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Article

The Regio- and Stereoselective Synthesis of 1,4-Diarylbut-1-en-3-ynes Having Aryl Groups at the Mutual Syn Positions

by
Szymon Rogalski
,
Natalia Szymaszek
and
Cezary Pietraszuk
*
Faculty of Chemistry, Adam Mickiewicz University, Poznań, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland
*
Author to whom correspondence should be addressed.
Organics 2023, 4(2), 206-218; https://doi.org/10.3390/org4020017
Submission received: 2 February 2023 / Revised: 22 April 2023 / Accepted: 25 April 2023 / Published: 8 May 2023
Browse Figures
Versions Notes

Abstract

:
(E)-1-aryl-2,4-bis(trimethylsilyl)but-1-en-3-ynes readily undergo protodesilylation and subsequent aerobic, copper-free Sonogashira cross-coupling with aryl halides to form (E)-1,4-diaryl-2-(trimethylsilyl)but-1-en-3-ynes. The proposed one-pot, two-step approach allows access to the isomers containing aryl substituents in mutual syn positions. The resulting 2-silyl enynes can be further converted by proto- or halodesilylation.

Graphical Abstract

1. Introduction

Conjugated enynes are valuable moieties in organic chemistry, providing convenient starting materials for constructing aromatic and heteroaromatic molecules [1,2,3,4,5,6]. Their structural motif is present in numerous biologically active molecules [7,8,9,10] and some functional materials [11,12]. A general method for the synthesis of enynes must ensure the regio- and stereoselective formation of the target compounds. The substitution pattern and stereoelectronic properties of the substituents significantly influence the reactivity, making a single and general synthetic route difficult to achieve. State-of-the-art catalytic methods for the synthesis of conjugated enynes have been reported in several reviews [9,13,14] and there has been significant progress in recent years. Several new examples of the synthesis and reactivity of conjugated enynes have been described [14]. The number of applications of conjugated enynes in the synthesis of organic compounds is steadily increasing [2,3,4,15,16].
The selective synthesis of 1,4-diarylbut-1-ene-3-ynes with the same substituents in positions 1 and 4 can be conveniently performed via selective alkyne homo-dimerization. However, if the substituents at positions 1 and 4 are different (Figure 1a), alkyne cross-dimerisation may not always be applicable due to low selectivity. In this case, other procedures may need to be applied (Scheme 1).
If the synthesis target involves 1,4-diaryl-1,3-enynes that have aryl groups placed in mutual syn positions (Figure 1b), cross-coupling [17,18,19,26,36,37,38] is the only suitable synthetic route. Given the availability of procedures for the selective synthesis of silylated enynes (Figure 1c), the most convenient method for the preparation of (Z)-1,4-diaryl-1,3-enynes is the protodesilylation of the silyl derivatives followed by Sonogashira coupling with aryl halides [39,40,41,42,43,44]. Alternatively, a one-step sila-Sonogashira coupling of the silylated enynes with aryl halides (E in Scheme 1) can be used [45]. These reports are listed in Table S1 in the Supplementary Materials. However, such a sequence of reactions has not been developed into a general method for the synthesis of conjugated enynes with defined stereochemistry. To address this limitation, we report an efficient and general procedure for the synthesis of (E)-1,4-diaryl-2-(trimethylsilyl)but-1-en-3-ynes via the one-pot sequence of selective protodesilylation and Sonogashira coupling (Scheme 2).
In addition, we describe preliminary studies on using the reactivity of the silyl group in position 2 for the modification of the synthesised enynes.

2. Results and Discussion

First, three bissilylated 1,3-enynes with different aryl groups (Scheme 3) were selected for the optimisation of the protodesilylation procedure. For the reaction starting conditions, we adopted the previously developed procedure for the protodesilylation of (E)-4-aryl-1,3-bis(trimethylsilyl)but-3-en-1-yne [46].
We started the study by treatment of a methanolic solution of bissilylated 1,3-enyne 1a with an excess (5 equivalents) of KF. The reaction was carried out in air at 65 °C and led to the formation of the new compound in good yield after 3 h. GC-MS and NMR analyses showed the exclusive formation of the product 2a, selectively desilylated at the acetylene moiety.
The protodesilylation procedure has been adapted for convenient use application in a one-pot sequence. The optimization research included the selection of the solvent, the base, and the reaction conditions.
Of the bases tested, TBAF, KOt-Bu, and KOH resulted in the decomposition of 1a and the formation of a mixture of unidentified compounds. In contrast, the reaction with KF, CsF, NaF, and K2CO3 in the MeOH solution was efficient even at room temperature. Raising the temperature to 65 °C reduced the reaction time required for complete conversion from 3 h to 1 h. Under these conditions, the silyl group at the Csp2 carbon atom remained untouched. Solvents commonly used for Sonogashira connections, such as THF, DMF, and toluene, resulted in reduced conversion and yield. The results are summarised in Table 1.
After establishing the protodesilylation conditions, we investigated the Sonogashira coupling of terminal enyne with aryl bromides (or iodides) to find a convenient and efficient procedure. To find the optimum catalyst, base, and reaction conditions, studies were carried out using the cross-coupling of (E)-1-(4-methoxyphenyl)-2-trimethylsilylbut-1-en-3-yne (2a) with iodobenzene (Scheme 4) as a test reaction.
A series of commercially available palladium complexes such as [PdCl2(PPh3)2], [Pd2(dba)3]/PPh3, [Pd(PPh3)4], PdCl2/dppf (dppf = 1,1′-bis(diphenylphosphino)ferrocene), [PdCl2(PhCN)2]/PPh3, and PEPPSI-IPr ([1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridine)palladium(II) dichloride) were evaluated (Table 2). The greatest yields were observed for the phosphine-based catalysts [Pd(PPh3)4] and [PdCl2(PPh3)2]. The other palladium complexes exhibited lower activity. Among the bases tested, KF and NEt3 gave the best performance. Finally, the high yields of Sonogashira cross-coupling under copper-free conditions prompted us to investigate the effect of the copper salt on the course of the reaction. Regardless of the amount of CuI used (1, 2, or 5 equivalents in relation to the catalyst), the course of the reaction was unaffected.
Next, reactions were carried out in the air, using commercially available solvents and reagents without further purification. Performing the reaction in MeOH at 65 °C in the presence of [PdCl2(PPh3)2] (1 mol%) and NEt3 proved to be optimal. Under these conditions, product yields of up to 99% were obtained at a relatively low reaction temperature (65 °C) and catalyst loading (1 mol%). Following the optimisation studies, the one-pot syntheses of the 1,4-diarylbut-1-en-3-ynes were assessed according to Scheme 5.
The silylated 1,3-enynes were found to undergo efficient protodesilylation/Sonogashira coupling with a wide range of aromatic bromides and iodides (Figure 2). Products 4a–o were obtained by treating, in the first step, a methanolic solution of bissilylated 1,3-enynes (1a–e) with 5 equivalents of K2CO3 at 65 °C. The reaction was carried out for 1 h and the progress was monitored by GC-MS. After completion of the protodesilylation, the corresponding aromatic bromide or iodide was added together with NEt3 and palladium catalyst [PdCl2(PPh3)2] (1 mol%) and the reaction was continued for a further 23 h. It was possible to obtain 1,3-enynes with overall isolated yields in the range of 60% to 92% (Figure 2).
Isomers with aryl groups in mutual syn positions were selectively formed. This method allows for the efficient conversion of reagents containing amine, nitro, methyl, methoxy, trifluoromethyl, and thiophenyl groups. Aryl halides containing conjugated aromatic rings, such as naphthyl and phenanthryl, were efficiently converted. Meta-substituted phenyl halides were also proved to be suitable reagents (see products 4d and 4e, Figure 2).
The reported method is not free from limitations. Reagents containing aldehyde, nitrile, and hydroxide groups could not be efficiently converted under the conditions used and generated products with yields below 15%. Furthermore, ortho-nitro and ortho-methyl substituted phenylacetylenes did not undergo Sonogashira cross-coupling with protodesilylated 1a and trace amounts of the products were obtained. Nearly no conversion of aryl halides was observed. Other limitations relate to the optimisation of the one-pot process. For instance, THF and DMF are not suitable solvents in the proposed method.
Moreover, the reactivity of the silyl group attached to the enyne double bond allows further transformations. Treatment of 4l with KOt-Bu or KOH resulted in a mixture of unidentified products, and using KF as a desilylation agent had no effect. In contrast, desilylation with TBAF in CH2Cl2 solution at room temperature yielded 89% of the protodesilylated product (5) (Scheme 6).
The method described by Pawluć and Marciniec [47] was adapted for the iododesilylation of 4a. Halodesilylation of 1,3-enyne with N-iodosuccinimide (NIS) at room temperature did not lead to the formation of 6. Treatment of an acetonitrile solution of (E)-1-(4-methoxyphenyl)-2-(trimethylsilyl)-4-(phenyl)but-1-en-3-yne (4a) with NIS at 65 °C for 5 h afforded the compound 6 in 93% yield (Scheme 7). We only found one paper in the literature describing a similar iododesilylation at position 2 of conjugated enyne [48].

3. Conclusions

1,4-diaryl-2-(trimethylsilyl)but-1-en-3-ynes with aryl groups in mutual syn positions can be obtained selectively by the one-pot sequence of protodesilylation of (E)-1-aryl-2,4-bis(trimethylsilyl)but-1-en-3-ynes followed by the aerobic, copper-free Sonogashira cross-coupling of terminal enynes with aryl halides. This method allows for the synthesis of a wide range of 1,4-diaryl-2-silyl-1,3-enynes in moderate to high yields. The synthesised enynes can undergo proto- and halodesilylation, yielding useful building blocks.

4. Experimental

General methods and chemicals. All activities were conducted in the air. 1H and 13C NMR spectra were recorded using a Varian 400 instrument at 402.6 and 101.2 MHz, respectively. All spectra were recorded at 298 K. GC analyses were performed using a Bruker Scion 436-GC (column: DB-5 30 m I.D. 0.53 mm) equipped with a TCD. GC/MS analyses were performed using a Varian Saturn 2100T instrument equipped with (DB-1, 30 m capillary column, 0.25 mm I.D.) and an ion trap detector. IR spectra were recorded on Jasco FT/IR-4600 spectrometer. HRMS analyses were performed using a QTOF mass spectrometer (Impact HD, Bruker Daltonics). Chemicals: KF, all aryl bromides, iodides, PdCl2, PPh3, methanol (99.6%), tetrahydrofuran, and K2CO3 were purchased from Merck. The complexes [Pd(PPh3)4], [PdCl2(PPh3)2], and [PdCl2(PhCN)2] were synthesised according to the published procedures [49,50].
Optimisation of protodesilylation. A 10 mL two-neck round bottom flask, equipped with a magnetic stirring bar, was charged with 0.069 g (0.225 mmol) of representative (E)-1-(4-methoxyphenyl)-2,4-bis(trimethylsilyl)but-1-en-3-yne, 5 mL of MeOH, 0.2 g of K2CO3, and 0.03 mL of dodecane (internal standard). The vial was closed under air and then stirred and heated at temperatures ranging from 25 to 65 °C in an oil bath for a given reaction time. The reaction course was monitored by gas chromatography.
Optimisation of Sonogashira coupling. First, 25 µL (0.225 mmol) of iodobenzene, 0.15 mL of NEt3, and 0.0045 mmol of Pd catalyst were added to the methanol solution of desilylated 1,3-enyne. The reaction mixture was heated at various temperatures ranging from 25 to 65 °C in an oil bath for a given reaction time. The reaction course was monitored by gas chromatography.
Representative one-pot synthesis. The synthesis was carried out in a two-neck round bottom flask with a capacity of 100 mL and equipped with a magnetic stirring bar under a closed system. The flask was charged with 0.25 g (0.817 mmol) of (E)-1-(4-methoxyphenyl)-2,4-bis(trimethylsilyl)but-1-en-3-yne, 20 mL of MeOH, and 0.58 g of K2CO3 (4.09 mmol). The reaction mixture was stirred and heated at 65 °C in an oil bath for 1 h. Afterwards, 0.9 mL (0.817 mmol) of iodobenzene, 0.5 mL of NEt3, and 0.006 g (0.0817 mmol) of [PdCl2(PPh3)2] were added to the reaction mixture, and the heating was continued for an additional 23 h. Then, the solvent was removed under vacuum, and the solid residue was purified by column chromatography over silica gel and using hexane/ethyl acetate (25:1) as an eluent. Products characterisation
4a. Isolated as a yellow oil, 225 mg (92% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 7.99 (d, J = 8.5 Hz, 2H, C6H4), 7.50–7.47 (m, 2H, Ph), 7.31–7.35 (m, 3H, Ph), 6.91 (d, J = 8.9 Hz, 2H, C6H4), 6.80 (s, 1H, =CH), 3.84 (s, 3H, OMe), 0.29 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 159.67, 143.46, 132.35, 131.24, 130.59, 130.30, 128.33, 127.80, 124.50, 113.74, 113.57, 90.59, 55.28, −1.79; IR (νmax, cm−1): 3065, 2954, 2838, 2553, 1684, 1599, 1509, 1447, 1422, 1248, 1170, 1109, 1025, 835, 757, 693, 610, 546; GC-MS (EI): m/z (rel intensity): 45 (10), 59 (10), 73 (50), 292 (38), 306 (100, M+); HRMS (ESI+): calc for [C20H22OSi + H]+: 307.1513; found: 307.1512.
4b. Isolated as a yellow oil, 155 mg (60% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 7.99–7.97 (m, 2H, C6H4), 7.34 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 6.83 (broad, J = 8.7 Hz, 2H), 6.74 (s, 1H, =CH), 5.08 (brs, 2H, -NH2, 3.83 (s, 3H, OMe), 0.27 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 159.51, 142.47, 132.64, 132.16, 131.11, 130.16, 124.80, 120.62, 116.59, 113.59, 100.63, 89.48, 55.27, −2.04. IR (νmax, cm−1): 3459, 3369, 2953, 2836, 2548, 2166, 1890, 1599, 1504, 1457, 1403, 1303, 1244, 1171, 1112, 1025, 826, 756, 690, 589, 526; GC-MS (EI): m/z (rel intensity): 73 (11), 306 (30), 307 (10), 321 (100, M+); HRMS (ESI+): calc for [C20H23NOSi + H]+: 322.1622; found: 322.1616.
4c. Isolated as a yellow-orange solid, 235 mg (72% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 8.72–8.65 (m, 2H, Ar), 8.55–8.53 (m, 1H, Ar), 8.11–8.09 (m, 2H, C6H4), 8.00 (s, 1H, Ar), 7.91–7.87 (m, 2H, Ar), 7.73–7.59 (m, 3H, Ar), 6.95–6.93 (m, 2H, C6H4), 6.92 (s, 1H, =CH), 3.84 (s, 3H, OMe), 0.38 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 159.82, 151.68, 143.97, 131.29, 130.42, 130.01, 128.47, 127.22, 127.19, 126.97, 126.94, 126.92, 126.89, 126.54, 122.76, 122.61, 113.67, 98.40, 95.09, 55.31, −1.56. IR (νmax, cm−1): 3059, 2954, 2838, 2648, 2170, 1683, 1600, 1506, 1447, 1420, 1292, 1247, 1171, 1103, 1029, 834, 745, 724, 616, 510 GC-MS (EI): m/z (rel intensity): 406 (100, M+); HRMS (ESI+): calc for [C28H26OSi + H]+: 407.1826; found: 407.1814.
4d. Isolated as a yellow powder, 242 mg (86% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 8.28 (m, 1H, Ar), 8.16–8.14 (m, 1H, Ar), 7.93 (d, J = 8.6 Hz, 2H, C6H4), 7.74 (dt, J = 7.6, 1.4 Hz, 1H, Ar), 7.53–7.49 (m, 1H, Ar), 6.93 (d, J = 8.6 Hz, 2H, C6H4), 6.88 (s, 1H, =CH), 3.84 (s, 3H, OMe), 0.29 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 160.07, 145.43, 136.89, 133.31, 130.35, 129.27, 126.28, 125.82, 122.35, 113.81, 97.11, 93.40, 55.34, −1.57. IR (νmax, cm−1): 3060, 2951, 2831, 2183, 1657, 1590, 1515, 1402, 1331, 1250, 1179, 1101, 1008, 832, 750, 684, 630; GC-MS (EI): m/z (rel intensity): 73 (10), 262 (12), 336 (10), 351 (100, M+) HRMS (ESI+): calc for [C20H21NO3Si + Na]+: 374.1188; found: 374.1180.
4e. Isolated as a yellow oil, 222 mg (81% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 7.95 (d, J = 8.4 Hz, 2H, C6H4), 7.44–7.43 (m, 1H, Ar), 7.35–7.33 (m, 1H, Ar), 7.28–7.27 (m, 2H, Ar), 6.92 (d, J = 8.4 Hz, 2H, C6H4), 6.82 (s, 1H, =CH), 3.85 (s, 3H, OMe), 0.28 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 159.89, 144.37, 134.17, 130.97, 130.35, 129.51, 129.39, 127.99, 126.22, 119.83, 113.67, 104.38, 98.54, 91.89, 55.32, −1.77; IR (νmax, cm−1): 3032, 2911, 2883, 2143, 1662, 1618, 1599, 1565, 1372, 1334, 1258, 1149, 1191, 1108, 832, 721, 654, 629; GC-MS (EI): m/z (rel intensity): 73 (20), 202 (12), 251 (10), 326 (14), 340 (100, M+); HRMS (ESI+): calc for [C20H21ClOSi + Na]+: 363.0948; found: 363.1416.
4f. Isolated as a yellow oil, 163 mg (72% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 7.97 (d, J = 7.1 Hz, 2H, Ph), 7.40 (t, J = 7.7 Hz, 2H, Ph), 7.33–7.31 (m, 1H, Ph), 7.30 (dd, J = 5.1, 1.2 Hz, 1H), 7.22 (dd, J = 3.6, 1.3 Hz, 1H), 7.03 (dd, J = 5.2, 3.5 Hz, 1H), 6.86 (s, 1H, =CH), 0.32 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 13C NMR (101 MHz, cdcl3) δ 143.76, 137.66, 131.12, 128.66, 128.52, 128.27, 127.27, 127.18, 124.43, 123.10, 94.47, 94.02, −2.10. IR (νmax, cm−1): 3059, 2954, 2890, 2163, 1685, 1597, 1491, 1445, 1410, 1246, 1181, 1046, 990, 837, 753, 692, 631; GC-MS (EI): 45 (39), 73 (83), 75 (13), 141 (17), 164 (29), 171 (23), 182 (11), 191 (10), 280 (100), 281 (25), 282 (10, M+); HRMS (ESI+): calc for [C17H18SSi + H]+: 283.0971; found: 283.0976.
4g. Isolated as a yellow oil, 188 mg (68% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 7.99–7.96 (m, 2H, C6H4), 7.62–7.55 (m, 4H, Ph, C6H4), 7.42–7.30 (m, 3H, Ph), 6.93 (s, 1H, =CH), 0.31 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 147.02, 145.32, 137.46, 131.45, 130.22, 128.82, 128.78, 128.40, 128.34, 125.31 (q, J = 3.8 Hz) 123.03, 99.16, 92.75, −2.05. IR (νmax, cm−1): 3069, 2956, 2171, 1705, 1611, 1492, 1448, 1408, 1321, 1248, 1165, 1123, 1065, 1015, 834, 754, 692, 630, 593; GC-MS (EI): m/z (rel intensity): 251 (24), 252 (17), 323 (15), 325 (32), 326 (83), 327 (48), 343 (21), 344 (100, M+); HRMS (ESI+): calc for [C20H19F3Si + Na]+: 367.1100; found: 367.1115.
4h. Isolated as a dark yellow solid, 201 mg (78% yield). Spectroscopic characterization: 1H NMR (CDCl3; ppm) δ: 8.21 (d, J = 9.0 Hz, 2H, C6H4), 7.96–7.93 (m, 2H, Ph), 7.58 (d, J = 9.0 Hz, 2H, C6H4), 7.42–7.34 (m, 3H, Ph), 6.97 (s, 1H, =CH), 0.33 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 13C NMR (101 MHz, cdcl3) δ 153.48, 146.25, 137.38, 131.85, 131.20, 128.99, 128.83, 128.36, 128.07, 123.69, 98.42, 95.90, 29.68, −2.09. IR (νmax, cm−1): 3063, 2956, 2851, 2173, 1687, 1591, 1515, 1406, 1337, 1250, 1174, 1103, 1017, 834, 751, 689, 632; GC-MS (EI): m/z (rel intensity): 45 (37), 73 (100), 75 (17), 200 (28), 215 (14), 230 (22), 243 (18), 257 (13), 288 (20), 304 (22), 320 (38), 321 (10, M+); HRMS (ESI+): calc for [C19H19NO2Si + Na]+: 344.1077; found: 344.1090.
4i. Isolated as a yellow solid, 235 mg (90% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 8.43–8.41 (m, 1H, Ar), 8.11–8.09 (m, 2H, Ph), 7.88–7.80 (m, 2H, Ar), 7.71 (dd, J = 7.1, 1.2 Hz, 1H, Ar), 7.57–7.53 (m, 2H, Ar), 7.49–7.39 (m, 3H, Ph), 7.36–7.30 (m, 1H, Ar), 6.96 (s, 1H, =CH), 0.38 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 144.16, 137.80, 135.22, 134.99, 133.25, 133.07, 130.27, 128.80, 128.53, 128.49, 128.41, 128.29, 127.98, 126.65, 126.37, 125.37, 123.86, 99.02, 95.03, −1.67. IR (νmax, cm−1): 3363, 3055, 2954, 2165, 1686, 1636, 1590, 1505, 1445, 1398, 1246, 1173, 1107, 1022, 961, 835, 799, 772, 692, 630, 592; GC-MS (EI): m/z (rel intensity): 45 (27), 59 (13), 73 (79), 172 (14), 197 (13), 209 (15), 252 (37), 253 (24), 295 (13), 311 (16), 326 (100, M+); HRMS (ESI+): calc for [C23H22Si + H]+: 327.1564; found: 327.1552.
4j. Isolated as a yellow-orange solid, 235 mg (78% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 8.73–8.65 (m, 2H, Ar), 8.54–8.51 (m, 1H, Ar), 8.14–8.10 (m, 2H, Ph), 8.00 (s, 1H, Ar), 7.90–7.87 (m, 2H, Ar), 7.72–7.61 (m, 3H, Ar), 7.46–7.33 (m, 3H, Ph), 6.99 (s, 1H, =CH), 0.40 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 151.81, 144.43, 137.85, 131.51, 130.15, 128.84, 128.57, 128.51, 128.33, 127.30, 127.17, 127.00, 126.96, 126.93, 123.88, 122.75, 122.61, 120.85, 99.13, 94.68, −1.61. IR (νmax, cm−1): 3062, 2956, 2838, 2645, 2170, 1683, 1600, 1506, 1450, 1420, 1292, 1247, 1171, 1113, 1029, 834, 745, 725, 623; GC-MS (EI): m/z (rel intensity): 45 (19), 73 (50), 302 (23), 303 (19), 361 (11), 376 (100, M+); HRMS (ESI+): calc for [C27H24Si + H]+: 377.1720; found: 377.1712.
4k. Isolated as a yellow crystalline solid, 228 mg (78% yield). Purified by column chromatography over silica gel using n-hexane as an eluent, then recrystallized from n-hexane. Spectroscopic characterization: 1H NMR (CDCl3; ppm) δ: 8.04 (d, J = 7.9 Hz, 2H, Ph), 7.80–7.77 (m, 3H, Ar), 7.58–7.55 (m, 3H, Ph), 7.41–7.40 (m, 2H, Ar), 7.35–7.33 (m, 2H, Ar), 6.87 (s, 1H, =CH), 3.92 (s, 2H, -CH2-), 0.33 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 143.62, 141.12, 137.83, 131.56, 130.28, 128.74, 128.41, 128.35, 128.27, 127.84, 127.09, 126.90, 125.08, 123.78, 120.15, 119.79, 101.93, 90.41, 36.74, −1.77. IR (νmax, cm−1): 3056, 2954, 2206, 1711, 1685, 1603, 1489, 1451, 1400, 1247, 1180, 1101, 1023, 950, 916, 834, 750, 731, 689, 589; GC-MS (EI): m/z (rel intensity): 45 (10), 73 (11), 364 (100, M+); HRMS (ESI+): calc. for [C26H24Si + Na]+: 387.1539; found: 387.1544.
4l. Isolated as a yellow powder, 258 mg (88% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 7.94 (d, J = 8.0 Hz, 2H, C6H4), 7.63–7.59 (m, 4H, Ar), 7.56–7.55 (m, 2H, Ar), 7.48–7.45 (m, 2H, Ar), 7.39–7.36 (m, 1H, Ar), 7.22 (d, J = 8.0 Hz, 2H, C6H4), 6.86 (s, 1H, =CH), 2.39 (s, 3H, Me), 0.32 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 144.01, 140.61, 140.47, 138.55, 135.19, 131.69, 128.97, 128.85, 128.75, 127.55, 127.04, 126.98, 123.43, 122.19, 100.60, 91.31, 21.42, −1.98. IR (νmax, cm−1): 3046, 2930, 2850, 2505, 2140, 1688, 1525, 1480, 1413, 1332, 1250, 1181, 1116, 1054, 828, 750, 702, 568, 481; GC-MS (EI): m/z (rel intensity): 45 (10), 73 (12), 366 (100, M+) HRMS (ESI+): calc for [C26H26Si + Na]+: 389.1696; found: 389.1687.
4m. Isolated as a yellow powder, 230 mg (75% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 8.10 (d, J = 7.9 Hz, 2H, C6H4), 7.66–7.61 (m, 4H, C6H4, Ph), 7.37–7.35 (m, 1H, Ph), 6.90 (d, J = 7.9 Hz, 2H, C6H4), 6.87 (s, 1H, =CH), 3.84 (s, 3H, OMe), 0.31 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 159.48, 142.53, 140.68, 136.98, 132.77, 131.84, 129.12, 128.67, 127.43, 127.10, 126.83, 123.93, 116.60, 113.96, 101.57, 89.30, 55.32, −2.00; IR (νmax, cm−1): 3042, 2910, 2820, 2158, 1689, 1525, 1483, 1410, 1330, 1259, 1181, 1084, 822, 751, 698, 560, 496; GC-MS (EI): m/z (rel intensity): 73 (12), 368 (8), 382 (100, M+); HRMS (ESI+): calc for [C26H26OSi + Na]+: 405.1651; found: 405.1676.
4n. Isolated as a yellow oil, 195 mg (64% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 8.09 (d, J = 8.1 Hz, 2H, C6H4-CF3), 7.62 (d, J = 8.1 Hz, 2H, C6H4-CF3), 7.41 (d, J = 8.9 Hz, 2H C6H4-OMe), 6.90 (d, J = 8.9 Hz, 2H, C6H4-OMe), 6.83 (s, 1H, =CH), 3.84 (s, 3H, OMe), 0.31 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 159.79, 141.03, 141.00, 133.04, 132.89, 129.69, 128.65, 127.64, 125.08, 116.09, 114.14, 102.72, 88.62, 55.35, −1.89; IR (νmax, cm−1): 3039, 2942, 2131, 1675, 1601, 1462, 1408, 1329, 1242, 1165, 1119, 1034, 1022, 831, 772, 690, 630; GC-MS (EI): m/z (rel intensity): 73 (15), 267(10), 282 (10), 355 (16), 374 (100, M+); HRMS (ESI+): calc for [C21H21F3OSi + H]+: 375.1392; found: 375.1416.
4o. Isolated as a yellow oil, 202 mg (90% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 8.02 (d, J = 8.9 Hz, 2H, C6H4), 7.45 (d, J = 8.9 Hz, 2H, C6H4), 6.93, (d, J = 8.9 Hz, 2H, C6H4), 6.91 (d, J = 8.9 Hz, 2H, C6H4), 6.80 (s, 1H, =CH), 3.85 (s, 3H, OMe), 3.84 (s, 3H, OMe), 0.31 (s, 9H, SiMe3); 13C NMR (CDCl3; ppm) δ: 159.57, 159.34, 142.62, 132.64, 131.10, 130.18, 120.59, 116.72, 114.00, 113.52, 100.38, 89.35, 55.25, 55.22, −1.96; IR (νmax, cm−1): 3001, 2953, 2835, 2540, 2173, 2055, 1889, 1603, 1566, 1503, 1461, 1441, 1286, 1242, 1171, 1105, 1025, 864, 826, 754, 693, 614, 531; GC-MS (EI): m/z (rel intensity): 321 (10), 336 (100, M+); HRMS (ESI+): calc for [C21H24NaO2Si + Na]+: 359.1438; found: 359.1452.
Protodesilylation of 4l. A 10 mL two-neck round bottom flask, which was equipped with a magnetic stirring bar, was charged with 0.082 g (0.225 mmol) of (E)-1-(4-methylphenyl)-2-(trimethylsilyl)-4-biphenylbut-1-en-3-yne (4l), 5 mL of CH2Cl2, 0.18 g (0.675 mmol) of TBAF and 5 mL of CH2Cl2. The mixture was stirred at room temperature for 24 h. The solvent was then removed under vacuum, and the solid residue was purified by column chromatography on silica gel with hexane/ethyl acetate (25:1).
5. Isolated as a yellow oil, 59 mg (89% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 7.88 (d, 2H, J = 8.2 Hz, C6H4), 7.64–7.58 (m, 6H, Ar), 7.48–7.46 (m, 2H, Ar), 7.40–7.37 (m, 1H, Ar), 7.24 (d, 2H, J = 8.2 Hz, C6H4), 6.71 (d, 1H, J = 11.9 Hz, =CH), 5.91 (d, 1H, J = 11.9 Hz, =CH), 2.41 (s, 3H, -CH3); 13C NMR (CDCl3; ppm) δ: 140.97, 140.30, 138.66, 138.58, 133.89, 131.81, 129.00, 128.85, 128.73, 127.63, 127.06, 126.98, 122.46, 106.31, 95.55, 88.97, 21.39. IR (νmax, cm−1): 3028, 2921, 2853, 2182, 1913, 1677, 1602, 1512, 1485, 1448, 1403, 1321, 1259, 1180, 1112, 1078, 1036, 1006, 822, 761, 721, 692, 556, 499, 447; GC-MS (EI): m/z (rel intensity): 213 (2), 278 (5), 279 (7), 294 (100, M+); HRMS (ESI+): calc for [C23H18Si + Na]+: 317.1306; found: 317.1311.
Iododesilylation of 4a. A 10 mL two-neck round bottom flask, equipped with a magnetic stirring bar, was charged with 0.069 g (0.25 mmol) of (E)-1-(4-methoxyphenyl)-2-(trimethylsilyl)-4-phenylbut-1-en-3-yne (4a), 0.1 g (0.45 mmol) of NIS and 5 mL of MeCN. The mixture was stirred and heated in a closed system at 65 °C in an oil bath for 5 h. The solvent was removed under vacuum, and the solid residue was purified by column chromatography on silica gel with hexane/ethyl acetate (25:1).
6. Isolated as an orange-yellow oil, 83 mg (93% yield). Spectroscopic characterisation: 1H NMR (CDCl3; ppm) δ: 7.77–7.75 (m, 2H, C6H4), 7.50–7.49 (m, 2H, Ph), 7.38–7.37 (m, 3H, Ph), 7.34 (s, 1H, =CH), 6.88 (d, 2H, J = 9.0 Hz, C6H4), 3.83 (s, 3H, OMe); 13C NMR (CDCl3; ppm) δ: 160.08, 146.59, 131.49, 130.23, 129.85, 128.98, 128.39, 122.41, 113.82, 97.05, 91.10, 64.90, 55.31. IR (νmax, cm−1): 3001, 2929, 2837, 2167, 1883, 1717, 1685, 1598, 1507, 1443, 1293, 1254, 1175, 1026, 894, 823, 779, 755, 691, 631, 534; GC-MS (EI): m/z (rel intensity): 360 (100, M+); HRMS (ESI+): calc for [C17H13IO + H]+: 361.0089; found: 361.0069.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/org4020017/s1, Table S1: Literature reports on the application of silylenynes in the synthesis of 1,4-(diaryl)but-1-en-3-ynes substituted in positions 1 and 4 by different aryl groups, 1H and 13C, spectra of the products 4a-4o, 5 and 6.

Author Contributions

Conceptualization, S.R., N.S. and C.P.; methodology, C.P.; software, S.R. and N.S.; validation, C.P.; formal analysis, S.R. and N.S.; investigation S.R. and N.S.; resources, S.R. and N.S.; data curation, S.R., N.S. and C.P.; writing—original draft preparation, S.R., N.S. and C.P.; writing—review and editing, S.R., N.S. and C.P.; visualization, S.R. and N.S.; supervision, C.P.; project administration, C.P.; funding acquisition, S.R., N.S. and C.P. All authors have read and agreed to the published version of the manuscript.

Funding

The work was supported by grant no. POWR.03.02.00-00-I026/16 co-financed by the European Union through the European Social Fund under the Operational Program Knowledge Education Development.

Data Availability Statement

The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary Materials.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. The conjugated enyne substitution patterns that are addressed in this paper.
Figure 1. The conjugated enyne substitution patterns that are addressed in this paper.
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Scheme 1. General methods for the synthesis of conjugated 1,4-diarylenynes, where the substituents in the 1- and 4-positions are different. The available procedures include cross-coupling reactions, (i.e., Suzuki [17], Stille [18], Hiyama-Denmark [19], Sonogashira [20,21,22,23,24], Heck [25]) (A), Kumada [26], and Suzuki [27] (B), the hydroarylation of 1,3-diynes [28,29] (C), the hydroalkynylation of alkynes and/or allenes (D) [30,31], and a few less general procedures [32,33,34,35].
Scheme 1. General methods for the synthesis of conjugated 1,4-diarylenynes, where the substituents in the 1- and 4-positions are different. The available procedures include cross-coupling reactions, (i.e., Suzuki [17], Stille [18], Hiyama-Denmark [19], Sonogashira [20,21,22,23,24], Heck [25]) (A), Kumada [26], and Suzuki [27] (B), the hydroarylation of 1,3-diynes [28,29] (C), the hydroalkynylation of alkynes and/or allenes (D) [30,31], and a few less general procedures [32,33,34,35].
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Scheme 2. One-pot synthesis of 1,4-diarylbut-1-en-3-ynes.
Scheme 2. One-pot synthesis of 1,4-diarylbut-1-en-3-ynes.
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Scheme 3. Chemoselective protodesilylation of 2-silylsubstituted 1,3-enynes.
Scheme 3. Chemoselective protodesilylation of 2-silylsubstituted 1,3-enynes.
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Scheme 4. Sonogashira cross-coupling of 2a with iodobenzene.
Scheme 4. Sonogashira cross-coupling of 2a with iodobenzene.
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Scheme 5. The one-pot procedure of protodesilylation/Sonogashira coupling sequence.
Scheme 5. The one-pot procedure of protodesilylation/Sonogashira coupling sequence.
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Figure 2. Synthesised enynes (isolated yields are given).
Figure 2. Synthesised enynes (isolated yields are given).
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Scheme 6. Protodesilylation of 2-silylsubstituted 1,4-(diaryl)but-1-en-3-yne.
Scheme 6. Protodesilylation of 2-silylsubstituted 1,4-(diaryl)but-1-en-3-yne.
Organics 04 00017 sch006
Organics 04 00017 sch007 550
Scheme 7. Iododesilylation of 2-silylsubstituted 1,4-(diaryl)but-1-en-3-yne.
Scheme 7. Iododesilylation of 2-silylsubstituted 1,4-(diaryl)but-1-en-3-yne.
Organics 04 00017 sch007
Table
Table 1. Optimisation of the conditions for protodesilylation of 1a–c.
Table 1. Optimisation of the conditions for protodesilylation of 1a–c.
EnyneBaseTime [h]SolventConv.Yield [%]
1aKF 3toluene0 0
1aK2CO33toluene00
1aKF3DMF2722
1aKF 3THF 55
1aKF3MeOH 100 a99 a
1aCsF2.5MeOH10099
1aNaF3MeOH6565
1aK2CO3 3MeOH 100 a99 a
1aKF 1MeOH 10099
1aTBAF 1MeOH1005
1aKOt-Bu 3MeOH 10030
1aKOH3MeOH 10022
1aK2CO3 1MeOH 10099
1bK2CO3 1 MeOH 10098
1cK2CO3 1 MeOH 10096
Conditions: MeOH, base (5 equiv); 65 °C, a 25 °C.
Table
Table 2. Optimisation of Sonogashira cross-coupling of 2a with iodobenzene.
Table 2. Optimisation of Sonogashira cross-coupling of 2a with iodobenzene.
Cat. Additive
(Amount) a		BaseConv. [%]Yield [%]
[Pd(PPh3)4] -KF 10099
[Pd(PPh3)4]-NEt310098
[Pd(PPh3)4]CuI (see text)KF10098
[PdCl2(PPh3)2] -KF10098
[PdCl2(PPh3)2] -NEt310099
[PdCl2(PPh3)2] -NEt398 a98 a
[PdCl2(PPh3)2] CuI (see text)KF10098
[PdCl2(PPh3)2] -KF97 b96 b
[PdCl2(PPh3)2] -K2CO39090
PEPPSI-IPr -KF 9995
PEPPSI-IPr -NEt39994
[Pd2(dba)3]PPh3 (2 equiv)NEt39995
[Pd2(dba)3]SPhos (2 equiv)NEt310096
PdCl2dppf (1 equiv)KF7575
[PdCl2(PhCN)2]PPh3 (2 equiv)KF8786
Reaction conditions: MeOH, [Pd] (1 mol%), air, 3 h; 65 °C; a in relation to the catalyst; b 24 h, 25 °C.
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MDPI and ACS Style

Rogalski, S.; Szymaszek, N.; Pietraszuk, C. The Regio- and Stereoselective Synthesis of 1,4-Diarylbut-1-en-3-ynes Having Aryl Groups at the Mutual Syn Positions. Organics 2023, 4, 206-218. https://doi.org/10.3390/org4020017

AMA Style

Rogalski S, Szymaszek N, Pietraszuk C. The Regio- and Stereoselective Synthesis of 1,4-Diarylbut-1-en-3-ynes Having Aryl Groups at the Mutual Syn Positions. Organics. 2023; 4(2):206-218. https://doi.org/10.3390/org4020017

Chicago/Turabian Style

Rogalski, Szymon, Natalia Szymaszek, and Cezary Pietraszuk. 2023. "The Regio- and Stereoselective Synthesis of 1,4-Diarylbut-1-en-3-ynes Having Aryl Groups at the Mutual Syn Positions" Organics 4, no. 2: 206-218. https://doi.org/10.3390/org4020017

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