Compound 5

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InChIKey KUNVJBLCNBGTDK-UHFFFAOYSA-N

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

The bromination of 4 was carried out according to literature procedure (Kim, S., Kim, S., Lee, T., Ko, H. & Kim, D. A new, iterative strategy for the synthesis of unsymmetrical polyynes: Application to the total synthesis of 15,16-dihydrominquartynoic acid. Org. Lett. 6, 3601-3604, (2004)): 4-Tritylphenyl 10-(trimethylsilyl)deca­5,7,9-triynoate 4 (2.00 g, 3.63 mmol) was dissolved in dry MeCN (15 mL) and dry DCM (15 mL), the flask was shielded from light with aluminum foil, and N-bromosuccinimide (679 mg, 3.81 mmol) as well as AgNO₃ (484 mg, 3.81 mmol) were added. The resulting mixture was stirred for 8 h after which it was diluted with DCM, washed six times with 1 m HCl, and once with saturated NaCl solution. The organic phase was dried over Na₂SO₄, and concentrated in vacuo to approximately 10 mL thoroughly shielding it from light. For synthetic purposes, toluene was added, and the mixture was concentrated in vacuo. For analytic purposes, CDCl₃ (10 mL) was added, and the mixture was concentrated in vacuo. ¹H NMR (400 MHz, CDCl₃): δ = 7.30-7.20 (m, 17H), 7.02-6.98 (m, 2H), 2.71 (t, J = 7.3 Hz, 2H), 2.48 (t, J = 6.9 Hz, 2H), 2.00 (tt, J = 7.1 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃): δ = 171.2, 148.5, 146.6, 144.5, 132.2, 130.1, 127.6, 126.1, 120.4, 78.3, 66.4, 66.1, 64.7, 60.8, 59.6, 53.6, 39.9, 33.0, 23.1, 18.8. HRMS (MALDI): calcd for C₃₅H₂₅BrNaO₂: 581.0927 ([M+Na]⁺); found: 581.0914. R_f: 0.34 (DCM/n-heptane 1:1).

The Negishi coupling was carried out according to a modified literature procedure (Hoheisel, T. N. & Frauenrath, H. A convenient Negishi protocol for the synthesis of glycosylated oligo(ethynylene)s. Org. Lett. 10, 4525-4528, (2008)): MeLi · LiBr complex (3.22 mL, 2.2 m in Et₂O, 7.08 mmol) was added to 1-trimethylsilyloctadeca-1,3,5-triyne 7 (2.28 g, 7.26 mmol) in THF (20 mL) at 0 °C, and the resulting mixture was stirred for 45 min. Then ZnCl₂ (10.37 mL, 0.7 m in THF, 7.26 mmol) was added at 0 °C, and the resulting mixture was again stirred for 45 min. In a second flask, n-butyl lithium (0.29 mL, 2.5 m in n-hexane, 0.73 mmol) was added to a suspension of PdCl₂(dppf) · DCM (296 mg, 0.36 mmol) in toluene (100 mL) at 0 °C. The cooling bath was removed, the mixture was stirred for 10 min to give an orange suspension, which was again cooled to 0 °C. The toluene solution containing the 4-tritylphenyl 10-bromodeca-5,7,9-triynoate (10 mL, 3.63 mmol) and the zinc acetylide solution were simultaneously added at this temperature, and the flask was shielded from light with aluminum foil. After 48 h, the mixture was diluted with Et₂O, washed three times with saturated NH₄Cl solution, and once with saturated NaCl solution. The organic phase was dried over Na₂SO₄, and concentrated in vacuo. Column chromatography (silica gel; DCM/n-heptane 1:1) yielded 5 (0.60 g, 23%) as a brown solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.28-7.17 (m, 17H), 7.00-6.97 (m, 2H), 2.69 (t, J = 7.3 Hz, 2H), 2.50 (t, J = 6.8 Hz, 2H), 2.33 (t, J = 7.2 Hz, 2H), 1.99 (p, J = 7.0 Hz, 2H), 1.59-1.52 (m, 2H), 1.45-1.19 (m, 20H), 0.89 (t, J = 6.9 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃): δ = 171.2, 148.6, 146.7, 144.6, 132.3, 131.2, 127.7, 126.2, 120.4, 82.2, 80.1, 66.8, 65.8, 64.7, 63.0, 62.8, 62.5, 62.3, 62.0, 61.5, 61.1, 60.4, 33.0, 32.1, 29.8, 29.8, 29.7, 29.5, 29.5, 29.1, 29.0, 28.0, 23.1, 22.8, 19.7, 19.1, 14.3. HRMS (APPI): calcd for C₅₃H₅₀O₂: 718.3805 ([M]⁺); found: 718.3800. R_f: 0.43 (DCM/n-heptane 1:1).