octa-1,7-diyne

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oct-1,7-diyne (6.3 g, 59.3 mmol) was alkylated with 2-(7-bromoheptyloxy)tetrahydro-2H-pyran (11 g, 39.56 mmol) as described above to give 2-(pentadeca-8,14-diynyloxy)tetrahydro-2H-pyran (7.82 g, 64%) as a colorless oil. TLC: 10% EtOAc/hexanes, Rf≈0.6; 1H NMR (400 MHz, CDCl3) δ 4.57 (t, J=2.5 Hz, 1H), 3.82-3.87 (m, 1H), 3.70-3.77 (m, 1H), 3.46-3.51 (m, 1H), 3.36-3.42 (m, 1H), 2.14-2.20 (m, 6H), 1.93 (t, J=2.6 Hz, 1H), 1.46-1.72 (m, 20 H)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oct-1,7-diyne (9.0 g, 84.9 mmol; G F Smith) was alkylated with 2-(4-bromobutoxy)-tetrahydropyran (15 g, 63.68 mmol) as described above for the synthesis of 2-(pentadeca-5,14-diynyloxy)tetrahydropyran to give 2-(dodeca-5,11-diynyloxy)tetrahydropyran (10.85 g, 65%) as a colorless oil. TLC: 10% EtOAc/hexanes, Rf≈0.6; 1H NMR (400 MHz, CDCl3) δ 4.57 (t, J=2.5 Hz, 1H), 3.82-3.87 (m, 1H), 3.70-3.77 (m, 1H), 3.46-3.51 (m, 1H), 3.36-3.42 (m, 1H), 2.14-2.20 (m, 6H), 1.93 (t, 1H, J=2.5 Hz), 1.46-1.72 (m, 14 H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oct-1,7-diyne (9.0 g, 84.9 mmol; G F Smith) was alkylated with 2-(4-bromobutoxy)-tetrahydropyran (15 g, 63.68 mmol) as described above for the synthesis of 2-(pentadeca-5,14-diynyloxy)tetrahydropyran to give 2-(dodeca-5,11-diynyloxy)tetrahydropyran (10.85 g, 65%) as a colorless oil. TLC: 10% EtOAc/hexanes, Rf≈0.6; 1H NMR (400 MHz, CDCl3) δ 4.57 (t, J=2.5 Hz, 1H), 3.82-3.87 (m, 1H), 3.70-3.77 (m, 1H), 3.46-3.51 (m, 1H), 3.36-3.42 (m, 1H), 2.14-2.20 (m, 6H), 1.93 (t, 1H, J=2.5 Hz), 1.46-1.72 (m, 14 H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1,7-octadiyne (254.4 mg, 2.4 mmol) in dry THF (50 mL) cooled at −78° C. was added nBuLi (1.6 M in hexanes, 1.5 mL, 2.0 mmol) followed by stirring at the same temperature for 10 minutes. To the previously prepared lithium acetylide solution was added a solution of α-bromocinnamaldehyde Compound 1 (422.0 mg, 2.0 mmol) in dry THF (5 mL) and the resultant mixture was stirred at −78° C. for 15 minutes. The reaction was then quenched with saturated aqueous NH4Cl (20 mL) and extracted with EtOAc (50 mL×2). The combined organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 14 percent EtOAc in hexane) to give 613.1 mg (97 percent) of Compound 7: pale yellow oil; Rf=0.33 (14 percent EtOAc in hexane); IR (neat) 3397 (br), 3294, 2944, 2864, 2232, 2116, 1492, 1430, 1064 cm−1; 1H NMR (300 MHz, CDCl3) δ7.65-7.61 (m, 2H), 7.40-7.29 (m, 3H), 7.24 (s, 1H), 5.07 (br s, 1H), 2.68 (d, J=6.18 Hz, 1H, exchangeable with D2O), 2.34-2.27 (m, 2H), 2.26-2.19 (m, 2H), 1.96 (t, J=2.67 Hz, 1H), 1.74-1.62 (m, 4H); 13C NMR (75 MHz, CDCl3) δ135.4, 129.8, 129.1, 128.9, 126.8, 88.3, 84.8, 79.0, 69.4, 69.3, 61.2, 28.1, 27.9, 19.0, 18.6; MS (+CI) m/z (relative intensity) 318 (M+, 81Br, 4), 316 (M+, 79Br, 4), 220 (100). The reaction was then quenched with saturated aqueous NH4Cl (20 mL) extracted with EtOAc (50 mL×2) The combined organic layer was washed with brine dried over anhydrous MgSO4 filtered concentrated under reduced pressure The residue was purified by flash column chromatography (silica gel, 14 percent EtOAc in hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Pd(PPh3)4 (0.55 g, 0.24 mmol) and α-bromocinnamaldehyde Compound 1 (2.08 g, 4.74 mmol) in degassed THF (170 mL) cooled in an ice-water bath was added a solution of 1,7-octadiyne (2.23 g, 9.48 mmol), triethylamine (15 mL), and CuI (0.36 g, 0.95 mmol) in degassed THF (30 mL) via a syringe under a nitrogen atmosphere. The reaction flask was then covered by a sheet of aluminum foil. After stirring at room temperature for 8 hours the reaction was quenched with saturated aqueous NH4Cl (50 mL) and diluted with EtOAc (100 mL). The organic layer was washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, 10 percent EtOAc in hexane) to give 2.13 g (91 percent) of Compound 2: yellow oil; Rf=0.50 (15 percent EtOAc in hexane); IR (neat) 3294, 2944, 2230, 2116, 1692, 1598, 1450, 1324, 1180 cm−1; 1H NMR (300 MHz, CDCl3) δ9.56 (s, 1H), 8.11-8.07 (m, 2H), 7.48-7.43 (m, 3H), 7.43 (s, 1H), 2.60 (t, J=6.65 Hz, 2H), 2.27 (td, J=6.78, 2.64 Hz, 2H), 1.97 (t, J=2.64 Hz, 1H), 1.86-1.69 (m, 4H); 13C NMR (75 MHz, CDCl3) δ192.4, 151.8, 134.9, 132.0, 131.1, 129.4, 124.1, 103.4, 84.6, 75.4, 69.4, 28.2, 28.0, 20.3, 18.7; MS (+FAB) m/z (relative intensity) 237 (M+H+, 100). was quenched with saturated aqueous NH4Cl (50 mL) diluted with EtOAc (100 mL) The organic layer was washed with brine dried over anhydrous MgSO4 filtered concentrated in vacuo The residue was purified by flash column chromatography (silica gel, 10 percent EtOAc in hexane)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,7-octadiyne (4.00 ml, 30.1 mmol) and ethyl cyanoformate (2.95 ml, 30.1 mmol) in dry degassed 1,4-dioxane (500 ml) under argon at rt was treated with cyclopentadienyl-Cobalt(I)-dicarbonyl (0.814 g, 4.52 mmol) and then heated at reflux for 18 h. Reaction was then evaporated, treated with toluene (100 ml), re-evaporated, dissolved in DCM (100 ml), filtered through a short pad of Kieselguhr, eluting with DCM, organic extracts evaporated, chromatographed (0-100% DCM:40-60 Petroleum ether then 0-10% methanol/DCM) to give product as an impure brown oil (1.27 g, 21%). degassed 1,4-dioxane (500 ml) under argon at rt heated at reflux for 18 h Reaction was then evaporated treated with toluene (100 ml) re-evaporated dissolved in DCM (100 ml) filtered through a short pad of Kieselguhr eluting with DCM, organic extracts evaporated chromatographed (0-100% DCM

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2.12 g of commercially available 1,7 octadiyne (20.0 mmol) was first combined with 80 mL of Et2O and 30 mL of THF. The solution was cooled to -78° C. and treated with 15.6 mL (42 mmol, 2.7M) of BuLi. After 0.5 hr at this temperature, 4.8 g of paraformaldehyde (160 mmol) was added and stirred for a further 2.0 hr at 0° C. At 10% soln. of aqueous HCl was added and the crude product extracted into diethyl ether. Treatment of the ether extracts with sat. NaHCO3 and brine, followed by solvent removal and column chromatography (60:40 EtOAc: Hexane) gave pure deca-2,8-diyne-1,10-diol in 50% yield. the crude product extracted into diethyl ether followed by solvent removal and column chromatography (60:40 EtOAc: Hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oct-1,7-diyne (6.3 g, 59.3 mmol) was alkylated with 2-(7-bromoheptyloxy)tetrahydro-2H-pyran (11 g, 39.56 mmol) as described above to give 2-(pentadeca-8,14-diynyloxy)tetrahydro-2H-pyran (7.82 g, 64%) as a colorless oil. TLC: 10% EtOAc/hexanes, Rf≈0.6; 1H NMR (400 MHz, CDCl3) δ 4.57 (t, J=2.5 Hz, 1H), 3.82-3.87 (m, 1H), 3.70-3.77 (m, 1H), 3.46-3.51 (m, 1H), 3.36-3.42 (m, 1H), 2.14-2.20 (m, 6H), 1.93 (t, J=2.6 Hz, 1H), 1.46-1.72 (m, 20 H)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oct-1,7-diyne (9.0 g, 84.9 mmol; G F Smith) was alkylated with 2-(4-bromobutoxy)-tetrahydropyran (15 g, 63.68 mmol) as described above for the synthesis of 2-(pentadeca-5,14-diynyloxy)tetrahydropyran to give 2-(dodeca-5,11-diynyloxy)tetrahydropyran (10.85 g, 65%) as a colorless oil. TLC: 10% EtOAc/hexanes, Rf≈0.6; 1H NMR (400 MHz, CDCl3) δ 4.57 (t, J=2.5 Hz, 1H), 3.82-3.87 (m, 1H), 3.70-3.77 (m, 1H), 3.46-3.51 (m, 1H), 3.36-3.42 (m, 1H), 2.14-2.20 (m, 6H), 1.93 (t, 1H, J=2.5 Hz), 1.46-1.72 (m, 14 H).