4 and 1.2 Hz, 1H), 7.34–7.21 (m, 11H), 7.06–6.99 (m, 2H), 6.92 (ddd, J = 9.3, 2.4 and 1.5 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 196.3 (CO), 162.4 (d, ¹J = 245.6 Hz, CF), 155.8 (C), 152.6 (CH), 150.6 (C), 139.0 (C), 137.5 (C), 135.8 (C), 133.9 (C), 133.4 (CH), 130.0 (d, ³J = 8.4 Hz, CH), 129.5 (CH), 129.4 (CH), 129.3 (CH), 129.1 (CH), 128.7 (CH), 128.4 (2 × CH), 128.0 (CH), 127.5 (d, ⁴J = 2.9 Hz, CH), 124.4 (d, ³J = 9.4 Hz, C), 118.5 (C), 118.3 (d, ²J = 22.7 Hz, CH), 116.2 (d, ²J = 21.4 Hz, CH), 95.2 (d, ⁴J = 3.5 Hz, C), 86.4 (C); IR (neat): 3061, 3027, 2213, 1670, 1605, 1593, 1577, 1553, 1486, 1448, 1427, 1315, 1260, 1232, 1206, 1176, 1134, 1005, 932, 873, 854, 786, 770, 757, 741, 699, 680, 661, 592, 517 cm⁻¹; MS (ESI, m/z): 454.16 [M + H]⁺; HRMS (ESI): calcd for C₃₂H₂₁FNO: 454.1602 [M + H]⁺, found: 454.1619.

(5-(Hex-1-yn-1-yl)-2,4-diphenylpyridin-3-yl)(phenyl)methanone (7h). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 1-hexyne (6h) (24.6 mg, 0.30 mmol) were employed to afford 66.5 mg (80%) of the indicated product as a light yellow solid (R_f = 0.52 in 4 : 1 hexane/ethyl acetate): mp 107.5–109.1 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.91 (s, 1H), 7.55–7.49 (m, 4H), 7.39–7.34 (m, 1H), 7.27–7.18 (m, 10H), 2.28 (t, J = 6.9 Hz, 2H), 1.37 (quintet, J = 7.2 Hz, 2H), 1.21 (sextet, J = 7.2 Hz, 2H), 0.83 (t, J = 7.3 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 196.6 (CO), 154.7 (C), 152.9 (CH), 150.2 (C), 139.2 (C), 137.7 (C), 136.1 (C), 133.7 (C), 133.3 (CH), 129.4 (2 × CH), 129.2 (CH), 128.8 (CH), 128.3 (CH), 128.3 (CH), 128.3 (CH), 127.8 (CH), 119.6 (C), 98.2 (C), 76.5 (C), 30.3 (CH₂), 21.7 (CH₂), 19.3 (CH₂), 13.7 (CH₃); IR (neat): 3053, 2955, 2926, 2855, 2224, 1668, 1635, 1593, 1579, 1555, 1519, 1495, 1449, 1435, 1378, 1318, 1291, 1260, 1214, 1175, 1077, 1025, 1000, 934, 926, 846, 799, 768, 754, 701, 689, 664, 587, 517 cm⁻¹; MS (ESI, m/z): 416.20 [M + H]⁺; HRMS (ESI): calcd for C₃₀H₂₆NO: 416.2009 [M + H]⁺, found: 416.202.

(5-(Hept-1-yn-1-yl)-2,4-diphenylpyridin-3-yl)(phenyl)methanone (7i). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 1-heptyne (6i) (28.9 mg, 0.30 mmol) were employed to afford 68.7 mg (80%) of the indicated product as a yellow solid (R_f = 0.63 in 4 : 1 hexane/ethyl acetate): mp 117.1–120.4 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.81 (s, 1H), 7.46–7.39 (m, 4H), 7.27 (t, J = 7.4 Hz, 1H), 7.18–7.08 (m, 10H), 2.17 (t, J = 6.9 Hz, 2H), 1.30 (quintet, J = 7.2 Hz, 2H), 1.20–1.06 (m, 4H), 0.76 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 196.6 (CO), 154.8 (C), 153.0 (CH), 150.2 (C), 139.2 (C), 137.7 (C), 136.1 (C), 133.7 (C), 133.3 (CH), 129.4 (2 × CH), 129.2 (CH), 128.8 (CH), 128.4 (CH), 128.3 (2 × CH), 127.8 (CH), 119.7 (C), 98.3 (C), 76.6 (C), 30.9 (CH₂), 28.0 (CH₂), 22.3 (CH₂), 19.6 (CH₂), 14.0 (CH₃); IR (neat): 2952, 2923, 2855, 2223, 1667, 1593, 1578, 1554, 1519, 1495, 1448, 1434, 1377, 1317, 1290, 1260, 1213, 1175, 1076, 1042, 1024, 1000, 934, 799, 769, 753, 716, 688, 664, 612, 586, 511 cm⁻¹; MS (ESI, m/z): 430.22 [M + H]⁺; HRMS (ESI): calcd for C₃₁H₂₈NO: 430.2165 [M + H]⁺, found: 430.2163.

(5-(3-Cyclopentylprop-1-yn-1-yl)-2,4-diphenylpyridin-3-yl)(phenyl)methanone (7j). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 3-cyclopentyl-1-propyne (6j) (32.5 mg, 0.30 mmol) were employed to afford 76.8 mg (87%) of the indicated product as an orange solid (R_f = 0.63 in 4 : 1 hexane/ethyl acetate): mp 132.8–135.3 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.81 (s, 1H), 7.46–7.38 (m, 4H), 7.28–7.23 (m, 1H), 7.19–7.07 (m, 10H), 2.19 (d, J = 6.6 Hz, 2H), 1.86–1.74 (m, 1H), 1.54–1.34 (m, 6H), 1.03–0.92 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 196.6 (CO), 154.7 (C), 153.0 (CH), 150.2 (C), 139.2 (C), 137.6 (C), 136.1 (C), 133.7 (C), 133.2 (CH), 129.4 (CH), 129.4 (CH), 129.2 (CH), 128.8 (CH), 128.32 (CH), 128.30 (CH), 128.2 (CH), 127.8 (CH), 119.7 (C), 97.7 (C), 76.6 (C), 38.8 (CH), 31.8 (CH₂), 25.3 (CH₂), 25.2 (CH₂); IR (neat): 3063, 3026, 2947, 2861, 2218, 1668, 1593, 1578, 1550, 1518, 1493, 1448, 1432, 1375, 1317, 1292, 1259, 1212, 1176, 1095, 1077, 1040, 1024, 1000, 928, 843, 800, 769, 755, 718, 688, 642, 584, 515 cm⁻¹; MS (ESI, m/z): 442.22 [M + H]⁺; HRMS (ESI): calcd for C₃₂H₂₈NO: 442.2165 [M + H]⁺, found: 442.2179.

(5-((1-Hydroxycyclohexyl)ethynyl)-2,4-diphenylpyridin-3-yl)(phenyl)methanone (7k). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 1-ethynyl-1-cyclohexanol (6k) (37.3 mg, 0.30 mmol) were employed to afford 60.4 mg (66%) of the indicated product as a yellow solid (R_f = 0.07 in 4 : 1 hexane/ethyl acetate): mp 181.9–185.0 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.93 (s, 1H), 7.46–7.37 (m, 4H), 7.27 (t, J = 7.4 Hz, 1H), 7.20–7.08 (m, 10H), 2.96 (br s, 1H), 1.65 (d, J = 10.7 Hz, 2H), 1.46–1.16 (m, 6H), 0.99 (d, J = 7.2 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 196.3 (CO), 155.3 (C), 152.6 (CH), 150.8 (C), 138.8 (C), 137.5 (C), 135.9 (C), 133.9 (C), 133.4 (CH), 129.4 (CH), 129.3 (2 × CH), 129.0 (CH), 128.4 (CH), 128.4 (2 × CH), 127.9 (CH), 118.8 (C), 100.8 (C), 80.1 (C), 69.1 (C), 39.7 (CH₂), 25.1 (CH₂), 23.1 (CH₂); IR (neat): 3270, 2956, 2857, 2199, 1664, 1591, 1579, 1557, 1523, 1438, 1408, 1314, 1297, 1259, 1210, 1083, 1057, 1029, 1015, 968, 934, 871, 802, 766, 692, 648, 638, 580 cm⁻¹; MS (ESI, m/z): 458.21 [M + H]⁺; HRMS (ESI): calcd for C₃₂H₂₈NO₂: 458.2115 [M + H]⁺, found: 458.2127.

(2,4-Diphenyl-5-(thiophen-3-ylethynyl)pyridin-3-yl)(phenyl)methanone (7l). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 3-ethynylthiophene (6l) (32.4 mg, 0.30 mmol) were employed to afford 86.5 mg (98%) of the indicated product as a light yellow solid (R_f = 0.50 in 4 : 1 hexane/ethyl acetate): mp 147.5–149.2 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.92 (s, 1H), 7.48–7.42 (m, 4H), 7.31–7.25 (m, 1H), 7.22–7.11 (m, 12H), 6.83 (dd, J = 5.0 and 1.1 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 196.4 (CO), 155.3 (C), 152.4 (CH), 150.2 (C), 139.1 (C), 137.5 (C), 135.9 (C), 133.8 (C), 133.3 (CH), 129.6 (CH), 129.5 (CH), 129.4 (CH), 129.4 (CH), 129.2 (CH), 128.9 (CH), 128.5 (CH), 128.4 (2 × CH), 127.9 (CH), 125.6 (CH), 121.7 (C), 119.0 (C), 91.9 (C), 85.1 (C); IR (neat): 3093, 3061, 2209, 1668, 1593, 1578, 1555, 1514, 1493, 1448, 1437, 1375, 1361, 1316, 1285, 1259, 1224, 1210, 1176, 1080, 1004, 931, 856, 796, 769, 757, 694, 684, 630, 594, 511 cm⁻¹; MS (ESI, m/z): 442.13 [M + H]⁺; HRMS (ESI): calcd for C₃₀H₂₀NOS: 442.1260 [M + H]⁺, found: 442.1262.

(2,4-Diphenyl-5-(pyridin-2-ylethynyl)pyridin-3-yl)(phenyl)methanone (7m). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 2-ethynylpyridine (6m) (30.9 mg, 0.30 mmol) were employed to afford 34.9 mg (40%) of the indicated product as a brown solid (R_f = 0.03 in 4 : 1 hexane/ethyl acetate): mp 160.9–163.8 °C. ¹H NMR (400 MHz, CDCl₃) δ 9.05 (s, 1H), 8.50 (d, J = 4.3 Hz, 1H), 7.53–7.41 (m, 5H), 7.29 (t, J = 7.4 Hz, 1H), 7.25–7.11 (m, 11H), 6.96 (d, J = 7.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 196.3 (CO), 156.2 (C), 153.2 (CH), 150.9 (C), 150.1 (CH), 142.9 (C), 139.0 (C), 137.5 (C), 136.3 (CH), 135.7 (C), 133.9 (CH), 133.4 (CH), 129.6 (CH), 129.5 (CH), 129.3 (CH), 129.1 (CH), 128.7 (CH), 128.4 (2 × CH), 128.0 (CH), 127.6 (CH), 123.2 (C), 118.0 (C), 95.2 (C), 85.3 (C); IR (neat): 3066, 2958, 2920, 2850, 1670, 1593, 1577, 1560, 1553, 1517, 1492, 1462, 1436, 1423, 1377, 1329, 1314, 1286, 1260, 1224, 1173, 1079, 1026, 1005, 985, 931, 876, 802, 776, 756, 698, 629, 511 cm⁻¹; MS (ESI, m/z): 437.17 [M + H]⁺; HRMS (ESI): calcd for C₃₁H₂₁N₂O: 437.1648 [M + H]⁺, found: 437.1658.

2-(4-(5-Benzoyl-4,6-diphenylpyridin-3-yl)but-3-yn-1-yl)isoindoline-1,3-dione (7n). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and N-(3-butynyl)phthalimide (6n) (59.8 mg, 0.30 mmol) were employed to afford 70.3 mg (66%) of the indicated product as a yellowish brown solid (R_f = 0.10 in 4 : 1 hexane/ethyl acetate): mp 340.0 °C (decomp.). ¹H NMR (400 MHz, CDCl₃) δ 8.76 (s, 1H), 7.83–7.74 (m, 2H), 7.70–7.63 (m, 2H), 7.45–7.35 (m, 4H), 7.27 (t, J = 7.4 Hz, 1H), 7.20–7.00 (m, 10H), 3.70 (t, J = 7.0 Hz, 2H), 2.60 (t, J = 7.0 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 196.5 (CO), 168.0 (CO), 155.2 (C), 153.2 (CH), 150.3 (C), 139.1 (C), 137.6 (C), 135.8 (C), 134.2 (CH), 133.7 (C), 133.3 (C), 132.1 (CH), 129.4 (CH), 129.3 (CH), 129.2 (CH), 128.9 (CH), 128.4 (CH), 128.3 (CH), 128.3 (CH), 127.8 (CH), 123.5 (CH), 118.8 (C), 93.3 (C), 78.2 (C), 36.5 (CH₂), 19.6 (CH₂); IR (neat): 3057, 2924, 2853, 2232, 1772, 1708, 1668, 1595, 1580, 1555, 1521, 1495, 1436, 1393, 1361, 1303, 1241, 1214, 1188, 1158, 1112, 1074, 1044, 998, 961, 939, 892, 867, 735, 717, 695, 625, 582, 529 cm⁻¹; MS (ESI, m/z): 533.19 [M + H]⁺; HRMS (ESI): calcd for C₃₆H₂₅N₂O₃: 533.1860 [M + H]⁺, found: 533.1856.

5-(Ferrocenylethynyl)-(2,4-diphenylpyridin-3-yl)(phenyl)methanone (7o). (5-Iodo-2,4-diphenylpyridin-3-yl)(phenyl)methanone (4a) (92.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and ethynylferrocene (6o) (63.0 mg, 0.30 mmol) were employed to afford 107.6 mg (99%) of the indicated product as a red solid (R_f = 0.55 in 4 : 1 hexane/ethyl acetate): mp 190.9–194.0 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.87 (s, 1H), 7.50–7.40 (m, 4H), 7.26 (t, J = 7.4 Hz, 1H), 7.23–7.09 (m, 10H), 4.19 (t, J = 1.8 Hz, 2H), 4.11–4.07 (m, 2H), 3.93 (s, 5H); ¹³C NMR (100 MHz, CDCl₃) δ 196.5 (CO), 154.7 (C), 152.3 (CH), 149.9 (C), 139.2 (C), 137.6 (C), 136.3 (C), 133.8 (C), 133.3 (CH), 129.44 (CH), 129.38 (CH), 129.2 (CH), 128.8 (CH), 128.4 (CH), 128.3 (2 × CH), 127.9 (CH), 119.6 (C), 96.4 (C), 81.6 (C), 71.4 (CH), 70.1 (CH), 69.2 (CH), 64.1 (C); IR (neat): 3026, 2961, 2214, 1655, 1596, 1580, 1555, 1515, 1495, 1469, 1430, 1413, 1318, 1262, 1228, 1174, 1106, 1044, 1028, 1000, 971, 916, 823, 814, 772, 756, 729, 710, 695, 643, 602, 574, 523, 497, 484, 460 cm⁻¹; MS (ESI, m/z): 542.15 [M + H]⁺; HRMS (ESI): calcd For C₃₆H₂₆⁵⁴FeNO: 542.1405 [M + H]⁺, found: 542.1466.

(2-(4-Methoxyphenyl)-4-phenyl-5-(phenylethynyl)pyridin-3-yl)(phenyl)methanone (7p). (5-Iodo-2-(4-methoxyphenyl)-4-phenylpyridin-3-yl)(phenyl)methanone (4b) (98.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and phenylacetylene (6a) (30.6 mg, 0.30 mmol) were employed to afford 72.6 mg (78%) of the indicated product as a yellow solid (R_f = 0.33 in 4 : 1 hexane/ethyl acetate): mp 154.1–155.5 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.91 (s, 1H), 7.48–7.41 (m, 4H), 7.28 (t, J = 7.4 Hz, 1H), 7.22–7.10 (m, 12H), 6.72–6.68 (m, 2H), 3.65 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 196.8 (CO), 160.3 (CO), 155.0 (C), 152.5 (CH), 150.4 (C), 137.6 (C), 136.0 (C), 133.4 (CH), 131.7 (C), 131.6 (CH), 130.7 (CH), 129.6 (C), 129.5 (CH), 129.4 (CH), 128.8 (CH), 128.5 (CH), 128.4 (2 × CH), 127.9 (CH), 122.7 (C), 118.4 (C), 113.9 (CH), 96.4 (C), 85.6 (C), 55.3 (CH₃); IR (neat): 3019, 2965, 2933, 2839, 2219, 1665, 1609, 1595, 1578, 1515, 1489, 1437, 1416, 1378, 1320, 1248, 1225, 1175, 1110, 1072, 1022, 1002, 929, 874, 841, 812, 760, 732, 699, 679, 639, 584, 522 cm⁻¹; MS (ESI, m/z): 466.18 [M + H]⁺; HRMS (ESI): calcd for C₃₃H₂₄NO₂: 466.1802 [M + H]⁺, found: 466.1820.

(2-(4-Methoxyphenyl)-4-phenyl-5-(p-tolylethynyl)pyridin-3-yl)(phenyl)methanone (7q). (5-Iodo-2-(4-methoxyphenyl)-4-phenylpyridin-3-yl)(phenyl)methanone (4b) (98.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 4-ethynyltoluene (6b) (34.8 mg, 0.30 mmol) were employed to afford 95.0 mg (99%) of the indicated product as a yellow solid (R_f = 0.33 in 4 : 1 hexane/ethyl acetate): mp 167.2–169.4 °C. ¹H NMR (400 MHz, CDCl₃) δ 9.01 (s, 1H), 7.54 (dt, J = 5.8 and 5.3 Hz, 4H), 7.42–7.36 (m, 1H), 7.32–7.21 (m, 7H), 7.16–7.07 (m, 4H), 6.84–6.78 (m, 2H), 3.75 (s, 3H), 2.34 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 196.8 (CO), 160.2 (CO), 154.8 (C), 152.4 (CH), 150.2 (C), 139.0 (C), 137.6 (C), 136.0 (C), 133.4 (CH), 133.3 (C), 131.7 (C), 131.5 (CH), 130.7 (CH), 129.6 (CH), 129.4 (CH), 129.2 (CH), 128.4 (2 × CH), 127.8 (CH), 119.6 (C), 118.6 (C), 113.9 (CH), 96.7 (C), 85.0 (C), 55.3 (CH₃), 21.6 (CH₃); IR (neat): 3031, 3004, 2933, 2810, 2219, 1614, 1594, 1577, 1509, 1492, 1438, 1379, 1318, 1291, 1247, 1225, 1177, 1044, 1028, 992, 875, 842, 819, 764, 698, 623, 583, 532, 515 cm⁻¹; MS (ESI, m/z): 480.20 [M + H]⁺; HRMS (ESI): calcd for C₃₄H₂₆NO₂: 480.1958 [M + H]⁺, found: 480.1975.

(2-(4-Methoxyphenyl)-5-((4-methoxyphenyl)ethynyl)-4-phenylpyridin-3-yl)(phenyl)methanone (7r). (5-Iodo-2-(4-methoxyphenyl)-4-phenylpyridin-3-yl)(phenyl)methanone (4b) (98.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 4-ethynylanisole (6d) (39.6 mg, 0.30 mmol) were employed to afford 86.2 mg (87%) of the indicated product as a yellow solid (R_f = 0.20 in 4 : 1 hexane/ethyl acetate): mp 179.0–180.0 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.99 (s, 1H), 7.57–7.50 (m, 4H), 7.39 (t, J = 7.4 Hz, 1H), 7.29–7.22 (m, 7H), 7.19–7.14 (m, 2H), 6.84–6.77 (m, 4H), 3.81 (s, 3H), 3.76 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 196.8 (CO), 160.2 (C), 160.1 (C), 154.6 (C), 152.2 (CH), 150.0 (C), 137.63 (C), 137.61 (C), 136.1 (C), 133.3 (CH), 133.1 (CH), 131.7 (C), 130.7 (CH), 129.6 (CH), 129.4 (CH), 128.4 (2 × CH), 127.8 (CH), 118.8 (C), 114.8 (C), 114.1 (CH), 113.9 (CH), 96.7 (C), 84.5 (C), 55.4 (CH₃), 55.3 (CH₃); IR (neat): 2957, 2933, 2835, 2200, 1666, 1603, 1578, 1508, 1437, 1416, 1377, 1289, 1246, 1224, 1173, 1129, 1108, 1028, 1001, 931, 876, 831, 808, 790, 761, 698, 677, 579, 535 cm⁻¹; MS (ESI, m/z): 496.19 [M + H]⁺; HRMS (ESI): calcd for C₃₄H₂₆NO₃: 496.1907 [M + H]⁺, found: 496.1921.

(2-(4-Methoxyphenyl)-4-phenyl-5-(thiophen-3-ylethynyl)pyridin-3-yl)(phenyl)methanone (7s). (5-Iodo-2-(4-methoxyphenyl)-4-phenylpyridin-3-yl)(phenyl)methanone (4b) (98.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 3-ethynylthiophene (6l) (32.4 mg, 0.30 mmol) were employed to afford 92.4 mg (98%) of the indicated product as an orange solid (R_f = 0.30 in 4 : 1 hexane/ethyl acetate): mp 139.5–140.5 °C. ¹H NMR (400 MHz, CDCl₃) δ 9.00 (s, 1H), 7.58–7.51 (m, 4H), 7.42–7.36 (m, 1H), 7.31–7.21 (m, 9H), 6.92 (dd, J = 5.0 and 1.1 Hz, 1H), 6.82–6.78 (m, 2H), 3.75 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 196.8 (CO), 160.3 (CO), 154.9 (C), 152.3 (CH), 150.3 (C), 137.6 (C), 136.0 (C), 133.38 (CH), 133.35 (C), 131.7 (C), 130.7 (CH), 129.7 (CH), 129.5 (CH), 129.4 (CH), 129.3 (CH), 128.4 (2 × CH), 127.9 (CH), 125.6 (CH), 121.8 (C), 118.4 (C), 113.9 (CH), 91.7 (C), 85.2 (C), 55.3 (CH₃); IR (neat): 3106, 2951, 2926, 2834, 2228, 1658, 1596, 1575, 1510, 1491, 1438, 1409, 1304, 1294, 1247, 1223, 1206, 1172, 1110, 1029, 1018, 929, 834, 820, 785, 767, 715, 697, 677, 624, 534 cm⁻¹; MS (ESI, m/z): 472.14 [M + H]⁺; HRMS (ESI): calcd for C₃₁H₂₂NO₂S: 472.1366 [M + H]⁺, found: 472.1386.

(5-(Ferrocenylethynyl)-2-(4-methoxyphenyl)-4-phenylpyridin-3-yl)(phenyl)methanone (7t). (5-Iodo-2-(4-methoxyphenyl)-4-phenylpyridin-3-yl)(phenyl)methanone (4b) (98.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and ethynylferrocene (6o) (63.0 mg, 0.30 mmol) were employed to afford 105.5 mg (92%) of the indicated product as a red solid (R_f = 0.33 in 4 : 1 hexane/ethyl acetate): mp 175.1–178.8 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.85 (s, 1H), 7.44 (t, J = 8.6 Hz, 4H), 7.29 (t, J = 7.4 Hz, 1H), 7.24–7.16 (m, 5H), 7.14 (t, J = 7.7 Hz, 2H), 6.69 (d, J = 8.8 Hz, 2H), 4.21–4.17 (m, 2H), 4.11–4.08 (m, 2H), 3.93 (s, 5H), 3.64 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 196.8 (CO), 160.2 (C), 154.3 (C), 152.3 (CH), 150.0 (C), 137.6 (C), 136.4 (C), 133.4 (CH), 133.3 (C) 131.8 (C), 130.7 (CH), 129.4 (2 × CH), 128.4 (2 × CH), 127.9 (CH), 119.1 (C), 113.4 (CH), 96.1 (C), 81.7 (C), 71.4 (CH), 70.1 (CH), 69.2 (CH), 64.2 (C), 55.3 (CH₃); IR (neat): 2958, 2931, 2836, 2211, 1664, 1607, 1578, 1555, 1512, 1466, 1449, 1429, 1416, 1374, 1320, 1307, 1245, 1228, 1175, 1107, 1041, 1027, 999, 917, 822, 792, 695, 676, 647, 585, 569, 536, 486 cm⁻¹; MS (ESI, m/z): 572.16 [M + H]⁺; HRMS (ESI): calcd for C₃₇H₂₈⁵⁴FeNO₂: 572.1511 [M + H]⁺, found: 572.1584.

Phenyl(4-phenyl-5-(phenylethynyl)-2-(thiophen-3-yl)pyridin-3-yl)methanone (7u). (5-Iodo-4-phenyl-2-(thiophen-3-yl)pyridin-3-yl)(phenyl)methanone (4c) (93.5 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and phenylacetylene (6a) (30.6 mg, 0.30 mmol) were employed to afford 79.5 mg (90%) of the indicated product as a yellow solid (R_f = 0.50 in 4 : 1 hexane/ethyl acetate): mp 177.1–181.2 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.89 (s, 1H), 7.51–7.47 (m, 2H), 7.46 (dd, J = 2.9 and 1.3 Hz, 1H), 7.35–7.29 (m, 2H), 7.24–7.14 (m, 10H), 7.12 (ddd, J = 5.1, 3.0 and 1.6 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 196.9 (CO), 152.5 (CH), 150.2 (C), 149.9 (C), 140.3 (C), 137.4 (C), 135.8 (C), 133.6 (CH), 133.0 (C), 131.6 (CH), 129.6 (CH), 129.4 (CH), 128.8 (CH), 128.6 (CH), 128.54 (CH), 128.48 (CH), 128.4 (CH), 127.9 (CH), 127.0 (CH), 125.8 (CH), 122.7 (C), 118.7 (C), 96.6 (C), 85.6 (C); IR (neat): 3057, 3027, 2211, 1734, 1669, 1594, 1578, 1555, 1526, 1490, 1440, 1346, 1324, 1285, 1257, 1223, 1174, 1158, 1078, 1002, 908, 878, 867, 783, 765, 703, 686, 674, 641, 622, 522 cm⁻¹; MS (ESI, m/z): 442.13 [M + H]⁺; HRMS (ESI): calcd for C₃₀H₂₀NOS: 442.1260 [M + H]⁺, found: 442.1283.

Phenyl(4-phenyl-2-(thiophen-3-yl)-5-(p-tolylethynyl)pyridin-3-yl)methanone (7v). (5-Iodo-4-phenyl-2-(thiophen-3-yl)pyridin-3-yl)(phenyl)methanone (4c) (93.5 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 4-ethynyltoluene (6b) (34.8 mg, 0.30 mmol) were employed to afford 68.3 mg (75%) of the indicated product as a yellow solid (R_f = 0.48 in 4 : 1 hexane/ethyl acetate): mp 184.4–187.0 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.87 (s, 1H), 7.51–7.47 (m, 2H), 7.45 (dd, J = 3.0 and 1.3 Hz, 1H), 7.32 (m, 2H), 7.22–7.14 (m, 7H), 7.12 (dd, J = 5.1 and 3.0 Hz, 1H), 7.05–6.94 (m, 4H), 2.24 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 197.0 (CO), 152.4 (CH), 150.0 (C), 149.7 (C), 140.2 (C), 139.1 (C), 137.4 (C), 135.8 (C), 133.6 (CH), 133.0 (C), 131.5 (CH), 129.6 (CH), 129.4 (CH), 129.2 (CH), 128.6 (CH), 128.49 (CH), 128.45 (CH), 127.9 (CH), 126.9 (CH), 125.8 (CH), 119.6 (C), 118.8 (C), 96.9 (C), 85.0 (C), 21.7 (CH₃); IR (neat): 3055, 3024, 2213, 1670, 1594, 1556, 1524, 1507, 1495, 1441, 1327, 1286, 1260, 1224, 1174, 1155, 1121, 1103, 1077, 1001, 1077, 1001, 908, 868, 816, 791, 764, 702, 686, 670, 617, 579, 530 cm⁻¹; MS (ESI, m/z): 456.14 [M + H]⁺; HRMS (ESI): calcd for C₃₁H₂₂NOS: 456.1417 [M + H]⁺, found: 456.1438.

Phenyl(4-phenyl-2-(thiophen-3-yl)-5-(thiophen-3-ylethynyl)pyridin-3-yl)methanone (7w). (5-Iodo-4-phenyl-2-(thiophen-3-yl)pyridin-3-yl)(phenyl)methanone (4c) (93.5 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and 3-ethynylthiophene (6l) (32.4 mg, 0.30 mmol) were employed to afford 65.3 mg (73%) of the indicated product as a brown solid (R_f = 0.35 in 4 : 1 hexane/ethyl acetate): mp 189.0–192.2 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.86 (s, 1H), 7.51–7.46 (m, 2H), 7.45 (dd, J = 2.9, 1.2 Hz, 1H), 7.35–7.28 (m, 2H), 7.22–7.10 (m, 10H), 6.81 (dd, J = 5.0 and 1.1 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 196.9 (CO), 152.3 (CH), 150.1 (C), 149.8 (C), 140.2 (C), 137.4 (C), 135.8 (C), 133.6 (CH), 133.0 (C), 129.7 (CH), 129.6 (CH), 129.4 (2 × CH), 128.6 (CH), 128.51 (CH), 128.45 (CH), 127.9 (CH), 127.0 (CH), 125.8 (CH), 125.6 (CH), 121.8 (C), 118.7 (C), 91.9 (C), 85.2 (C); IR (neat): 3093, 3080, 2209, 1732, 1666, 1593, 1558, 1517, 1493, 1443, 1342, 1313, 1299, 1226, 1207, 1174, 1078, 1007, 930, 881, 850, 791, 778, 761, 717, 702, 676, 641, 612, 566 cm⁻¹; MS (ESI, m/z): 448.08 [M + H]⁺; HRMS (ESI): calcd for C₂₈H₁₈NOS₂: 448.0824 [M + H]⁺, found: 448.0848.

Phenyl(4-phenyl-5-(ferrocenylethynyl)-2-(thiophen-3-yl)pyridin-3-yl)methanone (7x). (5-Iodo-4-phenyl-2-(thiophen-3-yl)pyridin-3-yl)(phenyl)methanone (4c) (93.5 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and ethynylferrocene (6o) (63.0 mg, 0.30 mmol) were employed to afford 87.9 mg (80%) of the indicated product as a red solid (R_f = 0.50 in 4 : 1 hexane/ethyl acetate): mp 176.8–178.5 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.86 (s, 1H), 7.53 (dd, J = 8.3 and 1.1 Hz, 2H), 7.50 (dd, J = 2.9 and 1.3 Hz, 1H), 7.41–7.35 (m, 2H), 7.29–7.20 (m, 7H), 7.16 (dd, J = 5.1 and 3.0 Hz, 1H), 4.21 (t, J = 1.8 Hz, 2H), 4.12 (t, J = 1.8 Hz, 2H), 3.95 (s, 5H); ¹³C NMR (100 MHz, CDCl₃) δ 196.6 (CO), 152.3 (CH), 149.7 (C), 149.2 (C), 140.5 (C), 137.6 (C), 136.3 (C), 133.5 (CH), 133.0 (C), 129.7 (CH), 129.4 (CH), 128.7 (CH), 128.6 (CH), 128.4 (CH), 128.0 (CH), 126.8 (CH), 125.6 (CH), 119.3 (C), 96.4 (C) 81.9 (C), 71.5 (CH), 70.2 (CH), 69.2 (CH), 64.4 (C); IR (neat): 3107, 3089, 2212, 1734, 1667, 1594, 1578, 1559, 1524, 1474, 1447, 1435, 1412, 1344, 1315, 1218, 1175, 1160, 1104, 1043, 1024, 1001, 911, 881, 850, 831, 808, 780, 721, 699, 679, 610, 576, 534, 494, 483, 466 cm⁻¹; MS (ESI, m/z): 548.10 [M + H]⁺; HRMS (ESI): calcd for C₃₄H₂₄⁵⁴FeNOS: 548.0969 [M + H]⁺, found: 548.1042.

(4-(3-Bromophenyl)-2-phenyl-5-(phenylethynyl)pyridin-3-yl)(phenyl)methanone (7y). (4-(3-Bromophenyl)-5-iodo-2-phenylpyridin-3-yl)(phenyl)methanone (4d) (108.0 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and phenylacetylene (6a) (30.6 mg, 0.30 mmol) were employed to afford 82.3 mg (84%) of the indicated product as an orangish yellow solid (R_f = 0.45 in 4 : 1 hexane/ethyl acetate): mp 168.0–171.0 °C. ¹H NMR (400 MHz, CDCl₃) δ 9.05 (s, 1H), 7.60–7.51 (m, 5H), 7.42 (ddd, J = 5.3, 3.3 and 1.3 Hz, 2H), 7.36–7.30 (m, 5H), 7.28 (dt, J = 10.9 and 4.7 Hz, 5H), 7.20 (br s, 1H), 7.17–7.12 (m, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 196.2 (CO), 155.6 (C), 152.7 (CH), 148.6 (C), 139.0 (C), 137.9 (C), 137.5 (C), 133.7 (CH), 133.6 (CH), 132.7 (C), 131.8 (CH), 131.7 (CH), 129.6 (CH), 129.4 (CH), 129.3 (CH), 129.1 (CH), 129.1 (CH), 128.6 (CH), 128.54 (2 × CH), 128.48 (CH), 122.4 (C), 121.9 (C), 118.8 (C), 97.3 (C), 85.0 (C); IR (neat): 3057, 3027, 2217, 2201, 1731, 1665, 1595, 1552, 1490, 1477, 1437, 1324, 1285, 1257, 1222, 1176, 1072, 1004, 994, 875, 785, 754, 726, 689, 526 cm⁻¹; MS (ESI, m/z): 514.08 [M + H]⁺; HRMS (ESI): calcd for C₃₂H₂₁⁷⁹BrNO: 514.0801 [M + H]⁺, found: 514.0817.

(4-Methyl-2-phenyl-5-(phenylethynyl)pyridin-3-yl)(phenyl)methanone (7z). (5-Iodo-4-methyl-2-phenylpyridin-3-yl)(phenyl)methanone (4e) (79.8 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and phenylacetylene (6a) (30.6 mg, 0.30 mmol) were employed to afford 63.5 mg (85%) of the indicated product as an light yellow solid (R_f = 0.50 in 4 : 1 hexane/ethyl acetate): mp 104.0–107.1 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.81 (s, 1H), 7.55 (dd, J = 5.2 and 3.3 Hz, 2H), 7.50 (dt, J = 5.0 and 3.0 Hz, 2H), 7.44–7.35 (m, 3H), 7.31 (dd, J = 5.9 and 2.6 Hz, 3H), 7.23 (t, J = 7.8 Hz, 2H), 7.18–7.11 (m, 3H), 2.35 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 197.5 (CO), 154.8 (C), 152.3 (CH), 146.9 (C), 139.2 (C), 136.9 (C), 134.2 (C), 133.9 (CH), 131.8 (CH), 129.5 (CH), 129.2 (CH), 129.1 (CH), 128.9 (CH), 128.8 (CH), 128.6 (CH), 128.4 (CH), 122.7 (C), 119.9 (C), 97.5 (C), 84.8 (C), 18.1 (CH₃); IR (neat): 3049, 2923, 2851, 1993, 1595, 1529, 1487, 1438, 1375, 1319, 1285, 1247, 1207, 1175, 1148, 1068, 1026, 999, 963, 938, 889, 844, 754, 712, 699, 687, 531 cm⁻¹; MS (ESI, m/z): 374.16 [M + H]⁺; HRMS (ESI): calcd for C₂₇H₂₀NO: 374.1539 [M + H]⁺, found: 374.1604.

(2-Butyl-4-phenyl-5-(phenylethynyl)pyridin-3-yl)(phenyl)methanone (7aa). (2-Butyl-5-iodo-4-phenylpyridin-3-yl)(phenyl)methanone (4f) (88.3 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and phenylacetylene (6a) (30.6 mg, 0.30 mmol) were employed to afford 71.5 mg (86%) of the indicated product as an orangish yellow solid (R_f = 0.57 in 4 : 1 hexane/ethyl acetate): mp 86.2–89.1 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.80 (s, 1H), 7.49 (dd, J = 5.2 and 3.3 Hz, 2H), 7.36 (tt, J = 7.1 and 1.2 Hz, 1H), 7.24–7.10 (m, 12H), 2.61 (t, J = 7.8 Hz, 2H), 1.61 (br s, 2H), 1.22 (sextet, J = 7.2 Hz, 2H), 0.75 (t, J = 7.3 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 197.0 (CO), 158.4 (C), 152.5 (CH), 149.0 (C), 137.3 (C), 135.9 (C), 133.9 (C), 133.7 (CH), 131.5 (CH), 129.7 (CH), 129.4 (CH), 128.7 (CH), 128.5 (2 × CH), 128.4 (CH), 127.8 (CH), 122.8 (C), 117.5 (C), 95.5 (C), 85.6 (C), 36.2 (CH₂), 31.9 (CH₂), 22.8 (CH₂), 13.9 (CH₃); IR (neat): 3052, 2954, 2928, 2865, 1735, 1665, 1596, 1579, 1560, 1525, 1490, 1447, 1421, 1326, 1281, 1266, 1223, 1154, 1071, 1002, 992, 916, 882, 754, 717, 701, 688, 669, 522 cm⁻¹; MS (ESI, m/z): 416.20 [M + H]⁺; HRMS (ESI): calcd for C₃₀H₂₆NO: 416.2009 [M + H]⁺, found: 416.2032.

1-(2,4-Diphenyl-5-(phenylethynyl)pyridin-3-yl)ethanone (7ab). 1-(5-Iodo-2,4-diphenylpyridin-3-yl)ethanone (4g) (79.8 mg, 0.20 mmol), PdCl₂(PPh₃)₂ (7.0 mg, 0.01 mmol), CuI (1.9 mg, 0.01 mmol) and phenylacetylene (6a) (30.6 mg, 0.30 mmol) were employed to afford 68.0 mg (91%) of the indicated product as a yellow solid (R_f = 0.53 in 4 : 1 hexane/ethyl acetate): mp 129.8–132.5 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.84 (s, 1H), 7.54–7.50 (m, 2H), 7.41–7.34 (m, 6H), 7.34–7.30 (m, 2H), 7.22–7.15 (m, 3H), 7.13 (dt, J = 8.0 and 2.1 Hz, 2H), 1.84 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 203.9 (CO), 154.0 (C), 152.0 (CH), 148.8 (C), 139.1 (C), 136.6 (C), 136.1 (C), 131.6 (CH), 129.4 (CH), 129.3 (CH), 129.1 (CH), 128.88 (CH), 128.75 (CH), 128.4 (CH), 128.3 (2 × CH), 122.6 (C), 119.1 (C), 96.7 (C), 85.4 (C), 32.7 (CH₃); IR (neat): 3054, 2208, 1960, 1897, 1703, 1554, 1518, 1487, 1440, 1411, 1375, 1348, 1325, 1309, 1196, 1178, 1101, 1073, 1025, 974, 919, 910, 754, 701, 690, 668, 651, 511 cm⁻¹; MS (ESI, m/z): 374.15 [M + H]⁺; HRMS (ESI): calcd for C₂₇H₂₀NO: 374.1539 [M + H]⁺, found: 374.1543.

2-Methoxy-3-(phenylethynyl)pyridine (9). 3-Iodo-2-methoxypyridine (8a) (70.5 mg, 0.30 mmol), PdCl₂(PPh₃)₂ (10.5 mg, 0.015 mmol), CuI (2.9 mg, 0.015 mmol) and phenylacetylene (6a) (45.9 mg, 0.45 mmol) were employed to afford 56.5 mg (90%) of the indicated product as a light yellow oil (R_f = 0.50 in 4 : 1 hexane/ethyl acetate). ¹H NMR (400 MHz, CDCl₃) δ 8.13 (dd, J = 5.0 and 1.9 Hz, 1H), 7.75 (dd, J = 7.4 and 1.9 Hz, 1H), 7.60–7.53 (m, 2H), 7.37–7.31 (m, 3H), 6.87 (dd, J = 7.4 and 5.0 Hz, 1H), 4.04 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 163.7 (CO), 146.4 (CH), 141.7 (CH), 131.8 (CH), 128.6 (CH), 128.4 (CH), 123.2 (C), 116.5 (CH), 107.6 (C), 94.7 (C), 84.2 (C), 54.1 (CH₃); IR (neat): 2949, 1571, 1491, 1464, 1400, 1300, 1261, 1230, 1144, 1100, 1069, 1014, 915, 867, 795, 755, 690, 569, 539 cm⁻¹; MS (ESI, m/z): 210.09 [M + H]⁺; HRMS (ESI): calcd for C₁₄H₁₂NO: 210.0919 [M + H]⁺, found: 210.0919.

3-Iodo-2-(phenylethynyl)pyridine (10), 2-iodo-3-(phenylethynyl)pyridine (11) and 2,3-bis(phenylethynyl)pyridine (12). As a representative example, the reaction in entry 3 of Table 3 was given. 2,3-Diiodopyridine (8b) (99.3 mg, 0.30 mmol), PdCl₂(PPh₃)₂ (10.5 mg, 0.015 mmol), CuI (2.9 mg, 0.015 mmol) and phenylacetylene (6a) (45.9 mg, 0.45 mmol) were employed to afford three fractions. First fraction (R_f = 0.40 in 4 : 1 hexane/ethyl acetate) produced 8.2 mg (9%) of alkynylpyridine 11 as a yellow solid: mp 66.5–69.2 °C. Second fraction (R_f = 0.30 in 4 : 1 hexane/ethyl acetate) yielded 31.1 mg (34%) of alkynylpyridine 10 as a light yellow oil. Third fraction (R_f = 0.23 in 4 : 1 hexane/ethyl acetate) provided 26.8 mg (32%) of dialkynylpyridine 12 as a brownish oil.
10. ¹H NMR (400 MHz, CDCl₃) δ 8.57 (dd, J = 4.7 and 1.5 Hz, 1H), 8.15 (dd, J = 8.1 and 1.5 Hz, 1H), 7.72–7.61 (m, 2H), 7.46–7.34 (m, 3H), 6.96 (dd, J = 8.0 and 4.7 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 148.9 (CH), 147.5 (C), 146.2 (CH), 132.3 (CH), 129.5 (CH), 128.6 (CH), 123.6 (CH), 122.0 (C), 98.9 (C), 93.4 (C), 90.4 (C); IR (neat): 3035, 2219, 2173, 1557, 1489, 1414, 1206, 1158, 1120, 1058, 1006, 916, 790, 755, 689, 563, 547, 521 cm⁻¹. The spectral data are in agreement with those reported previously for this compound.³⁹
11. ¹H NMR (400 MHz, CDCl₃) δ 8.28 (d, J = 3.1 Hz, 1H), 7.70 (dd, J = 7.7 and 1.8 Hz, 1H), 7.64–7.59 (m, 2H), 7.43–7.37 (m, 3H), 7.26 (dd, J = 7.5 and 4.9 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 148.9 (CH), 139.1 (CH), 131.9 (C), 131.8 (CH), 129.4 (CH), 129.0 (C), 128.7 (CH), 124.3 (C), 122.4 (CH), 96.3 (C), 89.2 (C); IR (neat): 2919, 2215, 1594, 1561, 1538, 1488, 1440, 1378, 1312, 1152, 1113, 1070, 1055, 1044, 801, 757, 723, 690, 641, 547 cm⁻¹; MS (ESI, m/z): 305.98 [M + H]⁺; HRMS (ESI): calcd for C₁₃H₉NI: 305.9780 [M + H]⁺, found: 305.9779.
12. ¹H NMR (400 MHz, CDCl₃) δ 8.54 (dd, J = 4.8 and 1.7 Hz, 1H), 7.83 (dd, J = 7.9 and 1.7 Hz, 1H), 7.66–7.61 (m, 2H), 7.60–7.55 (m, 2H), 7.40–7.32 (m, 6H), 7.21 (dd, J = 7.9 and 4.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 148.8 (CH), 145.1 (C), 138.9 (CH), 132.2 (CH), 131.8 (CH), 129.2 (CH), 129.0 (CH), 128.6 (CH), 128.5 (CH), 123.1 (C), 122.7 (C), 122.4 (C), 122.1 (CH), 96.2 (C), 93.5 (C), 88.0 (C), 86.0 (C); IR (neat): 3052, 2217, 1733, 1596, 1571, 1546, 1490, 1441, 1419, 1234, 1157, 1090, 915, 800, 755, 689, 533 cm⁻¹. The spectral data are in agreement with those reported previously for this compound.⁴⁰

Acknowledgements

We thank the Scientific and Technological Research Council of Turkey (TUBITAK, Grant No. 110T113) and the Research Fund of Middle East Technical University (METU, Grant No. BAP-2011-07-02-00-01) for financial support of this research.

Notes and references

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Footnotes

† Dedicated to Prof. Dr Metin Balci on the occasion of his retirement.

‡ Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra21701f

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