Pd/Cu-Catalyzed Cross-Coupling of Bis(2-bromovinyl) Selenides with Terminal Acetylenes: Unusual Involvement of Selanyl Function in the Sonogashira Reaction

Abstract

The Pd/Cu-catalyzed Sonogashira reaction of (E,E)-bis(2-bromovinyl) selenide and (E,E)-bis(1-bromo-1-hexen-2-yl) selenide with terminal alkynes was found to proceed at room temperature involving both bromine atoms and the selanyl function. As a result, new bis-(1,3-enynyl) selenides and enediyne hydrocarbons are formed with a complete retention of the stereoconfiguration of the initial selenides. Due to steric hindrances in the cross-coupling at the selenyl function in the case of (E,E)-bis(1-bromo-1-hexen-2-yl) selenide, the second process is realized to a lesser extent than with unsubstituted (E,E)-bis(2-bromovinyl) selenide.

1. Introduction

Sonogashira cross-coupling of vinyl chlorides, bromides, iodides, and triflates with terminal acetylenes in a presence of Pd(0) or Pd(II)/CuI while using amine as a base is one of the effective methods for synthesis of enyne hydrocabons [1,2,3,4,5]. Recently, new Pd catalytic systems such as crystallized Pd/Cu nanoparticles on activated carbon [6] and a zeolite-supported Pd catalyst [7] were suggested and studied in Sonogashira cross-couplings of aryl halides with terminal acetylenes. At the same time, unsaturated chalcogenides could be convenient alternatives to halides as a source of electrophilic reagents in the Sonogashira reactions since the oxidative addition of organyl selenides at palladium proceeds faster than the addition of organic halides because the carbon-selenium bond is more labile than the carbon-halogen bond [8]. Nevertheless, so far in Sonogashira cross-coupling, only vinyl tellurides were introduced [9]. Thus, Z-vinyl tellurides afford corresponding enyne hydrocarbons with the retention of the Z-configuration in the reactions of cross-coupling with terminal acetylenes catalyzed with PdCl₂/CuI [10]. Similarly, Z,Z-bis(vinyl) tellurides react with terminal acetylenes at the same conditions affording endiyne hydrocarbons of the Z-configuration. However, divinyl selenides were completely inert in these reactions, and initial compounds usually were isolated unchanged no matter what palladium catalyst was taken [11]. In a case of E-1-bromovinyl selenides, in the cross-coupling reactions with terminal acetylenes catalyzed with Pd(PPh₃)₄, only one bromine atom was involved; the selanyl group did not participate in the reaction. As a result, only corresponding Z-2-organylseleno-1,3-enynes were isolated as the reaction products [12]. Similarly, affording E-1-arylselanyl substituted 1,3-enynes, which retain the configuration of the initial vinyl group; the reaction of E-1-iodo-2-arylseleno ethylenes with terminal acetylenes is realized [13]. In addition, in this case, the selanyl function does not participate in the reaction. To carry out cross-coupling of both tellanyl and selanyl functions in (Z,Z)- and (E,E)-bis(vinyl) chalcogenides with terminal acetylenes, authors [14] managed using nickel catalyst Ni(dppe)Cl₂ combined with CuI. In addition, in this case, the reaction took place with the retention of the chalcogenides’ initial configuration and formation of the corresponding enynes. Only in a case of acetylenic selenides using system PdCl₂(PPh₃)₂/Cu(OAc)₂∙H₂O in DMF, it was possible to realize the Sonogashira reaction with participation of the selanyl group. An interaction of aryl ethynyl butyl selenide with terminal acetylenes led here to the formation of diacetylenic hydrocarbons in high yields [15].

Previously, during an investigation of the electrophilic addition reaction to unsaturated compounds of selenium dibromide generated in situ from selenium and bromine, we synthesized (E,E)-bis(2-bromovinyl) selenide (1) which was prepared quantitatively by the stereoselective SeBr₂ addition to acetylene in CCl₄ at a 10-12 bar pressure in the autoclave [16]. The alkene-to-alkyne transfer reaction of bis(2-bromoethyl) selenide with 1-hexyne in acetonitrile [17] afforded (E,E)-bis(1-bromo-1-hexen-2-yl) selenide (2a), an analog of the selenide 1 in which α-protons are substituted with butyl groups (Scheme 1).

2. Results and Discussion

The aim of this work is to compare Sonogashira Pd-catalyzed cross-coupling of unsaturated (E,E)-bis(2-bromovinyl) selenide (1) and substituted at α-carbons (E,E)-bis(1-bromo-1-hexen-2-yl) selenide (2a) with terminal acetylenes.

In this work we prepared selenide 1 in 72% yield by the electrophilic addition of selenium dibromide to acetylene in dichlorometane at atmospheric pressure and room temperature (Scheme 2).

As compared to the synthesis of selenide 1 in an autoclave [16], the convenient method of compound 1 preparation at atmospheric pressure makes this reagent more available.

This approach was also used in the regio- and stereoselective synthesis of selenides 2a,b in a high yield by the addition to 1-hexyne of selenium dibromide, similarly generated in situ from elemental selenium and bromine (Scheme 3). This “one pot” method allows you to exclude the intermediate stage of the bis(2-bromoethyl) selenide synthesis by the bubbling of ethylene through a SeBr₂ solution in CHCl₃ or CCl₄ and consequent isolation of the product [18]. Bis(2-bromoethyl) selenide used in the preparation method depicted in the Scheme 1 is, in fact, a substitute for SeBr₂, and, though the alkene-to-alkyne transfer reaction affords compound 2a in a very high yield, the introduction of gaseous ethylene in the overall process makes it more complicated.

The reaction of thus-prepared SeBr₂ with 1-hexyne was carried out at room temperature in dichloromethane and afforded the product as a mixture of E,E-(2a) and E,Z-(2b) stereoisomers in a 4:1 ratio via the anti-Markovnikov anti- and syn-addition of selenium dibromide to 1-hexyne with a predominance of the anti-addition. Previously, we noticed a similar anti-Markovnikov addition with a predominance of the anti-addition for the reaction of selenium dichloride and dibromide with propargyl bromide which was also realized in chloroform at room temperature [19].

The structure of the selenides 2a and 2b that were prepared was confirmed by ¹H and ¹³C NMR spectra. In particular, the ¹H NMR spectrum of the selenide 2a is characterized by a singlet signal of the olefinic proton at δ 6.45 ppm and doublet satellite signals with a splitting constant ³J_SeH 6.4 Hz due to the interaction with the selenium atom pointing to a cis-configuration of H and Se atoms in the molecule [19,20,21] and, correspondingly, to the anti-Markovnikov addition of SeBr₂ to 1-hexyne. In the selenide 2b, two singlet signals of the olefinic protons at δ 6.30 and 6.62 ppm also show doublet satellite signals with the splitting constants ³J_SeH 6.4 and 8.4 Hz, correspondingly, pointing here to cis- and trans-configurations of the appropriate fragments and hence to the anti-Markovnikov addition of SeBr₂ to both 1-hexyne molecules [19,20,21]. It is worthwhile to note that in the case of the Markovnikov addition, in the molecules 2a and/or 2b, geminal splitting constant ²J_SeH 20.5 Hz was expected [21]. The anti-Markovnikov addition of SeBr₂ to 1-hexyne is evidenced also from direct splitting constant ¹J_CSe 110.4 Hz between ¹³C and ⁷⁷Se atoms in the =C(Bu)-Se fragment and the splitting constant through two bonds ²J_SeC 20.7 Hz between ¹³C and ⁷⁷Se atoms in the =CH=C-Se fragment [22] in the ¹³C NMR spectra of selenide 2a.

Presence in the selenides 1 and 2a of the bromine atoms in the trans-position to the selenium atom makes them convenient starting compounds for the synthesis of bis-enynic selenides with the predetermined E-configuration via the Sonogashira reaction. Taking into account the results of the investigations [11,12,13], one would expect that the process should be chemoselective.

However, quite unexpectedly, cross-coupling of the selenide 1 with the terminal acetylenes such as phenylacetylene (3a), 1-hexyne (3b), and trimethyl ethynyl silane (3c) taken in three-fold excess, in a presence of Pd(PPh₃)₄ and CuI, and diethylamine as a base, resulted in formation both of expected bis-enynic selenides—bis[(E)-4-phenyl-1-buten-3-ynyl] selenide (4a), di[(E)-1-octen-3-ynyl] selenide (4b), and bis[(E)-4-(trimethylsilyl)-1-buten-3-ynyl] selenide (4c), correspondingly, in which configuration of the parent selenide 1 was retained, and endiynes—(E)-1,6-diphenyl-3-hexen-1,5-diyne (5a), (E)-7-tetradecen-5,9-diyne (5b), and trimethyl[(E)-6-(thimethylsilyl)-3-hexen-1,5-diynyl] silane (5c), which also retained the configuration of the parent selenide 1 (Scheme 4).

In accordance with the classical scheme of the cyclic catalytic reaction involving the formation of copper acetylides and diacetylenic Pd complexes which undergo further to the reductive elimination of acetylide-anions [4,5] the diacetylenes 6a-c are formed in the reaction as the by-products. Their formation is confirmed both by the ¹H NMR spectra identical to the known ones and by the corresponding molecular ions in mass spectra of the compounds isolated.

According to the ¹H NMR spectra of the reaction mixtures efficiency of the selanyl function substitution as compared to the bromine atom substitution in the reaction, it depends greatly on the terminal acetylene nature. The ratio of selenide 4:endiyne 5 is 1:3 for phenylacetylene (3a), 1:0.9 for 1-hexyne (3b), and 1:1.1 for trimethyl ethynyl silane (3c). Yields of selenide 4, at that, vary from 21% for compound 4a to 51% for compound 4b; yields of endiynes 5 vary from 18% for compound 5c to 65% for compound 5a.

The structures of the selenides 4a–c are confirmed by ¹H and ¹³C NMR data, GC-MS data, as well as elemental analyses. In the ¹H NMR spectra, two doublet proton signals with the splitting trans-constant (³J 15.6–15.8 Hz) correspond to the ≡C-CH=CH-Se group of the E-configuration. The ¹³C NMR spectra are characterized by low-field signals of the CH= carbons adjacent to the acetylenic bond (δ 114.60–115.53 ppm) and high-field carbon signals of the =CH-Se group (δ 128.4–132.22 ppm).

E-Enediynes 5a–c formed in the reactions are known [17,19,20,21] and moreover are commercially available compounds. They are identified by a comparison of the ¹H NMR spectra with the known spectra of E- [23,24] and Z-isomers [23,25,26] of the corresponding enediynes as well as by mass- spectra demonstrating pronounced molecular ions.

In order to clear out the influence of the substituted bis(2-bromovinyl) selenide structure on chemoselectivity of the Sonogashira reaction, we carried out cross-coupling of the selenide 2a with phenylacetylene (3a), 1-hexyne (3b), trimethyl ethynyl silane (3c), 2-propynol-1 (3d), 2-methyl-3-butyn-2-ol (3e) taken in three-fold excess as in a case of selenide 1. The conditions of the reaction were the same as for selenide 1, and, as a catalyst, Pd(PPh₃)₄ was used in a presence of CuI and diethylamine.

It was found that in this case the reaction mostly proceeded as a substitution of bromine atoms with the acetylenic function to give corresponding bis-4-substituted (E,E)-bis[1-butyl-1-buten-3-yn-yl] selenides 7a–e which retain the configuration of the parent selenide 2a (Scheme 5). Selenides 7a–e were isolated from the reaction mixtures by column chromatography on silica gel.

Formation of these products was confirmed by the ¹H, ¹³C NMR spectroscopy, and GC-MS data. The corresponding molecular ions are observed in the GC-MS spectra as well as fragment ions [M − R]⁺ and the ions characteristic of the particular selenide with regard to the structure of the acetylenic moiety. In the ¹H NMR spectra, the singlet (in the case of the selenides 7a,c,e) or triplet (in the case of the selenides 7b,d due to the interaction through five bonds in the =CH-C≡C-CH₂ system) signals of olefinic protons were detected. In turn, these signals are accompanied by doublet satellite signals with the splitting constants ³J_SeH 4.2–5.1 Hz due to the interaction with the selenium atom which confirm the cis-configuration of Se and H atoms in the molecule [19,20,21]. Presence in the ¹³C NMR spectra of the interaction between the ¹³C and ⁷⁷Se atoms through one bond in the =C-Se moiety with the splitting constant ¹J_CSe 100.0–114.4 Hz and through two bonds in the CH=C-Se fragment with ²J_CSe 14.2–15.1 Hz confirms the given structures of the selenides 7. In the case of the selenide 7c, the structure was unambiguously confirmed by 2D ¹H-¹³C NMR spectroscopy hmbc ¹³C.

Cross-coupling at the selanyl function, as in the case of selenide 1, was also found for selenide 2a (Scheme 5). Though we failed to isolate the corresponding enediynes 8a–e in a pure form by column chromatography, they were unequivocally identified by the corresponding molecular and fragment ions on analyzing the GC-MS spectra of the product mixtures obtained. However, in contrast to the reaction of the selenide 1 with terminal acetylenes in which the ratio of the selenides 4 and enediynes 5 vary from 1:3 to 1:0.9, efficiency of cross-coupling at the selanyl function for selenide 2a is significantly lower: enediynes 8a–e are formed either in the insignificant (a ratio selenide 7: enediyne 8 is 1:0.2 for acetylene 3a, 1:0.18 for acetylene 3c, 1:0.14 for acetylene 3e, according to ¹H NMR data) or in the trace amounts. So, efficiency of cross-coupling at the selanyl function in the selenide 2a is significantly influenced by reduced steric availability of selenium in the molecule.

As in the case of selenide 1, in the reaction of selenide 2a, the diacetylenes 6a–e, which are the commercially available products, are formed as the by-products. Their formation was confirmed both by the ¹H NMR spectra identical to the known ones and by the corresponding molecular ions in the GC-MS spectra of the reaction mixtures.

3. Materials and Methods

3.1. General Information

The ¹H (400.13 MHz) and ¹³C (100.61 MHz) spectra as well as ¹³C-Jmod were recorded on a Bruker Avance DPX 400 spectrometer (Bruker BioSpin GmbH, Rheinstetten, Germany) in 5–10% CDCl₃ solutions using the solvent proton (δ 7.27 ppm) and carbon (δ 77.16 ppm) signals as internal standards. Electron ionization-mass spectra (EI-MS) were determined on a Shimadzu QP-5050A (Shimadzu Corporation, Kyoto, Japan) at 70 eV. Elemental analyses were performed on a Thermo Scientific Flash 2000 Elemental Analyzer (Thermo Fisher Scientific Inc., Milan, Italy). Melting points were determined on a Kofler Hot-Stage Microscope PolyTherm A apparatus (Wagner & Munz GmbH, München, Germany). Dry 1,4-dioxane was used as a solvent. Pd(PPh₃)₄, CuI, and terminal acetylenes were purchased from Alfa-Aesar.

3.2. Synthesis of Starting Selenide 1

(E,E)-Bis(2-bromovinyl) selenide (1). A methylene chloride solution saturated with acetylene was obtained by bubbling acetylene into methylene chloride (40 mL) for 1 h at room temperature. A mixture of selenium powder (0.79 g, 10 mmol) and bromine (1.6 g, 10 mmol) in methylene chloride (5 mL) was stirred at ambient temperature until the solid disappeared. The obtained solution of selenium dibromide was added dropwise for 20 min to the methylene chloride solution saturated with acetylene (40 mmol) at room temperature. During the addition, bubbling of acetylene was continued. After addition, acetylene was bubbled into the reaction mixture for 3 h at room temperature. After evaporation of the solvent, the crude product was purified by column chromatography on silica gel (eluent: hexane → hexane/chloroform 9:1) to give selenide 1 (2.09 g, 72% yield) as a yellowish oil.

¹H NMR (400 MHz, CDCl₃): δ 6.43 (d, ³J = 13.7 Hz, 2H, 2CHBr=), 6.91 (d, ³J = 13.7 Hz, 2H, 2SeCH=). Lit. [16]. ¹H NMR (CDCl₃): δ 6.43 (d, 2H, ³J = 13.3 Hz, 2H, 2CHBr=), 6.91 (d, ³J = 13.3 Hz, 2H, 2SeCH=).

3.3. Synthesis of Selenides 2a,b

A mixture of selenium powder (0.16 g, 2 mmol) and bromine (0.32 g, 4 mmol) in methylene chloride (1 mL) was stirred 2 h at ambient temperature until the solid disappeared. The solution of SeBr₂ thus prepared was slowly added dropwise at ambient temperature to a solution of 1-hexyne (0.35 g, 4.2 mmol) in methylene chloride (20 mL), and the reaction mixture was stirred for 12 h. Evaporation of the solvent in a vacuum gave selenide 2 (0.755 g, 94%) as a mixture of E,E- and E,Z-isomers in a 4:1 ratio according to the ¹H NMR data. Selenide 2a was isolated from the mixture by column chromatography on silica gel (eluent: hexane → hexane/chloroform (9:1)).

(E,E)-Bis(1-bromo-1-hexen-2-yl) selenide (2a).

¹H NMR (400 MHz, CDCl₃): δ 0.94 (t, ³J = 7.3 Hz, 6H, 2CH₃), 1.37 (sextet, ³J = 7.4 Hz, 4H, 2CH₂), 1.52 (quintet, ³J = 7.6 Hz, 4H, 2CH₂), 2.44 (t, ³J = 7.6 Hz, 4H, 2CH₂,), 6.45 (s, ³J_SeH(cis) = 6.4 Hz, 2H, 2=CH). Lit. [17]: 0.96–0.93 (m, 6H), 1.41–1.32 (m, 4H), 1.56–1.48 (m, 4H), 2.46–2.42 (m, 4H), 6.45 (s, 2H).

¹³C NMR (100 MHz, CDCl₃): δ 14.03 (C⁶), 22.25 (C⁵), 29.81 (C⁴), 34.90 (C³), 107.53 (d, ²J_SeC = 20.7 Hz, =CH), 135.12 (¹J_CSe = 110.4 Hz, C-Se). Lit. [17]: 13.90, 22.12, 29.68, 34.77, 107.40, 134.97.

MS (EI), m/z (%): 404 (5) [M]⁺, 362 (1) [M − C₃H₆]⁺, 323 (6), 281 (3), 269 (2), 244 (9) [M − BrC≡CC₄H₉]⁺, 202 (26), 187 (3), 173 (2), 163 (12), 145 (7), 133 (8), 119 (27), 107 (5), 93 (12), 79 (64), 67 (21), 57 (53), 41 (100) [C₃H₅]⁺.

Anal. calcd for C₁₂H₂₀Br₂Se (403.06): C, 35.76; H, 5.00; Br, 39.65; Se, 19.60%. Found: C, 35.62; H, 4.95; Br, 39.45; Se, 19.74%.

(E,Z)-Bis(1-bromo-1-hexen-2-yl) selenide (2b).

¹H NMR (400 MHz, CDCl₃): δ 0.94 (t, ³J = 7.3 Hz, 3H, CH₃), 0.95 (t, ³J = 7.6 Hz, 3H, CH₃), 1.36 (sextet, ³J = 7.4 Hz, 4H, 2CH₂), 1.53 (quintet, ³J = 7.5 Hz, 2H, CH₂), 1.56 (quintet, ³J = 7.5 Hz, 2H, CH₂), 2.48 (t, ³J = 7.5 Hz, 2H, CH₂), 2.59 (t, ³J = 7.2 Hz, 2H, CH₂), 6.30 (s, ³J_SeH(cis) = 6.4 Hz, 1H, =CH), 6.62 (s, ³J_SeH(trans) = 8.4 Hz, 1H, =CH).

¹³C NMR (100 MHz, CDCl₃): δ 14.03(C⁶), 21.77(C⁵), 30.10(C⁴), 35.23(C³), 38.38(C³), 104.47 (=CH), 116.31 (=CH), 135.11 (C-Se).

The ¹H and ¹³C NMR spectra of the selenides 2a and 2b see in Supplementary Materials.

3.4. Cross-Coupling of (E,E)-bis(2-bromovinyl) selenide (1) with Terminal Acetylenes 3

Cross-coupling of selenide 1 with phenylacetylene (3a). A mixture of CuI (0.029 g, 0.15 mmol,), Pd(PPh₃)₄ (0.116 g, 0.1 mmol), and diethyl amine (0.29 g, 4 mmol) in 1,4-dioxane (2.5 mL) was stirred in an argon atmosphere at ambient temperature for 15 min; selenide 1 (0.145 g, 0.5 mL) in 1,4-dioxane (0.5 mL) was added to the resulting solution; stirring was continued for 1 h, and then, into the reaction mixture, acetylene 3a was introduced in 1,4-dioxane (1 mL). After additional stirring for 24 h in an argon atmosphere at room temperature, the resulting mixture was diluted with water (25 mL) and extracted with chloroform (3 × 15 mL); the chloroform extract was dried over CaCl₂. After removal of the solvent and excess of the reagents in a vacuum, a residue was rinsed with hexane. From the obtained reaction mixture (0.255 g) containing, according to the ¹H NMR data, selenide 4a and endiyne 5a in a ratio 1:3 as well as diphenyl diacetylene (6a), the products 4a and 5a were isolated by column chromatography on silica gel (eluent: hexane → hexane/chloroform (9:1) → chloroform).

Bis[(E)-4-phenyl-1-buten-3-ynyl] selenide (4a), 0.035 g (21%), brown oil.

¹H NMR (400 MHz, CDCl₃): δ 6.14 (d, ³J 15.8 Hz, 1H, =CH-C≡,), 7.09 (d, ³J 15.8, 1H, SeCH=), 7.29–7.33 (m, 6H_arom), 7.43–7.46 (m, 4H_arom).

¹³C NMR (100 MHz, CDCl₃): δ 87.58 (≡C), 91.09 (≡C), 114.72 (=CH-C≡), 123.15 (C_arom), 128.51 (C_aromH), 130.83 (C_aromH), 131.59 (=CHSe), 131.64 (C_aromH).

MS (EI), m/z (%): [M]⁺ 334 (16), 276 (9), [M - H₂Se]⁺ 252 (100), 239 (10), 226 (11), 176 (4), 152 (12), 139 (7), 126 (58), 115 (24), 101 (10), 77 (25).

Anal. calcd for C₂₀H₁₄Se (333.28): C, 72.07; H, 4.23; Se, 23.69%. Found: C, 72.15; H, 4.47; Se, 23.89%.

(E)-1,6-Diphenyl-3-hexen-1,5-diyne (5a), 0.074 g (65%), light-brown needles, mp 110 °C. Lit. [23]: mp. 110–112 °C.

¹H NMR (400 MHz, CDCl₃): δ 6.27 (s, 2H, =CH), 7.29–7.33 (m, 6H_arom), 7.43–7.46 (m, 4H_arom). Lit. E-isomer [23]: 6.29 (s, 2H, =CH), 7.26–7.36 (m, 6H_arom), 7.45–7.49 (m, 4H_arom); Z-isomer [23]: 6.10 (s, 2H, =CH), 7.33–7.36 (m, 6H_arom), 7.50–7.54 (m, 4H_arom)

MS (EI), m/z (%): [M]⁺ 228 (100), [M-C₂H₂]⁺ 202 (14), 150 (5), 126 (20), 113 (26), 100 (9), 77 (3).

Cross-coupling of selenide 1 with 1-hexyne (3b). Similarly, a mixture of CuI (0.035 g, 0.18 mmol), Pd(PPh₃)₄ (0.114 g, 0.1 mmol), diethyl amine (0.29 g, 4 mmol), selenide 1 (0.148 g, 0.51 mmol), acetylene 3b (0.255 g, 3.1 mmol) in 1,4-dioxane (6 mL) was afforded after 20 h stirring, a mixture of products (0.392 g) containing, according to the ¹H NMR data, selenide 4b and endiyne 5b in a ratio 1:0.9 as well as dodeca-5,7-diyne (6b). The products were isolated by the column chromatography on silica gel (eluent: hexane → hexane/chloroform (9:1) → chloroform).

Di[(E)-1-octen-3-ynyl] selenide (4b), 0. 075 g (51%), brown oil.

¹H NMR (400 MHz, CDCl₃): δ 0.92 (t, ³J = 7.2 Hz, 6H, 2CH₃), 1.42 (sextet, ³J = 7.3 Hz, 4H, 2CH₂), 1.52 (quintet, ³J = 7.2 Hz, 4H, 2CH₂), 2.31 (t d, ³J = 6.9 Hz, ⁵J = 2.2 Hz, 4H, 2 =CH-C≡C-CH₂), 5.89 (d t, ³J = 15.8 Hz, ⁵J = 2.2 Hz, 2H, 2 =CH-C≡C-CH₂), 6.84 (d, ³J 15.8 Hz, 2H, 2SeCH=).

¹³C NMR (100 MHz, CDCl₃): δ 13.71 (CH₃) 19.29 (CH₂-CH₃), 22.10 (CH₂-C≡), 30.82 (CH₂), 78.86 (C≡), 92.28 (C≡), 115.50 (=CH-C≡), 128.91 (=CHSe).

MS (EI), m/z (%): [M]⁺ 294 (30), [M − C₃H₇]⁺ 251 (18), 209 (28), 195 (55), 183 (6), 169 (9), 155 (24), 141 (48), 128 (100), 115 (57), 105 (11), 91 (45), 77 (30), 65 (36).

Anal. calcd for C₁₆H₂₂Se (293.31): C, 65.51; H, 7.56; Se, 26.93%. Found: C, 65.87; H, 7.35; Se, 26.74%.

(E)-7-Tetradec-5,9-diyne (5b), 0.030 g (31%), brown oil.

¹H NMR (400 MHz, CDCl₃): δ 0.91 (t, ³J = 7.2 Hz, 6H, 2CH₃), 1.39–1.44 (sextet, ³J = 7.3 Hz, 4H, 2CH₂), 1.48–1.55 (quintet, ³J = 7.2 Hz, 4H, 2CH₂), 2.25 (t, ³J = 7.0 Hz, 4H, 2CH₂), 5.88 (s, 2H, CH=CH). Lit. Z-isomer [25]: 0.90 (t, 6H, ³J = 7.2 Hz, 2CH₃), 1.48 (m, 8H, 4CH₂), 2.37 (t, ³J = 6.8 Hz, 4H, 2CH₂), 5.70 (s, 2H, CH=CH).

MS (EI), m/z (%): [M]⁺ 188 (57), [M – CH₃]⁺ 173 (3), [M − C₃H₇]⁺ 145 (22), [M - C₄H₉]⁺ 131 (78), 117 (88), 115 (77), 105 (38), 91 (100), 77 (55), 63 (27), 51 (31).

Cross-coupling of selenide 1 with trimethyl ethynyl silane (3c). Similarly, a mixture of CuI (0.030 g, 0.16 mmol), Pd(PPh₃)₄ (0.116 g, 0.1 mmol), diethyl amine (0.298 g, 4.1 mmol), selenide 1 (0.149 g, 0.51 mmol), acetylene 3c (0.301 g, 3.1 mmol) in 1,4-dioxane (6 mL) was afforded after 24 h stirring, a mixture of products (0.278 g) containing, according to the ¹H NMR data, selenide 4c and endiyne 5c in a ratio 1:1.1 as well as 1,4-bis(trimethylsilyl) butadiyne (6c). The products were isolated by the column chromatography on silica gel (eluent: hexane → hexane/chloroform (4:1) → chloroform).

Bis[(E)-4-(trimethylsilyl)-1-buten-3-ynyl] selenide (4c), 0.046 g (28%), light-yellow oil.

¹H NMR (400 MHz, CDCl₃): δ 0.20 (s, 18H, 2Si(CH₃)₃), 5.93 (d, ³J = 15.6 Hz, 2H, 2=CH-C≡), 7.04 (d, ³J = 15.6 Hz, 2H, 2=CHSe).

¹³C NMR (100 MHz, CDCl₃): δ -0.05 [(CH₃)₃Si], 96.41 (≡C-Si), 102.75 (≡C-C=), 114.60 (=CH-C≡), 132.23 (=CH-Se).

MS (EI), m/z (%): [M]⁺ 326 (5), [M − CH₃]⁺ 311 (4), 295 (3), 223 (2), 173 (10), 155 (2), 145 (10), 123 (2), 108 (10), [(CH₃)₃Si]⁺ 73 (100).

Anal. calcd for C₁₄H₂₂Si₂Se (325.46): C, 51.67; H, 6.81; Se, 24.26%. Found: C, 51.23; H, 6.35; Se, 23.95%.

Trimethyl [(E)-6-(trimethylsilyl)-3-hexen-1,5-diynyl] silane (5c), 0.039 g (18%), light-yellow crystals, mp 75 °C. Lit. [27]: 75–76 °C.

¹H NMR (400 MHz, CDCl₃): δ 0.18 (s, 18H, 2(CH₃)₃Si), 5.99 (s, 2H, CH=CH). Lit. E-isomer [24]: 0.17 (s, 18H, 2Si(CH₃)₃), 5.99 (s, 2H, CH=CH). Z-isomer [26]: 0.20 (s, 18H, 2Si(CH₃)₃), 5.88 (s, 2H, CH=CH).

MS (EI), m/z (%): [M]⁺ 220 (16), [M − CH₃]⁺ 205 (100), [M - (CH₃)₃Si]⁺ 147 (2), 145(6), 107 (2), 95 (24), [(CH₃)₃Si]⁺ 73 (54).

The ¹H and ¹³C NMR spectra of the selenides 4b,c see in Supplementary Materials.

3.5. Cross-Coupling of (E,E)-Bis(1-bromo-1-hexen-2-yl) selenide (2a) with Terminal Acetylenes 3

Cross-coupling of selenide 2a with phenylacetylene (3a). A mixture of CuI (0.029 g, 0.15 mmol,) Pd(PPh₃)₄ (0.116 g, 0.1 mmol), and diethyl amine (0.29 g, 4 mmol) in 1,4-dioxane (2.5 mL) was stirred in an argon atmosphere at ambient temperature for 15 min; selenide 2a (0.202 g, 0.5 mL) in 1,4-dioxane (0.5 mL) was added to the resulting solution; stirring was continued for 1 h, and then, into the reaction mixture, acetylene 3a was introduced in 1,4-dioxane (1 mL). After additional stirring for 20 h in an argon atmosphere at room temperature, the resulting mixture was diluted with water (25 mL) and extracted with chloroform (3 × 15 mL); the chloroform extract was dried over CaCl₂. After removal of the solvent and excess of the reagents in a vacuum, a residue was dissolved in chloroform and filtered through silica gel. From the obtained product mixture containing, according to the ¹H NMR data, selenide 7a and endiyne 8a in a ratio 1:0.2 as well as diacetylene 6a, the compound 7a was isolated by column chromatography on silica gel (eluent: hexane → hexane/chloroform (1:1) → chloroform). Endiyne 8a was identified in a mixture with selenide 7a and diacetylene 6a by GC-MS.

(E,E)-Bis[1-butyl-4-phenyl-1-buten-3-yn-1-yl] selenide (7a), 0.083 g (38%).

¹H NMR (400 MHz, CDCl₃): δ 0.98 (t, ³J = 7.4 Hz, 6H, CH₃), 1.44 (sextet, ³J = 7.4 Hz, 4H, CH₂), 1.63 (quintet, ³J = 7.4 Hz, 4H, CH₂), 2.70 (t, ³J = 7.4 Hz, 4H, CH₂), 6.06 (s, ³J_SeH 5.0 Hz, 2H, =CH), 7.33–7.36 (m, 6H_arom), 7.44–7.47 (m, 4H_arom).

¹³C NMR (100 MHz, CDCl₃): δ 14.10 (C⁸), 22.34 (C⁷), 31.27 (C⁶), 35.67 (C⁵), 86.68 (≡C), 94.37 (≡C), 114.57 (²J_CSe = 15.1 Hz, =CH), 123.59 (C_arom), 128.34 (C_arom), 128.52 (C_arom), 131.50 (C_arom), 148.97 (¹J_CSe = 100.0 Hz, C-Se).

MS (EI), m/z (%): 446 (4) [M]⁺, 417 (2) [M − C₂H₅]⁺, 403 (12) [M − C₃H₇]⁺, 389 (4) [M − C₄H₉]⁺, 369 (2) [M − C₆H₅]⁺, 359 (4), 347 (12), 343 (4), 332 (4), 323 (3), 309 (3), 293 (4), 279 (13), 265 (27), 253 (9), 241 (5), 229 (3), 219 (9), 202 (11), 165 (28), 152 (26), 191 (8), 141 (47), 128 (27), 115 (100), 102 (12), 91 (43), 77 (26) [C₆H₅]⁺, 67 (18), 55 (25), 43 (19), 41 (56).

Anal. calcd for C₂₈H₃₀Se (445.50): C, 75.49; H, 6.79; Se, 17.72%. Found: C, 75.67; H, 6.90; Se, 17.50%.

(E)-3-Butyl-1,6-diphenyl-3-hexen-1,5-diyne (8a).

MS (EI), m/z (%): 284 (100) [M]⁺, 269 (2) [M − CH₃]⁺, 253 (18), 241 (93) [M -C₃H₇]⁺, 226 (28), 215 (17), 202 (10), 191 (11), 178 (12), 165 (25), 152 (7), 139 (16), 127 (28), 115 (78), 106 (6), 91 (18), 77 (23) [C₆H₅]⁺, 63 (20), 51 (15) [C₄H₃]⁺, 39 (17) [C₃H₃]⁺.

Cross-coupling of selenide 2a with hexyne (3b). Similarly, stirring for 20 h a mixture of CuI (0.021 g, 0.11 mmol), Pd(PPh₃)₄ (0.081 g, 0.07 mmol), diethyl amine (0.205 g, 2.8 mmol), selenide 2a (0.14 g, 0.35 mmol), and acetylene 3b (0.173 g, 2.1 mmol) in 1,4-dioxane (3.5 mL) afforded, after filtration through a layer of silica gel, a product mixture containing, according to the ¹H NMR data, selenide 7b and a trace of endiyne 8b as well as diyne 6b. Selenide 7b was isolated from the mixture by column chromatography on silica gel (eluent: hexane → hexane/chloroform (9:1) → chloroform). Endiyne 8b was identified in the product mixture by GC-MS.

(E,E)-Bis[1-butyl-1-octen-3-yn-1-yl] selenide (7b), 0.053 g (37%).

¹H NMR (400 MHz, CDCl₃): δ 0.93 (t, ³J = 7.2 Hz, 6H, 2CH₃), 0.92 (t, ³J = 7.2 Hz, 6H, 2CH₃), 1.34 (sextet, ³J = 7.3 Hz, 4H, 2CH₂), 1.44 (quintet, ³J = 7.3 Hz, 4H, 2CH₂), 1.47–1.55 (m, 8H, 2CH₂CH₂), 2.35 (d t, ³J = 6.7 Hz, ⁵J = 1.8 Hz, 4H, 2CH₂-C≡), 2.52 (t, ³J = 7.5 Hz, 4H, 2CH₂-C=), 5.76 (t, ⁵J = 1.8 Hz, ³J_SeH = 4.5 Hz, 2H, 2=CH).

¹³C NMR (100 MHz, CDCl₃): δ 13.70 (C¹²), 14.04 (C¹), 19.43 (C¹¹), 22.08 (C⁹), 22.30 (C²), 30.98 (C¹⁰), 31.12 (C³), 35.27 (C⁴), 88.33 (≡C), 95.40 (≡C), 115.05 (²J_SeC = 14.9 Hz, =C), 146.71 (¹J_CSe = 108.4 Hz, C-Se).

MS (EI), m/z (%): 406 (4) [M]⁺, 363 (11) [M − C₃H₇]⁺, 349 (4) [M − C₄H₉]⁺, 321 (4), 307 (15), 293 (3), 277 (3), 265 (7), 251 (8), 239 (3), 227 (3), 211 (3), 197 (8), 183 (7), 169 (8), 155 (10), 143 (9), 129 (10), 117 (11), 105 (17), 91 (41), 77 (38), 67 (28), 55 (44), 41 (100) [C₃H₅]⁺.

Anal. calcd for C₂₄H₃₈Se (405.52): C, 71.08; H, 9.45; Se, 19.47%. Found: C, 71.32; H, 9.70; Se, 19.54%.

(E)-7-Butyl-7-tetradecen-5,9-diyne (8b).

MS (EI), m/z (%): 244 (49) [M]⁺, 201 (6) [M − CH₃]⁺, 187 (17) [M − C₄H₉]⁺, 173 (10), 159 (41), 145 (92), 131 (75), 117 (79), 105 (42), 91 (73), 77 (37), 65 (29), 57 (23), 55 (42), 41 (100) [C₃H₅]⁺, 39 (32) [C₃H₃]⁺.

Cross-coupling of selenide 2a with trimethyl ethynyl silane (3c). Similarly, stirring for 20 h a mixture of CuI (0.044 g, 0.23 mmol), Pd(PPh₃)₄ (0.174 g, 0.15 mmol), diethyl amine (0.435 g, 6.0 mmol), selenide 2a (0.303 g, 0.75 mmol), and acetylene 3c (0.443 g, 4.5 mmol) in 1,4-dioxane (6 mL) afforded, after filtration through a layer of silica gel, a product mixture containing, according to the ¹H NMR and GC-MS data, selenide 7c and endiyne 8c in a ratio 1:0.18 as well as diyne 6c. Selenide 7c was isolated from the mixture by column chromatography on silica gel (eluent: hexane → hexane/chloroform (4:1) → chloroform). Endiyne 8c was identified in the product mixture by GC-MS.

(E,E)-Bis[1-butyl-4-(trimethylsilyl)-1-buten-3-ynyl] selenide (7c), 0.192 g (58%).

¹H NMR (400 MHz, CDCl₃): δ 0.20 (s, 18H, 2Si(CH₃)₃), 0.94 (t, ³J = 7.3 Hz, 6H, 2CH₃), 1.35 (sextet, ³J = 7.4 Hz, 4H, 2CH₂), 1.54 (quintet, ³J = 7.5 Hz, 4H, 2CH₂), 2.57 (t, ³J = 7.5 Hz, 4H, 2CH₂), 5.78 (s, ³J_SeH = 4.5 Hz, 2H, 2=CH).

¹³C NMR (100 MHz, CDCl₃): δ 0.04 (SiCH₃), 14.00 (C⁸), 22.14 (C⁷), 31.04 (C⁶), 35.58 (C⁵), 99.69 (≡C-Si), 101.95 (≡C-C=,) 114.53 (²J_SeC = 14.4 Hz, =CH), 150.52 (¹J_CSe = 111.7 Hz, C-Se).

MS (EI), m/z (%): 438 (2) [M]⁺, 396 (3) [M − C₃H₆]⁺, 365 (2) [M − (CH₃)₃Si]⁺, 307 (2), 293 (2), 245 (4), 227 (1), 183 (2), 155 (2), 145 (2), 135 (2), 121 (6), 105 (3), 83 (6), 73 (100) [(CH₃)₃Si]⁺, 59 (18) [(CH₃)₂SiH]⁺, 45 (8) [CH₃SiH₂]⁺.

Anal. calcd for C₂₂H₃₈Si₂Se (437.67): C, 60.37; H, 8.75; Se, 18.04%. Found: C, 60.61; H, 8.95; Se, 17.94%.

[(E)-4-Butyl-6-(trimethylsilyl)-3-hexen-1,5-diynyl] trimethyl silane (8c).

MS (EI), m/z (%): 276 (30) [M]⁺, 261 (36) [M − CH₃]⁺, 245 (25), 229 (3), 219 (15) [M − C₄H₉]⁺, 203 (4) [M − (CH₃)₃Si]⁺, 189(10), 173 (7), 159 (9), 145 (10), 131 (7), 123 (11), 121 (3), 109 (3), 97 (8), 83 (8), 73 (100) [(CH₃)₃Si]⁺, 59 (26) [(CH₃)₂SiH]⁺, 45 (19) [CH₃SiH₂]⁺.

Cross-coupling of selenide 2a with 2-propyn-1-ol (3d). Similarly, stirring for 72 h a mixture of CuI (0.029 g, 0.15 mmol), Pd(PPh₃)₄ (0.116 g, 0.1 mmol), diethyl amine (0.29 g, 4.0 mmol), selenide 2a (0.202 g, 0.5 mmol), and acetylene 3d (0.336 g, 6.0 mmol) in 1,4-dioxane (6 mL) afforded, after extraction with hexane and diethyl ether, a product mixture containing, according to the ¹H NMR data, selenide 7d and endiyne 8d as a trace as well as 2,4-hexadiyn-1,5-diol (6d). Selenide 7d was isolated from the mixture by column chromatography on silica gel (eluent: hexane → hexane/chloroform (4:1) → chloroform). Endiyne 8d was identified in the product mixture by GC-MS.

(E)-5-[(E)-1-Butyl-5-hydroxy-1-penten-3-ynyl] selanyl-4-nonen-2-yn-1-ol (7d), 0.042 g (24%).

¹H NMR (400 MHz, CDCl₃): δ 0.93 (t, ³J = 7.2 Hz, 6H, 2CH₃), 1.34 (sextet, ³J = 7.5 Hz, 4H, 2CH₂), 1.52 (quintet, ³J = 7.6 Hz, 4H, 2CH₂), 1.66 (br s, 2H, 2OH), 2.55 (t, ³J = 7.4 Hz, 4H, 2CH₂), 4.43 (d, ⁵J = 2.1 Hz, 4H, 2≡C-CH₂), 5.80 (t, ⁵J = 2.1 Hz, ³J_SeH = 4.2 Hz, 2H, 2=CH).

¹³C NMR (100 MHz, CDCl₃): δ 13.51 (C⁹), 22.24(C⁸), 31.13(C⁷), 35.44(C⁶), 51.85 (CH₂-OH), 82.63 (≡C), 92.12 (≡C), 113.83 (²J_SeC = 16.0 Hz, =CH), 149.50 (¹J_CSe = 100.2 Hz, =C-Se).

MS (EI), m/z (%): 354 (5) [M]⁺, 337 (4) [M - OH]⁺, 323 (1) [M − CH₂OH]⁺, 307 (5), 297 (1) [M - C₄H₉]⁺, 293 (4), 279 (2), 265 (3), 251 (4), 237 (4), 223 (5), 209 (4), 197 (4), 183 (6), 171 (4), 157 (6), 143 (10), 117 (10), 105 (9), 91 (31), 77 (30), 67 (40), 41 (100).

Anal. calcd for C₁₈H₂₆O₂Se (353.36): C, 61.18; H, 7.42; Se, 22.35%. Found: C, 61.06; H, 7.25; Se, 22.37%.

(E)-4-Butyl-4-octen-2,6-diyn-1,8-diol (8d).

MS (EI), m/z (%): 192 (51) [M]⁺, 145 (10), 131 (37), 115 (47), 103 (53), 91 (85), 77 (100) [C₆H₅]⁺, 63 (42) [C₅H₃]⁺, 55 (47) [HOCH₂C≡C]⁺, 51 (50) [C₄H₃]⁺, 43 (30) [C₃H₇]⁺, 41 (76) [C₃H₅]⁺, 39 (83) [C₃H₃]⁺.

Cross-coupling of selenide 2a with 2-methyl-3-butyn-2-ol (3e). Similarly, stirring for 20 h a mixture of CuI (0.019 g, 0.10 mmol), Pd(PPh₃)₄ (0.087 g, 0.07 mmol), diethyl amine (0.193 g, 2.6 mmol), selenide 2a (0.135 g, 0.33 mmol), and acetylene 3e (0.167 g, 2.0 mmol) in 1,4-dioxane (3.5 mL) afforded a product mixture containing, according to the ¹H NMR data, selenide 7e and endiyne 8e in a ratio 1:0.14 as well as 2,7-dimethyl-3,5-octadiyn-2,7-diol (6e). Selenide 7e was isolated from the mixture by column chromatography on silica gel (eluent: hexane → hexane/chloroform (4:1) → chloroform). Endiyne 8e was identified in the product mixture by GC-MS.

(E)-6-[(E)-1-Butyl-5-hydroxy-5-methyl-1-hexen-3-ynyl]selanyl-2-methyl-5-decen-3-yn-2-ol (7e), 0.051 g (38%).

¹H NMR (400 MHz, CDCl₃): 0.93 (t, ³J = 7.3 Hz, 6H, 2CH₃), 1.35 (sextet, ³J = 7.3 Hz, 4H, 2CH₂), 1.52 (quintet, ³J = 7.1 Hz, 4H, 2CH₂), 1.53 (s, 12H, 4CH₃), 2.53 (t, ³J = 7.4 Hz, 4H, CH₂), 5.77 (s, ³J_SeH = 5.1 Hz, 2H, 2=CH).

¹³C NMR (100 MHz, CDCl₃): δ 14.03 (C¹⁰), 22.24 (C⁹), 31.03 (C⁸), 31.58 (CH₃-C-OH), 35.40 (C⁷), 65.87 (C-OH), 79.19 (≡C), 98.73 (≡C), 113.93 (²J_CSe = 14.2 Hz, =C), 148.76 (¹J_CSe = 114.4 Hz, =C-Se).

MS (EI), m/z (%): 410 (1) [M]⁺, 377 (2), 363 (2), 351 (1) [M − C(CH₃)₂OH]⁺, 349 (2), 335 (2), 293 (1), 277 (2), 269 (1), 251 (2), 235 (2), 225 (1), 211 (2), 197 (2), 185 (3), 69 (2), 155 (2), 143 (3), 129 (2), 105 (6), 91 (11), 77 (12), 67 (10), 59 (19) [(CH₃)₂COH]⁺, 43 (100) [C₃H₇]⁺, 41 (24) [C₃H₅]⁺_.

Anal. calcd for C₂₂H₃₄O₂Se (409.46): C, 64.53; H, 8.37; Se, 19.28%. Found: C, 64.42; H, 8.20; Se, 19.14%.

(E)-5-Butyl-2,9-dimethyl-5-decen-3,7-diyn-2,9-diol (8e).

MS (EI), m/z (%): 248 (6) [M]⁺, 233 (6) [M − CH₃]⁺, 215 (5), 187 (4), 173 (5), 157 (3), 145 (9), 129 (6), 115 (6), 105 (7), 91 (11), 65 (6), 59 (7), 55 (7), 43 (100) [C₃H₇]⁺, 39 (7) [C₃H₃]⁺.

The ¹H and ¹³C NMR spectra of the selenides 7a–e see in Supplementary Materials.

4. Conclusions

(E,E)-Bis(2-bromovinyl) selenides were subjected to a cross-coupling reaction with terminal acetylenes in a presence of Pd/CuI catalysts at room temperature involving both the bromine atom and selanyl function and affording substituted bis(enynyl) selenides and endiyne hydrocarbons with complete retention of the initial selenide configuration. Due to a steric hindrance in a case of (E,E)-bis(1-bromo-1-hexen-2-yl) selenide, cross-coupling at selanyl function was realized to a lesser extent compared to unsubstituted (E,E)-bis(2-bromovinyl) selenide.