Synthesis of Aryl Alkynes via Copper Catalyzed Decarboxylative

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Synthesis of Aryl Alkynes via Copper Catalyzed Decarboxylative Alkynylation of 2-Nitrobenzoic Acids Yongqi Yu, Xiang Chen, Qianlong Wu, Da Liu, Liang Hu, Lin Yu, Ze Tan, Qingwen Gui, and Gangguo Zhu J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01047 • Publication Date (Web): 20 Jun 2018 Downloaded from http://pubs.acs.org on June 20, 2018

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The Journal of Organic Chemistry

Synthesis of Aryl Alkynes via Copper Catalyzed Decarboxylative Alkynylation of 2-Nitrobenzoic Acids Yongqi Yu,† Xiang Chen,† Qianlong Wu,† Da Liu,† Liang Hu,† Lin Yu,† Ze Tan,†,* Qingwen Gui‡,* and Gangguo Zhu§ †

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China ‡

College of Science, Hunan Agricultural University, Changsha 410128, P. R. China

§

Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, China [email protected], [email protected]

An efficient protocol for the synthesis of internal aryl alkynes was achieved via Cu-catalyzed decarboxylative cross-coupling reactions, and to the best of our knowledge, this is the first example of a Cu-catalyzed decarboxylative alkynylation of benzoic acids with terminal alkynes. This approach utilizes simple Cu salt as catalyst and O2, an abundant, clean and green material, as the oxidant. The reaction tolerates various functional groups and a variety of internal aryl alkynes were synthesized in 46-83% yields.

INTRODUCTION Aryl acetylenes are important structural scaffolds in organic molecules because they are not only widely present in many natural products but also can serve as important building blocks in organic synthesis, chemical biology and material science.1 As a result, the development of new methodology for the synthesis of acetylenes has always been area of intensive research. Among

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the various methods developed, the Corey-Fuchs reaction2 and Seyferth-Gilbert homologation reaction2c,3 are very efficient and popular. However, as for the synthesis of aryl acetylenes, the Pd-catalyzed Sonogashira cross-coupling reaction between a terminal alkyne and an aryl halide stood out from the rest and is the mostly preferred choice because of its incredibly wide range of functional group compatibility and operational simplicity.4 Despite its usefulness, however, the Pd-catalyzed Sonogashira cross-coupling reaction is not problem free. For example, it tends to fail when the cross-coupling is run between an electron-deficient alkyne and an aryl electrophile. It is reported that this type of coupling reaction usually only gives the desired product in low yield while the major product is the homodimer of the alkynes. Another major problem associated with the Pd-catalyzed coupling reactions is the high cost of Pd, and to remedy this situation, chemists have successfully developed similar couplings using cheap metal catalysts including Ni or Cu catalyst.5 Recently, carbon-carbon and carbon-heteroatom bond formations via transition metal catalyzed decarboxylation of phenyl carboxylic acids have attracted considerable attention6 because a large number of benzoic acids are commercially available. In addition, these benzoic acids are usually inexpensive and easy to store and handle. It is believed that in these coupling reactions, an aryl organometallic species is generated in situ from the corresponding aryl carboxylate through extrusion of a molecule of CO2. Subsequently this in situ generated aryl organometallic species can participate in transition metal catalyzed or mediated carbon-carbon and carbon-heteroatom bond formations. Works in this area by the groups of Gooßen,7 Myers,8 Su9 and others10 have demonstrated that aryl carboxylates can undergo a variety of decarboxylative couplings. It is interesting to note that in most of the reported cases, the aryl carboxylates serve mainly as aryl


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nucleophiles. Another common feature of these reported reactions is that a bimetallic catalyst system consisting of either Pd/Cu or Pd/Ag is often required for the desired decarboxylative coupling reactions.9b,10b,11 It is generally accepted that the Cu salt or Ag salt is used to decarboxylate the benzoic acid and the Pd catalyst is responsible for the subsequent cross-couplings. Once again the use of an expensive noble metal catalyst such as Pd makes these reactions much less practical. On the other hand, it would be highly desirable if a Cu-only catalyst system is employed because copper is considerably cheaper. Along this line, Gooßen in 2012 has shown that aryl ethers can be efficiently constructed from aryl carboxylates and silicate esters using copper(II) and silver(I) salt as catalysts.7b Even more surprisingly, they reported that by treating aromatic carboxylates with borate esters in the presence of simple copper catalyst, the aryl carboxylates will undergo highly selective ortho alkoxylation/protodecarboxylation to form various aryl ethers (Scheme 1, eq 1).7d Similar to the C-O bond formation, C-N bond formation between aryl carboxylic acids and amines or amides catalyzed by simple copper salt was also reported by Mainolfi and Jia (Scheme 1, eq 2).10c,10e At the mean time, Hoover and us reported Cu-catalyzed synthesis of aryl thioethers via the decarboxylative couplings between aryl carboxylic acids and thiols or DMSO (Scheme 1, eq 3).10h,12c Compared with Cu-catalyzed decarboxylative C-X bond formations, the analogous C-C bond formation is relatively underdeveloped. For example, Cu-catalyzed decarboxylative couplings between aryl carboxylic acids and benzothiazoles, benzimidazoles or benzoxazoles were reported by the groups of Hoover and Maiti (Scheme 1, eq 4).10d,10g It also should be mentioned that Liu also developed a Cu-catalyzed decarboxylative coupling between potassium polyfluorobenzoates and aryl iodides or bromides (Scheme 1, eq 5).10a As a part of our continuous interest in the development of new



reactions based on transition metal catalyzed decarboxylative couplings,12 we have attempted to couple terminal alkynes with aryl carboxylic acids. Herein we report that aryl alkynes can indeed be efficiently constructed from aryl carboxylic acids and alkynes using simple copper salt as catalyst (Scheme 1, eq 6).13 Scheme 1. Cu-catalyzed or mediated decarboxylative cross-coupling reactions

RESULTS AND DISCUSSION

At the outset, we commenced our investigations by choosing the 2-nitrobenzoic acid (1a) with phenylacetylene (2a) as the model reaction to study the decarboxylative cross-coupling reaction. To our delight, when we treated 1a with 4.0 equiv. of 2a in the presence of 20 mol % of CuCl2, 40 mol % of 1,10-phenanthroline and 2.0 equiv. of NaHCO3 in toluene under O2 at 150 oC for 24 h, the desired decarboxylative alkynylation product 3aa was isolated in 52% yield (Table 1, entry 1). To optimize the yield, we screened several copper salts, ligands, bases, oxidants, solvents and temperatures (Table 1). After a series of tests on the copper salts, we found that CuSO4 performed the best (Table 1, entries 2-6). The use of 2,2'-bipyridine or triphenylphosphine in place of


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1,10-phenanthroline resulted in much lower yields (Table 1, entries 7 and 8). The choice of base is crucial since no cross-coupled product was obtained in the absence of base (Table 1, entry 9). Subsequent screening of other bases proved NaHCO3 to be the optimal one while bases such as t-BuOK, Li2CO3 and Na2CO3 all gave inferior yields (Table 1, entries 10-12). Further investigations revealed that molecular oxygen is the most effective oxidant (Table 1, entries 3, 13-15). Further evaluation of solvents revealed the combination of toluene and DMF (3/1, 2 mL/0.3 mmol) was the best choice (Table 1, entries 16-19). It was observed that addition of 4 Å MS could improve the yield further to 76% (Table 1, entry 20). This may be due to the fact 4 Å MS can remove water from the reaction mixture and suppress the protodecarboxylation of 1a. Lowering the reaction temperature, catalyst loading or the amount of 2a actually decreased the product yields (Table 1, entries 21-24). Control experiment confirmed that copper catalyst is essential for the formation of 3aa (Table 1, entry 25). Therefore, we decided to set reacting 1a with 4.0 equiv. of 2a in the presence of 20 mol % of CuSO4, 40 mol % of 1,10-phenanthroline, 2.0 equiv. of NaHCO3 and 4 Å MS (50 mg/0.3 mmol) in toluene/DMF (3/1, 2mL/0.3 mmol) under O2 at 150 oC for 24 h as our optimized conditions. It should be mentioned that under our optimized conditions, analysis of the reaction mixture revealed that 2,2'-dinitro-1,1'-biphenyl, which could be derived from the homocoupling of 2-nitrobenzoic acid, was not formed at all. Table 1. Optimization of the reaction conditionsa



a

Reaction conditions: 1a (0.3 mmol), 2a (4.0 equiv.), Cu salt (20 mol %), ligand (40 mol %), base

(2.0 equiv.), solvent (2 mL), 150 oC, 24 h. bIsolated yield. cWithout base. d4 Å MS (50 mg) was added. eat 130 oC. fCu salt (10 mol %), ligand (20 mol %). g2a (2.0 equiv.). h2a (1.0 equiv.) i

Without Cu salt. With the optimized conditions in hand, the substrate scope of aryl carboxylic acids was

subsequently investigated and the results are shown in Table 2. It was observed that this cross-coupling reaction is compatible with various functional groups. Both electron-donating (methyl and methoxy) and electron-withdrawing (fluoro, chloro, bromo and trifluoromethyl) groups on the phenyl rings of the 2-nitrobenzoic acids were well tolerated and the desired products were obtained in moderate to good yields. In general, electron-deficient substituents on the


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benzoic acids led to higher yields (such as 3da and 3ha). Interestingly, the reaction of sterically hindered substrate 1m proceeded satisfactorily to afford the corresponding product 3ma, albeit in moderate yield. It should be noted that chloro and bromo substituted benzoic acids are also viable substrates even though they are well known to participate in Cu-catalyzed alkynylations. In addition, these halogens can provide the opportunity for further synthetic applications. We were disappointed to find that other aromatic carboxylic acids including 3-nitrobenzoic acid, 4-nitrobenzoic acid, 2-cyanobenzoic acid, 2-(trifluoromethyl)benzoic acid, 4-methoxybenzoic acid as well as the parent benzoic acid could not afford the desired alkynylation product 3 under our reaction conditions,14 indicating that both the electron density and the position of nitro group on the benzene rings of the benzoic acids are critical for the reaction to proceed (please see Chart S1 in SI for all the substrates tested). The need of a nitro group at the ortho position of the benzoic acids in this type of decarboxylative alkynylation may be due to the fact the nitro group can stabilize the Ar-Cu species generated in situ after decarboxylation through chelation.15 Table 2. Substrate scope of the benzoic acidsa.b



a

Reaction conditions: 1 (0.3 mmol), 2a (4.0 equiv.), CuSO4 (20 mol %), 1,10-phenanthroline (40

mol %), NaHCO3 (2.0 equiv.), toluene/DMF (3/1, 2 mL), 4 Å MS (50 mg), 150 oC, O2, 24 h. Isolated yield. bPlease see Table S1 in SI for isolated yield of 4a. The scope of the terminal alkynes was also explored under the optimized conditions (Table 3). Substituted phenyl alkynes with substituents at the meta or para positions of the aryl rings could react with 2-nitrobenzoic acid smoothly. Aromatic alkynes substituted with fluoro (3ad and 3ae), bromo (3af), alkyl (3ac, 3ag and 3ah), methoxy (3ai) and acetyl (3aj) groups worked well to generate the corresponding decarboxylative alkynylation products in 53-83% yields. Notably, an aromatic alkyne substituted with an unprotected amino group also provided the desired product 3ab in moderate yield. In contrast, substrates with a hydroxyl methyl, ester or formyl group on the para position of the phenyl acetylene failed to deliver the desired decarboxylative alkynylation products (not shown in Table 3). From the table, we can see that the attachment of electron-donating groups on the phenyl rings such as t-Bu (3ah) and methoxy (3ai) group led to slightly higher yields. Moreover, a series of aliphatic alkynes also proved to be good substrates,


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affording the desired decarboxylative alkynylation products in 54-68% yields (3ak-3ao). Table 3. Substrate scope of the terminal alkynesa,b

a

Reaction conditions: 1a (0.3 mmol), 2 (4.0 equiv.), CuSO4 (20 mol %), 1,10-phenanthroline (40

mol %), NaHCO3 (2.0 equiv.), toluene/DMF (3/1, 2 mL), 4 Å MS (50 mg), 150 oC, O2, 24 h. Isolated yield. bPlease see Table S1 in SI for isolated yield of 4b-o. Finally, a few synthetic utilities of the alkynylation products were investigated (Scheme 2). The Sonogashira coupling of 3fa with 2a provided 2-nitro-1,4-bis(2-phenylethynyl)benzene (5) in 86% yield (Scheme 2, eq 7). Meanwhile, the internal alkyne 1-nitro-2-(phenylethynyl)benzene (3aa) could be easily converted into 2-phenylindole (6) in good yield (Scheme 2, eq 8),16 which is an important structural scaffold in natural products and biologically active molecules. Scheme 2. Derivatization of the obtained products



To further understand the reaction mechanism, a series of control experiments were conducted (Scheme 3). When 2.0 equiv. of radical scavenger TEMPO was added to the reaction mixture, the yield was only slightly decreased (Scheme 3, eq 9), revealing that a radical pathway was probably not involved in the reaction process. Next we carried out the decarboxylative alkynylation reaction with a mixture of 1a and 1k (1:1 ratio), and we did not see any formation of nitrobenzene cross over dimerization product (Scheme 3, eq 10). Control experiment in the absence of phenylacetylene afforded nitrobenzene (7) and 2,2'-dinitro-1,1'-biphenyl (8) (Scheme 3, eq 11). These results, coupled with the observation that no 8 was formed under our optimized conditions, suggested that the involvement of a 2-nitrophenyl radical in the reaction was not likely. When we reacted 7 or 8 with phenylacetylene independently, no desired product 3aa was formed, showing that the formation of 3aa was not from 7 or 8 (Scheme 3, eq 13). Control experiment without 2-nitrobenzoic acid (1a) provided 1,4-diphenyldiacetylene (4a) only (Scheme 3, eq 12), which also failed to react with 1a to produce 3aa under the optimized conditions (Scheme 3, eq 14). This result suggested that 4a may not be the reaction intermediate either. Scheme 3. Control experiments


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Based on the above investigations and previous reports,17 a tentative reaction mechanism is proposed in Scheme 4. First, a Cu(II)-benzoate species A is generated by anion exchange, which gives an arylcopper(II) intermediate B via decarboxylation. Then, terminal alkyne interacts with B with the assistance of base to provide intermediate C, which is converted to the Cu(III) species D either by oxidation with O2 or by disproportion with Cu(II) species. Subsequent reductive elimination of D releases the target product and Cu(I) species. In the end, Cu(I) species is reoxidized to Cu(II) by O2 to fulfill the whole catalytic cycle. Scheme 4. Possible reaction mechanism



CONCLUSION In summary, we have developed an efficient method for the synthesis of internal aryl alkynes through Cu-catalyzed decarboxylative cross-coupling reactions. To the best of our knowledge, this is the first example of a Cu-catalyzed decarboxylative alkynylation reaction of benzoic acids with terminal alkynes. Our method features operational simplicity and use of simple CuSO4 as the catalyst. Another notable feature is that the reaction employs O2, an abundant, clean and green material, as the oxidant. Starting from diversely substituted 2-nitrobenzoic acids, a variety of internal aryl alkynes were synthesized in 46-83% yields. Further investigations on extending the substrate scope are currently ongoing in our laboratory and the results will be reported in due course. EXPERIMENTAL SECTION General. Unless otherwise noted, all reagents were obtained from commercial suppliers and used without further purification. All solvents were purified and dried according to standard methods prior to use. Column chromatography was carried out using silica gel (200-300 mesh) with


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petroleum ether/ethyl acetate as the eluent. 1H and

13

C NMR spectra were measured on a 400

MHz NMR spectrometer using CDCl3 as the solvent. The chemical shifts are given in δ relative to TMS, and the coupling constants are given in Hertz. The high-resolution mass spectra (HRMS) analyses were conducted using a TOF MS instrument with an ESI source or APCI source. Melting points were measured by a melting point instrument and were uncorrected. General procedure for copper-catalyzed decarboxylative alkynylation reaction of benzoic acids with terminal alkynes. Anhydrous CuSO4 (9.6 mg, 0.06 mmol), 1,10-phenanthroline (21.6 mg, 0.12 mmol), benzoic acid 1 (0.3 mmol), NaHCO3 (50.4 mg, 0.6 mmol) and 4 Å MS (50 mg) were added to a 25 mL Schlenk flask equipped with a high-vacuum PTFE valve-to-glass seal. The tube was evacuated and backfilled with O2 three times after which terminal alkyne 2 (1.2 mmol), freshly distillated toluene (1.5 mL) and DMF (0.5 mL) were added via syringe. The resulting mixture was stirred at 150 oC for 24 h. It was then cooled to room temperature, the reaction mixture was quenched with H2O (20 mL), extracted with ethyl acetate (20 mL × 3) and washed with brine. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography using petroleum ether/ethyl acetate as eluent to afford the desired product. 1-nitro-2-(phenylethynyl)benzene (3aa). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3aa as a yellow solid (50.9 mg, 76% yield); mp 39-41 oC; 1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 8.0 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.62-7.58 (m, 3H), 7.46 (t, J = 7.8 Hz, 1H), 7.40-7.36 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 149.6, 134.6, 132.8, 132.0, 129.2, 128.5, 128.4, 124.7, 122.4, 118.8, 97.1, 84.7; HRMS (ESI, m/z) calcd for C14H9NaNO2 [M + Na]+ 246.0531, found 246.0522.



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1-methyl-2-nitro-3-(phenylethynyl)benzene (3ba). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ba as a yellow liquid (37.7 mg, 53% yield); 1H NMR (400 MHz, CDCl3): δ 7.52-7.46 (m, 3H), 7.37-7.33 (m, 4H), 7.26-7.25(m, 1H), 2.37 (s, 3H);

13

C NMR (100 MHz, CDCl3): δ 152.6, 131.9, 131.1, 130.6, 130.1, 130.0, 129.1,

128.4, 122.0, 116.5, 95.4, 82.7, 17.6; HRMS (ESI, m/z) calcd for C15H11NaNO2 [M + Na]+ 260.0687, found 260.0682. 1-chloro-2-nitro-3-(phenylethynyl)benzene (3ca). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ca as a yellow solid (48.7 mg, 63% yield); mp 77-79 oC; 1H NMR (400 MHz, CDCl3): δ 7.55-7.50 (m, 3H), 7.47-7.36 (m, 5 H); 13C NMR (100 MHz, CDCl3): δ 150.9, 132.0, 131.1, 130.6, 130.0, 129.5, 128.4, 125.3, 121.4, 118.4, 97.0, 81.4; HRMS (ESI, m/z) calcd for C14H8ClNaNO2 [M + Na]+ 280.0141, found 280.0138. 4-fluoro-2-nitro-1-(phenylethynyl)benzene (3da). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3da as a yellow solid (51.4 mg, 71% yield); mp 50-52 oC; 1H NMR (400 MHz, CDCl3): δ 7.82 (d, J = 8.4 Hz, 1H), 7.74 -7.70 (m, 1H), 7.60-7.59 (m, 2H), 7.39-7.32 (m, 4H); 13C NMR (100 MHz, CDCl3): δ 161.1 (d, J = 252.7 Hz), 150.1 (d, J = 9.6 Hz), 136.1 (d, J = 7.9 Hz), 131.9, 129.3, 128.4, 122.2, 120.6 (d, J = 21.7 Hz), 115.1 (d, J = 4.0 Hz), 112.6 (d, J = 26.8 Hz), 97.0 (d, J = 1.9 Hz), 83.7;

19

F NMR (376 MHz,

CDCl3): δ -107.6; HRMS (ESI, m/z) calcd for C14H8FNaNO2 [M + Na]+ 264.0437, found 264.0444. 4-chloro-2-nitro-1-(phenylethynyl)benzene (3ea). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ea as a yellow solid (50.3 mg, 65% yield); mp 71-73 oC; 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.65 (d, J = 8.4 Hz, 1H),


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7.59-7.55 (m, 3H), 7.39-7.38 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 149.7, 135.4, 134.3, 133.0, 132.0, 129.4, 128.5, 125.0, 122.0, 117.3, 98.2, 83.9; HRMS (ESI, m/z) calcd for C14H8ClNaNO2 [M + Na]+ 280.0141, found 280.0116. 4-bromo-2-nitro-1-(phenylethynyl)benzene (3fa). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3fa as a yellow solid (55.3 mg, 61% yield); mp 79-81 oC; 1H NMR (400 MHz, CDCl3): δ 8.23 (s, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.60-7.56 (m, 3H), 7.39-7.38 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 149.7, 135.9, 135.5, 132.0, 129.5, 128.5, 127.8, 122.0, 121.8, 117.7, 98.4, 84.0; HRMS (ESI, m/z) calcd for C14H8BrNaNO2 [M + Na]+ 323.9636, found 323.9627. 4-methoxy-2-nitro-1-(phenylethynyl)benzene (3ga). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 80/1, v/v) afforded 3ga as a yellow solid (41.8 mg, 55% yield); mp 53-55 oC; 1H NMR (400 MHz, CDCl3): δ 7.62 (d, J = 8.8 Hz, 1H), 7.59 (m, 3H), 7.37 (m, 3H), 7.14 (d, J = 8.4 Hz, 1H), 3.90 (s, 3H);

13

C NMR (100 MHz, CDCl3): δ 159.4, 150.4,

135.5, 131.8, 128.8, 128.4, 122.7, 119.8, 110.9, 109.3, 95.2, 84.7, 56.0; HRMS (ESI, m/z) calcd for C15H11NaNO3 [M + Na]+ 276.0637, found 276.0636. 2-nitro-1-(phenylethynyl)-4-(trifluoromethyl)benzene

(3ha).

Purification

by

column

chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ha as a yellow solid (63.8 mg, 73% yield); mp 55-57 oC; 1H NMR (400 MHz, CDCl3): δ 8.36 (s, 1H), 7.87-7.82 (m, 2H), 7.62 (d, J = 7.2 Hz, 2H), 7.45-7.39 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 149.3, 135.3, 132.2, 130.5(q, J = 34.2 Hz), 129.9, 129.2 (q, J = 3.5 Hz), 128.6, 122.7 (q, J = 271.1 Hz), 122.4, 122.2 (q, J = 3.8 Hz), 121.7, 100.4, 83.8; 19F NMR (376 MHz, CDCl3): δ -63.0; HRMS (ESI, m/z) calcd for C15H9F3NO2 [M + H]+ 292.0585, found 292.0582.



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4-fluoro-1-nitro-2-(phenylethynyl)benzene (3ia). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ia as a light yellow solid (46.3 mg, 64% yield); mp 50-52 oC; 1H NMR (400 MHz, CDCl3): δ 8.16 (dd, J = 8.8, 5.1 Hz, 1H), 7.61 (d, J = 6.4 Hz, 2H), 7.40-7.39 (m, 4H), 7.15 (t, J = 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 164.4 (d, J = 255.6 Hz), 145.7 (d, J = 3.4 Hz), 132.1, 129.6, 128.5, 127.5 (d, J = 10.3 Hz), 121.9, 121.6 (d, J = 11.2 Hz), 121.0 (d, J = 24.6 Hz), 115.9 (d, J = 23.3 Hz), 98.6, 84.0;

19

F NMR (376 MHz,

CDCl3): δ -104.1; HRMS (ESI, m/z) calcd for C14H8FNaNO2 [M + Na]+ 264.0437, found 264.0439. 4-chloro-1-nitro-2-(phenylethynyl)benzene (3ja). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ja as a yellow solid (47.9 mg, 62% yield); mp 49-51 oC; 1H NMR (400 MHz, CDCl3): δ 8.06 (d, J = 8.8 Hz, 1H), 7.70 (s, 1H), 7.61 (d, J = 7.2 Hz, 2H), 7.43-7.39 (m, 4H); 13C NMR (100 MHz, CDCl3): δ 147.7, 139.4, 134.1, 132.1, 129.6, 128.6, 128.5, 126.1, 121.9, 120.5, 98.6, 83.8; HRMS (ESI, m/z) calcd for C14H8ClNaNO2 [M + Na]+ 280.0141, found 280.0121. 4-methyl-1-nitro-2-(phenylethynyl)benzene (3ka). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ka as a yellow liquid (41.2 mg, 58% yield); 1H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 8.4 Hz, 1H), 7.64-7.63 (m, 2H), 7.55 (s, 1H), 7.42-7.41 (m, 3H), 7.29-7.28 (m, 1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 147.3, 144.1, 134.9, 132.0, 129.3, 129.1, 128.4, 124.9, 122.5, 118.7, 96.6, 85.2, 21.2; HRMS (ESI, m/z) calcd for C15H11NaNO2 [M + Na]+ 260.0687, found 260.0682. 4-methoxy-1-nitro-2-(phenylethynyl)benzene (3la). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 80/1, v/v) afforded 3la as a orange solid (39.4 mg, 52%


Page 17 of 35 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


yield); mp 67-69 oC; 1H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 9.2 Hz, 1H), 7.62-7.60 (m, 2H), 7.38 (m, 3H), 7.14 (s, 1H), 6.92 (d, J = 6.8 Hz, 1H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 162.8, 142.6, 132.0, 129.2, 128.4, 127.2, 122.4, 121.0, 118.4, 114.6, 97.0, 85.4, 56.0; HRMS (ESI, m/z) calcd for C15H11NaNO3 [M + Na]+ 276.0637, found 276.0632. 1-methyl-3-nitro-2-(phenylethynyl)benzene (3ma). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ma as a light yellow liquid (34.2 mg, 48% yield); 1H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 8.0 Hz, 1H), 7.61-7.58 (m, 2H), 7.51 (d, J = 7.6 Hz, 1H), 7.39-7.32 (m, 4H), 2.62 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 150.5, 143.1, 133.8, 131.8, 129.2, 128.4, 127.7, 122.6, 122.0, 118.0, 101.8, 83.1, 21.3; HRMS (ESI, m/z) calcd for C15H11NaNO2 [M + Na]+ 260.0687, found 260.0688. 3-((2-nitrophenyl)ethynyl)aniline (3ab). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 8/1, v/v) afforded 3ab as a yellow solid (32.9 mg, 46% yield); mp 79-81 oC; 1H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.4 Hz, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.45 (t, J = 8.0 Hz, 1H), 7.16 (t, J = 8.0 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H), 6.92 (s, 1H), 6.71 (d, J = 8.0 Hz, 1H), 3.74 (s, 2H); 13C NMR (100 MHz, CDCl3): δ 149.6, 146.4, 134.5, 132.7, 129.4, 128.4, 124.7, 123.0, 122.3, 118.9, 118.1, 116.2, 97.5, 84.1; HRMS (ESI, m/z) calcd for C14H10NaN2O2 [M + Na]+ 261.0640, found 261.0634. 1-nitro-2-(3-tolylethynyl)benzene (3ac). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ac as a yellow liquid (49.1 mg, 69% yield); 1

H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 8.4 Hz, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.57 (t, J = 7.6

Hz, 1H), 7.45-7.37 (m, 3H), 7.24 (s, 1H), 7.17 (d, J = 7.6 Hz, 1H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3): δ149.6, 138.2, 134.5, 132.8, 132.5, 130.1, 129.1, 128.4, 128.3, 124.7, 122.1, 118.9,



Page 18 of 35

97.4, 84.4, 21.2; HRMS (ESI, m/z) calcd for C15H11NaNO2 [M + Na]+ 260.0687, found 260.0679. 1-((3-fluorophenyl)ethynyl)-2-nitrobenzene (3ad). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ad as a yellow solid (48.5 mg, 67% yield); mp 31-33 oC; 1H NMR (400 MHz, CDCl3): δ 8.04 (d, J = 8.4 Hz, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.56 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H), 7.34-7.28 (m, 2H), 7.24-7.20 (m, 1H), 7.04 (t, J = 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 162.3 (d, J = 245.5 Hz), 149.6 (d, J = 1.7 Hz), 134.6, 132.9, 130.1 (d, J = 8.6 Hz), 128.9, 127.9 (d, J = 3.1 Hz), 124.8, 124.2 (d, J = 9.5Hz), 118.7 (d, J =22.8 Hz), 118.3, 116.6 (d, J = 21.1 Hz), 95.5 (d, J = 3.6 Hz), 85.5;

19

F NMR(376 MHz,

CDCl3): δ -112.5; HRMS (ESI, m/z) calcd for C14H8FNaNO2 [M + Na]+ 264.0437, found 264.0438. 1-((4-fluorophenyl)ethynyl)-2-nitrobenzene (3ae). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ae as a yellow solid (52.8 mg, 73% yield); mp 79-81 oC; 1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.61-7.56 (m, 3H), 7.46 (t, J = 7.8 Hz, 1H), 7.07 (t, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 163.0 (d, J = 249.7 Hz), 149.5, 134.4, 134.0 (d, J=8.5 Hz), 132.8, 128.6, 124.7, 118.6, 118.5 (d, J = 3.4 Hz), 115.8 (d, J =22.1 Hz), 96.0, 84.5; 19F NMR (376 MHz, CDCl3): δ -109.1; HRMS (ESI, m/z) calcd for C14H8FNaNO2 [M + Na]+ 264.0437, found 264.0429. 1-((4-bromophenyl)ethynyl)-2-nitrobenzene (3af). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3af as a yellow solid (64.4 mg, 71% yield); mp 81-83 oC; 1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.61 (t, J = 7.6 Hz, 1H), 7.53-7.48 (m, 3H), 7.45 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 149.6, 134.5, 133.4, 132.9, 131.8, 128.8, 124.8, 123.7, 121.3, 118.4, 95.9, 85.8; HRMS


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(ESI, m/z) calcd for C14H8BrNaNO2 [M + Na]+ 323.9636, found 323.9627. 1-nitro-2-(4-tolylethynyl)benzene (3ag). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ag as a orange solid (53.4 mg, 75% yield); mp: 55-57 oC; 1H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.59 (t, J = 7.4 Hz, 1H), 7.50-7.45 (m, 3H), 7.19 (d, J = 7.2 Hz, 2H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 149.5, 139.6, 134.5, 132.7, 131.9, 129.2, 128.3, 124.7, 119.3, 119.0, 97.5, 84.3, 21.6; HRMS (ESI, m/z) calcd for C15H11NaNO2 [M + Na]+ 260.0687, found 260.0684. 1-((4-(tert-butyl)phenyl)ethynyl)-2-nitrobenzene (3ah). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 3ah as a yellow solid (67.9 mg, 81% yield); mp 84-86 oC; 1H NMR (400 MHz, CDCl3): δ 8.08 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.61-7.53 (m, 3H), 7.46-7.39 (m, 3H), 1.33 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 152.7, 149.5, 134.5, 132.7, 131.8, 128.3, 125.5, 124.7, 119.3, 119.0, 97.5, 84.2, 34.9, 31.1; HRMS (APCI, m/z) calcd for C18H18NO2 [M + H]+ 280.1338, found 280.1325. 1-((4-methoxyphenyl)ethynyl)-2-nitrobenzene (3ai). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 80/1, v/v) afforded 3ai as a dark yellow solid (63.1 mg, 83% yield); mp 74-76 oC; 1H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.60-7.53 (m, 3H), 7.43 (t, J = 7.8 Hz, 1H), 6.90 (d, J = 8.0 Hz, 2H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.4, 149.4, 134.3, 133.6, 132.7, 128.0, 124.7, 119.2, 114.4, 114.1, 97.6, 83.9, 55.3; HRMS (ESI, m/z) calcd for C15H11NaNO3 [M + Na]+ 276.0637 , found 276.0632. 1-(4-((2-nitrophenyl)ethynyl)phenyl)ethan-1-one (3aj). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 50/1 to 20/1, v/v) afforded 3aj as a yellow solid (42.2 mg, 53% yield); mp 102-104 oC; 1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 8.4 Hz, 1H), 7.94 (d,



J = 7.6 Hz, 2H), 7.72 (d, J = 8.0 Hz, 1H), 7.66-7.60 (m, 3H), 7.49 (t, J = 7.8 Hz, 1H), 2.61 (s, 3H).; 13

C NMR (100 MHz, CDCl3): δ 197.2, 149.6, 136.9, 134.6, 132.9, 132.1, 129.1, 128.2, 127.1,

124.8, 118.1, 95.8, 87.6, 26.6; MS (ESI, m/z) calcd for C16H11NO3 [M]+ 265.1, found: 265.1. 1-nitro-2-(pent-1-yn-1-yl)benzene (3ak). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 200/1 to 100/1, v/v) afforded 3ak as a light yellow liquid (35.2 mg, 62% yield); 1H NMR (400 MHz, CDCl3): δ 7.96 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 7.6 Hz, 1H), 7.51 (t, J = 7.4 Hz, 1H), 7.39 (t, J = 7.6 Hz, 1H), 2.46 (t, J = 6.6 Hz, 2H), 1.69-1.64 (m, 2H), 1.07 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 150.0, 134.8, 132.5, 127.8, 124.3, 119.3, 99.2, 76.0, 21.8, 21.7, 13.5; HRMS (ESI, m/z) calcd for C11H11NaNO2 [M + Na]+ 212.0687, found 212.0684. 1-nitro-2-(oct-1-yn-1-yl)benzene (3al). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 200/1 to 100/1, v/v) afforded 3al as a light yellow liquid (41.6 mg, 60% yield); 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 7.6 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), 7.38 (t, J = 7.8 Hz, 1H), 2.47 (t, J = 7.0 Hz, 2H), 1.67-1.59 (m, 2H), 1.51-1.43 (m, 2H), 1.34-1.31 (m, 4H), 0.90 (t, J = 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 150.1, 134.7, 132.4, 127.8, 124.3, 119.3, 99.4, 75.9, 31.3, 28.5, 28.3, 22.5, 19.8, 14.0; HRMS (ESI, m/z) calcd for C14H17NaNO2 [M + Na]+ 254.1157, found 254.1147. 1-(3,3-dimethylbut-1-yn-1-yl)-2-nitrobenzene (3am). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 200/1 to 100/1, v/v) afforded 3am as a light yellow liquid (34.7 mg, 57% yield); 1H NMR (400 MHz, CDCl3): δ 7.97 (d, J = 8.0 Hz, 1H), 7.57-7.49 (m, 2H), 7.38 (t, J = 7.6 Hz, 1H), 1.34 (s, 9H);

13

C NMR (100 MHz, CDCl3): δ 150.2, 134.5,

132.4, 127.8, 124.3, 119.3, 107.0, 74.6, 30.5, 28.4; HRMS (ESI, m/z) calcd for C12H13NaNO2 [M


Page 20 of 35

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+ Na]+ 226.0844, found 226.0849. tert-butyldimethyl((2-methyl-4-(2-nitrophenyl)but-3-yn-2-yl)oxy)silane

(3an).

Purification

by

column chromatography on silica gel (petroleum ether/ethyl acetate = 200/1 to 100/1, v/v) afforded 3an as a light yellow liquid (65.2 mg, 68% yield); 1H NMR (400 MHz, CDCl3): δ 8.02 (d, J = 8.0 Hz, 1H), 7.58-7.54 (m, 2H), 7.44 (t, J = 7.0 Hz, 1H), 1.59 (s, 6H), 0.89 (s, 9H), 0.20 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 149.8, 134.4, 132.7, 128.5, 124.5, 118.4, 102.7, 77.8, 66.9, 32.6, 25.7, 17.9, -3.0; HRMS (ESI, m/z) calcd for C17H25NaNO3Si [M + Na]+ 342.1501, found 342.1510. 1-(3-(benzyloxy)prop-1-yn-1-yl)-2-nitrobenzene (3ao). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 80/1, v/v) afforded 3ao as a light yellow liquid (43.3 mg, 54% yield); 1H NMR (400 MHz, CDCl3): δ 8.06 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 7.6 Hz, 1H), 7.58 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.43 (d, J = 7.2 Hz, 2H), 7.37 (t, J = 7.2 Hz, 2H), 7.31 (d, J = 7.0 Hz, 1H), 4.73 (s, 2H), 4.46 (s, 2H); 13C NMR (100 MHz, CDCl3): δ 149.8, 137.2, 134.9, 132.8, 128.9, 128.5, 128.3, 127.9, 124.6, 118.1, 93.4, 81.7, 71.7, 57.7; HRMS (ESI, m/z) calcd for C16H13NaNO3 [M + Na]+ 290.0793, found 290.0795. 1,4-diphenyldiacetylene (4a). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 4a as a white solid (70.4 mg, 58% yield); mp 84-86 oC; 1

H NMR (400 MHz, CDCl3): δ 7.55 (d, J = 7.2 Hz, 4H), 7.40-7.33 (m, 6H); 13C NMR (100 MHz,

CDCl3): δ 132.5, 129.2, 128.4, 121.8, 81.5, 73.9. The spectral data were in accordance with the literature.18 3,3'-(buta-1,3-diyne-1,4-diyl)dianiline (4b). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 8/1, v/v) afforded 4b as a yellow solid (72.5 mg, 52% yield); mp



118-120 oC; 1H NMR (400 MHz, CDCl3): δ 7.11 (t, J = 7.8 Hz, 2H), 6.93 (d, J = 7.6 Hz, 2H), 6.83-6.82 (m, 2H), 6.68 (dd, J = 8.0 Hz, 2.0 Hz, 2H), 3.70 (s, 4H). The spectral data were in accordance with the literature.18 1,4-di-m-tolylbuta-1,3-diyne (4c). Purification by column chromatography on silica gel (petroleum ether/ ethyl acetate = 100/1, v/v) afforded 4c as a white solid (93.9 mg, 68% yield); mp 62-64 oC; 1

H NMR (400 MHz, CDCl3): δ 7.35-7.33 (m, 4H), 7.25-7.17 (m, 4H), 2.34 (s, 6H). The spectral

data were in accordance with the literature.18 1,4-bis(3-fluorophenyl)buta-1,3-diyne (4d). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 4d as a white solid (90.0 mg, 63% yield); mp 116-118 oC; 1H NMR (400 MHz, CDCl3): δ 7.33-7.30 (m, 4H), 7.24-7.21 (m, 2H), 7.13-7.07 (m, 2H). The spectral data were in accordance with the literature.19 1,4-bis(4-fluorophenyl)buta-1,3-diyne (4e). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 4e as a white solid (87.2 mg, 61% yield); mp 182-184 oC; 1H NMR (400 MHz, CDCl3): δ 7.53-7.50 (m, 4H), 7.06-7.02 (m, 4H). The spectral data were in accordance with the literature.18 1,4-bis(4-bromophenyl)buta-1,3-diyne (4f). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 4f as a light yellow solid (127.4 mg, 59% yield); mp 251-253 oC; 1H NMR (400 MHz, CDCl3): δ 7.48 (d, J = 8.4 Hz, 4H), 7.38 (d, J = 8.4 Hz, 4H). The spectral data were in accordance with the literature.20 1,4-di-p-tolylbuta-1,3-diyne (4g). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 4g as a white solid (93.9 mg, 68% yield); mp: 175-177 o

C; 1H NMR (400 MHz, CDCl3): δ 7.43 (d, J = 8.0 Hz, 4H), 7.15 (d, J = 8.0 Hz, 4H), 2.38 (s, 6 H).


Page 22 of 35

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The spectral data were in accordance with the literature.18 1,4-bis(4-(tert-butyl)phenyl)buta-1,3-diyne (4h). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100/1, v/v) afforded 4h as a white solid (131.9 mg, 70% yield); mp 210-212 oC; 1H NMR (400 MHz, CDCl3): δ 7.47 (d, J = 8.4 Hz, 4H), 7.36 (d, J = 8.8 Hz, 4H), 1.32 (s, 18H). The spectral data were in accordance with the literature.18 1,4-bis(4-methoxyphenyl)buta-1,3-diyne (4i). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 80/1, v/v) afforded 4i as a white solid (108.5 mg, 69% yield); mp 134-136 oC; 1H NMR (400 MHz, CDCl3): δ 7.46 (d, J = 7.2 Hz, 4H), 6.85 (d, J = 7.6 Hz, 4H), 3.82 (s, 6H). The spectral data were in accordance with the literature.18 1,1'-(buta-1,3-diyne-1,4-diylbis(4,1-phenylene))bis(ethan-1-one) (4j). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 50/1 to 20/1, v/v) afforded 4j as a light yellow solid (94.4 mg, 55% yield); mp 172-174 oC; 1H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 8.4 Hz, 4H), 7.62 (d, J = 8.4 Hz, 4H), 2.61 (s, 6H). The spectral data were in accordance with the literature.21 deca-4,6-diyne (4k). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 200/1 to 100/1, v/v) afforded 4k as a colorless liquid (38.6 mg, 48% yield); 1H NMR (400 MHz, CDCl3): δ 2.22 (t, J = 7.0 Hz, 4H), 1.59-1.50 (m, 4H), 0.98 (t, J = 7.4 Hz, 6H). The spectral data were in accordance with the literature.22 hexadeca-7,9-diyne (4l). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 200/1 to 100/1, v/v) afforded 4l as a colorless liquid (82.5 mg, 63% yield); 1H NMR (400 MHz, CDCl3): δ 2.24 (t, J = 6.8 Hz, 4H), 1.55-1.47 (m, 4H), 1.41-1.25 (m, 12H), 0.88 (t, J = 6.8 Hz, 6H). The spectral data were in accordance with the literature.18



Page 24 of 35

2,2,7,7-tetramethylocta-3,5-diyne (4m). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 200/1 to 100/1, v/v) afforded 4m as a white solid (47.7 mg, 49% yield); mp 124-126 oC; 1H NMR (400 MHz, CDCl3): δ 1.22 (s, 18H). The spectral data were in accordance with the literature.18 2,2,3,3,5,5,10,10,12,12,13,13-dodecamethyl-4,11-dioxa-3,12-disilatetradeca-6,8-diyne

(4n).

Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 200/1 to 100/1, v/v) afforded 4n as a colorless liquid (146.8 mg, 62% yield); 1H NMR (400 MHz, CDCl3): δ 1.47 (s, 12H), 0.87 (s, 18H), 0.17 (s, 12H);

13

C NMR (100 MHz, CDCl3): δ 84.4, 67.2, 66.6,

32.6, 25.7, 17.9, -3.1. MS (ESI, m/z) calcd for C22H42O2Si2 [M]+ 394.3, found: 394.5. 1,6-bis(benzyloxy)hexa-2,4-diyne (4o). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 80/1, v/v) afforded 4o as a colorless liquid (111.5 mg, 64% yield); 1

H NMR (400 MHz, CDCl3): δ 7.40-7.33 (m, 10H), 4.64 (s, 4H), 4.28 (s, 4H). The spectral data

were in accordance with the literature.23 2-nitro-1,4-bis(2-phenylethynyl)benzene (5). 4-bromo-2-nitro-1-(phenylethynyl)benzene 3fa (90.6 mg, 0.3 mmol), copper (I) iodide (2.9 mg, 0.015 mmol) and bis(triphenylphosphine) palladium (II) dichloride (10.5 mg, 0.015 mmol) were added to a 25 mL Schlenk flask equipped with a high-vacuum PTFE valve-to-glass seal. The tube was evacuated and backfilled with N2 three times after which triethylamine (60.7 mg, 0.6 mmol) and THF (1 mL) were added via syringe. After 5 min at room temperature, the phenylacetylene (42.9 mg, 0.42 mmol) was added. The resulting mixture was stirred at 80 oC for 4 h. It was then cooled to room temperature, the reaction mixture was quenched with H2O (20 mL), extracted with DCM (20 mL × 3), washed with brine. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The


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residue was purified by flash chromatography (petroleum ether/ethyl acetate = 20/1, v/v) to afford the desired product. 83.4 mg, 86% yield; yellow solid; mp 85-87 oC; 1H NMR (400 MHz, CDCl3): δ 8.23 (s, 1H), 7.71-7.69 (m, 2H), 7.61-7.60 (m, 2H), 7.57-7.56 (m, 2H), 7.40-7.38 (m, 6H); 13C NMR (100 MHz, CDCl3): δ 149.4, 135.2, 134.5, 132.1, 131.8, 129.4, 129.2, 128.5, 128.4, 127.6, 124.1, 122.2, 122.1, 118.0, 98.9, 93.5, 86.9, 84.8; HRMS (APCI, m/z) calcd for C22H14NO2 [M + H]+ 324.1025, found 324.0995. 2-phenylindole (6).16 To a refluxing solution of 1-nitro-2-(phenylethynyl)benzene 3aa (66.9 mg, 0.3 mmol) and dibromoethane (563.6 mg, 3 mmol) in ethanol (3 mL) was added zinc powder (156.9 mg, 2.4 mmol) in one portion. After refluxing for 12 h, the reaction mixture was filtered and poured into water (5 mL), extracted with ether (5 mL × 3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (petroleum ether/ethyl acetate = 8/1, v/v) to afford the desired product. 45.2 mg, 78% yield; white solid; mp 189-191 oC; 1H NMR (400 MHz, CDCl3): δ 8.25 (s, 1H), 7.63-7.61 (m, 3H), 7.41 (t, J = 7.2 Hz, 2H), 7.35 (d, J = 8.0 Hz, 1H), 7.30 (t, J = 7.4 Hz, 1H), 7.18 (t, J = 7.6 Hz, 1H), 7.12 (t, J = 7.2 Hz, 1H), 6.81 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 137.8, 136.8, 132.3, 129.2, 129.0, 127.7, 125.1, 122.3, 120.6, 120.2, 110.9, 99.9; HRMS (ESI, m/z) calcd for C14H12N [M + H]+ 194.0970, found 194.0966. Control experiments (Scheme 3, eq 11). Anhydrous CuSO4 (9.6 mg, 0.06 mmol), 1,10-phenanthroline (21.6 mg, 0.12 mmol), 2-nitrobenzoic acid (50.1 mg, 0.3 mmol), NaHCO3 (50.4 mg, 0.6 mmol) and 4 Å MS (50 mg) were added to a 25 mL Schlenk flask equipped with a high-vacuum PTFE valve-to-glass seal. The tube was evacuated and backfilled with O2 three times after which freshly distillated toluene (1.5 mL) and DMF (0.5 mL) were added via syringe. The



resulting mixture was stirred at 150 oC for 24 h. It was then cooled to room temperature, the reaction mixture was quenched with H2O (20 mL), extracted with ethyl acetate (20 mL × 3), washed with brine. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (petroleum ether/ethyl acetate = 20/1, v/v) to yield the nitrobenzene 7 in 22% yield (8.1 mg) and 2,2'-dinitro-1,1'-biphenyl 8 in 37% yield (13.5 mg). Nitrobenzene (7). 8.1 mg, 22% yield; light yellow liquid; 1H NMR (400 MHz, CDCl3): δ 8.24 (d, J = 7.6 Hz, 2H), 7.70 (t, J = 7.2 Hz, 1H), 7.55 (t, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 148.2, 134.5, 129.3, 123.5. The spectral data were in accordance with the literature.24 2,2'-dinitro-1,1'-biphenyl (8). 13.5 mg, 37% yield; yellow solid; mp 120-122 oC; 1H NMR (400 MHz, CDCl3): δ 8.22 (d, J = 8.0 Hz, 2H), 7.69 (t, J = 7.6 Hz, 2H), 7.60 (t, J = 8.0 Hz, 2H), 7.30 (d, J = 7.6 Hz, 2H);

13

C NMR (100 MHz, CDCl3): δ 147.2, 134.2, 133.4, 130.9, 129.1, 124.8. The

spectral data were in accordance with the literature.25 Control experiments (Scheme 3, eq 12). Anhydrous CuSO4 (9.6 mg, 0.06 mmol), 1,10-phenanthroline (21.6 mg, 0.12 mmol), NaHCO3 (50.4 mg, 0.6 mmol) and 4 Å MS (50 mg) were added to a 25 mL Schlenk flask equipped with a high-vacuum PTFE valve-to-glass seal. The tube was evacuated and backfilled with O2 three times after which phenylacetylene (30.7 mg, 0.3 mmol), freshly distillated toluene (1.5 mL) and DMF (0.5 mL) were added via syringe. The resulting mixture was stirred at 150 oC for 24 h. It was then cooled to room temperature, the reaction mixture was quenched with H2O (20 mL), extracted with ethyl acetate (20 mL × 3), washed with brine. The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (petroleum ether/ethyl acetate


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=100/1, v/v) to yield the 1,4-diphenyldiacetylene 4a in 42% yield (12.8 mg). Control experiments (Scheme 3, eq 13). Anhydrous CuSO4 (9.6 mg, 0.06 mmol), 1,10-phenanthroline (21.6 mg, 0.12 mmol), nitrobenzene 7 (36.9 mg, 0.3 mmol) or 2, 2'-dinitro-1, 1'-biphenyl 8 (73.2 mg, 0.3 mmol), NaHCO3 (50.4 mg, 0.6 mmol) and 4 Å MS (50 mg) were added to a 25 mL Schlenk flask equipped with a high-vacuum PTFE valve-to-glass seal. The tube was evacuated and backfilled with O2 three times after which phenylacetylene (122.6 mg, 1.2 mmol), freshly distillated toluene (1.5 mL) and DMF (0.5 mL) were added via syringe. The resulting mixture was stirred at 150 oC for 24 h. It was then cooled to room temperature, TLC analysis showed no desired product 3aa was formed. Control experiments (Scheme 3, eq 14). Anhydrous CuSO4 (9.6 mg, 0.06 mmol), 1,10-phenanthroline (21.6 mg, 0.12 mmol), 2-nitrobenzoic acid (50.1 mg, 0.3 mmol), 1,4-diphenylbuta-1,3-diyne (60.7 mg, 0.3 mmol), NaHCO3 (50.4 mg, 0.6 mmol) and 4 Å MS (50 mg) were added to a 25 mL Schlenk flask equipped with a high-vacuum PTFE valve-to-glass seal. The tube was evacuated and backfilled with O2 three times after which freshly distillated toluene (1.5 mL) and DMF (0.5 mL) were added via syringe. The resulting mixture was stirred at 150 oC for 24 h. It was then cooled to room temperature, TLC analysis showed no desired product 3aa was formed. Supporting Information: Table S1, Chart S1 and copies of 1H,

13

C and

19

F NMR spectra of

compounds 3aa-3ma, 3ab-3ao, 4a-4o and 5-8. This material is available free of charge via the Internet at http://pubs.acs.org. REFERENCES (1) (a) Diederich, F.; Stang, P. J.; Tykwinski, R. R. Acetylene Chemistry: Chemistry, Biology, and



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N-Hydroxyphthalimide

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of Substituted Benzoic Acids with Phenylboronic Acids. Synth. Commun. 2014, 44, 289. (c) Hu, L.; Wang, D.; Chen, X.; Yu, L.; Yu, Y.; Tan, Z.; Zhu, G. Copper-Catalyzed Decarboxylative Methylthiolation of Aromatic Carboxylate Salts with DMSO. Org. Biomol. Chem. 2017, 15, 5674. (13) During the preparation of this manuscript, Su reported the Pd-catalyzed decarboxylative Sonogashira reaction between aryl carboxylic acids and terminal alkynes via decarboxylative bromination using NBS as the bromide source. Jiang, Q.; Li, H.; Zhang, X.; Xu, B.; Su, W. Pd-Catalyzed Decarboxylative Sonogashira Reaction via Decarboxylative Bromination. Org. Lett. 2018, 20, 2424. (14) Similar limitations have been observed in other Copper-catalyzed decarboxylative cross-couplings (see ref. 10a, 10d and 10e). (15) Xue, L.; Su, W.; Lin, Z. Mechanism of Silver- and Copper-Catalyzed Decarboxylation Reactions of Aryl Carboxylic Acids. Dalton Trans. 2011, 40, 11926. (16) Okuma, K.; Seto, J.-i.; Sakaguchi, K.-i.; Ozaki, S.; Nagahora, N.; Shioji, K. Palladium-free Zinc-Mediated Hydroamination of Alkynes: Efficient Synthesis of Indoles from 2-Akynylaniline Derivatives. Tetrahedron Lett. 2009, 50, 2943. (17) (a) King, A. E.; Huffman, L. M.; Casitas, A.; Costas, M.; Ribas, X.; Stahl, S. S. Copper-Catalyzed Aerobic Oxidative Functionalization of an Arene C–H Bond: Evidence for an Aryl-Copper(III) Intermediate. J. Am. Chem. Soc. 2010, 132, 12068. (b) Wendlandt, A. E.; Suess, A. M.; Stahl, S. S. Copper-Catalyzed Aerobic Oxidative C–H Functionalizations: Trends and Mechanistic Insights. Angew. Chem., Int. Ed. 2011, 50, 11062. (c) Suess, A. M.; Ertem, M. Z.; Cramer, C. J.; Stahl, S. S. Divergence between Organometallic and



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Single-Electron-Transfer Mechanisms in Copper(II)-Mediated Aerobic C−H Oxidation. J. Am. Chem. Soc. 2013, 135, 9797. (d) Hoover, J. M. Mechanistic Aspects of Copper-Catalyzed Decarboxylative Coupling Reactions of (Hetero)aryl Carboxylic Acids. Comments Inorg. Chem. 2017, 37, 169. (e) Baur, A.; Bustin, K. A.; Aguilera, E.; Petersen, J. L.; Hoover, J. M. Copper and Silver Benzoate and Aryl Complexes and Their Implications for Oxidative Decarboxylative Coupling Reactions. Org. Chem. Front. 2017, 4, 519. (18) Cheng, G.; Zhang, H.; Cui, X. Copper(I)-Catalyzed Homo-coupling of Terminal Alkynes at Room Temperature under Solvent and Base Free Conditions using O2 as An Oxidant. RSC Adv. 2014, 4, 1849. (19) Xu, D.; Sun, Q.; Quan, Z.; Wang, X.; Sun, W. Cobalt-Catalyzed Dimerization and Homocoupling of Terminal Alkynes. Asian J. Org. Chem. 2018, 7, 155. (20) Chen, L.; Lemma, B. E.; Rich, J. S.; Mack, J. Freedom: A Copper-Free, Oxidant-Free and Solvent-Free Palladium Catalysed Homocoupling Reaction. Green Chem. 2014, 16, 1101. (21) Liu, D.; Li, F.; Li, H.; Gong, W.; Gao, J.; Lang, J. Efficient and Reusable CuI/1,10-Phenanthroline-Catalyzed

Oxidative

Decarboxylative

Homocoupling

of

Arylpropiolic Acids in Aqueous DMF. Eur. J. Org. Chem. 2014, 22, 4817. (22) Ötvös, S. B.; Georgiádes, Á.; Mészáros, R.; Kis, K.; Pálinkó, I.; Fülöp, F. Continuous-ﬂow Oxidative Homocouplings without Auxiliary Substances: Exploiting A Solid Base Catalyst. J. Catal. 2017, 348, 90. (23) Yin, W.; He, C.; Chen, M.; Zhang, H.; Lei, A. Nickel-Catalyzed Oxidative Coupling Reactions of Two Different Terminal Alkynes Using O2 as the Oxidant at Room Temperature: Facile Syntheses of Unsymmetric 1,3-Diynes. Org. Lett. 2009, 11, 709.


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(24) Seo, S.; Taylor, J. B.; Greaney, M. F. Protodecarboxylation of Benzoic Acids under Radical Conditions. Chem. Commun. 2012, 48, 8270. (25) Cornella, J.; Lahlali, H.; Larrosa, I. Decarboxylative Homocoupling of (Hetero)aromatic Carboxylic Acids. Chem. Commun. 2010, 46, 8276.


Synthesis of Aryl Alkynes via Copper Catalyzed Decarboxylative

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