Full Paper
doi.org/10.1002/chem.202005207
Chemistry—A European Journal
7.00 (m, HAr, 2H), 6.84 (td, J=7.6, 1.5, HAr, 1H), 6.81–6.76 (m, HAr,
2H), 3.02 (s, HAlkyne, 1H), 2.71 (s, HAlkyne, 1H), 1.60–1.47 (m, 3 CH2,
6H), 1.45–1.36 (m, CH2, 2H), 1.11 (d, J=7.3, 2 CH3, 6H), 1.08 (d,
J=7.3, 2 CH3, 6H), 1.03 (d, J=7.3, 2 CH3, 6H), 1.02 (d, J=7.3,
2 CH3, 6H), 0.97–0.85 (m, 4 CH, 4H), 0.60–0.50 ppm (m, 2 CH2,
4H). 13C NMR (126 MHz, C6D6): d=142.9 (1C, CAr), 142.7 (1C, CAr),
141.0 (1C, CAr), 140.3 (1C, CAr), 135.8 (1C, CAr), 135.6 (1C, CAr), 135.0
(1C, CAr), 133.4 (1C, CAr), 133.3 (1C, CAr), 133.0 (1C, CAr), 132.9 (1C,
CAr), 132.4 (1C, CAr), 132.1 (1C, CAr), 131.9 (1C, CAr), 131.4 (1C, CAr),
131.1 (1C, CAr), 130.5 (1C, CAr), 130.5 (1C, CAr), 129.8 (1C, CAr), 129.7
(1C, CAr), 129.2 (1C, CAr), 128.8 (1C, CAr), 128.7 (1C, CAr), 128.6 (1C,
CAr), 127.2 (1C, CAr), 126.6 (1C, CAr), 126.0 (1C, CAr) 125.2 (1C, CAr),
124.1 (1C, CAr) 123.8 (1C, CAr), 123.6 (1C, CAr), 123.3 (1C, CAr), 121.9
(1C, CAr), 121.5 (1C, CAr), 119.4 (1C, CN), 119.3 (1C, CN), 106.9 (1C,
Calkyne), 106.8 (1C, Calkyne), 94.5 (1C, Calkyne), 94.3 (1C, Calkyne), 94.1 (1C,
Calkyne), 92.6 (1C, Calkyne), 92.6 (1C, Calkyne), 90.9 (1C, Calkyne), 90.4 (1C,
Calkyne), 89.1 (1C, Calkyne), 84.0 (1C, Calkyne), 83.0 (1C, Calkyne), 81.9 (1C,
Calkyne), 78.6 (1C, Calkyne), 21.6 (1C, CH2), 21.4 (1C, CH2), 20.4 (1C, CH2),
20.4 (1C, CH2), 18.5 (2C, CH3), 18.4 (2C, CH3), 18.2 (2C, CH3), 18.2
(2C, CH3), 12.1 (2C, CH), 12.0 (2C, CH), 9.7 (1C, CH2), 9.6 ppm (1C,
CH2). The peaks of 127.9 and 128.3 are only visible in the DEPT-135
experiment, as the signals are overlain by C6D6. HR-MS (ESI, MeOH)
calcd For C70H64N2NaSi2+: [M+Na]+, 1011.4500; found [M+Na]+,
1011.4489.
(1C, CAr), 145.0 (1C, CAr), 144.1 (1C, CAr), 141.5 (1C, CAr), 141.0 (1C,
CAr), 134.7 (1C, CAr), 133.5 (1C, CAr), 132.9 (1C, CAr), 132.5 (1C, CAr),
132.0 (1C, CAr), 131.6 (1C, CAr), 131.6 (1C, CAr), 131.0 (1C, CAr), 130.6
(1C, CAr), 130.4 (1C, CAr), 130.2 (1C, CAr), 129.8 (1C, CAr), 129.5 (1C,
CAr), 129.2 (1C, CAr), 129.0 (1C, CAr), 128.8 (1C, CAr), 128.6 (1C, CAr),
128.5 (1C, CAr), 128.0 (1C, CAr), 127.3 (1C, CAr), 126.9 (1C, CAr), 125.9
(1C, CAr), 125.6 (1C, CAr), 124.8 (1C, CAr), 124.0 (1C, CAr), 123.5 (1C,
CAr), 123.0 (1C, CAr), 122.9 (1C, CAr), 121.7 (1C, CAr), 119.4 (1C, CN),
119.3 (1C, CN), 106.9 (1C, Calkyne), 106.9 (1C, Calkyne), 95.1 (1C, Calkyne),
95.0 (1C, Calkyne), 94.4 (1C, Calkyne), 94.2 (1C, Calkyne), 94.1 (1C, Calkyne),
93.3 (1C, Calkyne), 90.9 (1C, Calkyne), 90.0 (1C, Calkyne), 88.9 (1C, Calkyne),
87.1 (1C, Calkyne), 82.1 (1C, Calkyne), 79.0 (1C, Calkyne), 21.6 (1C, CH2),
21.4 (1C, CH2), 20.4 (1C, CH2), 20.4 (1C, CH2), 18.5 (2C, CH3), 18.4
(2C, CH3), 18.2 (2C, CH3), 18.1 (2C, CH3), 12.1 (2C, CH), 12.0 (2C, CH),
9.6 (1C, CH2), 9.6 ppm (1C, CH2). The peaks of 128.1 and 128.2 are
only visible in the DEPT-135 experiment, as the signals are overlain
by C6D6. HR-MS (ESI, MeOH) calcd for C70H62N2NaSi2+: [M+Na]+,
1009.4344; found [M+Na]+, 1009.4335.
Macrocycle 40: A two-neck round-bottom flask was cleaned by
the following treatment to remove all copper-ions from previous
reactions. The flask was filled with conc. H2SO4 and sonicated for
10 min, followed by washing with H2O, NaOH (1m), H2O, and ace-
tone. The flask was dried in the heating oven overnight and flush-
ed with argon. To a solution of 39 (150 mg, 152 mmol, 1.0 equiv) in
THF (70 mL) was added TBAF (1m in THF, 304 mL, 304 mmol,
2.0 equiv) and the reaction mixture stirred at room temperature for
30 min. under argon. The reaction was diluted by the addition of
water (150 mL), and the aqueous phase was extracted with CH2Cl2
(250 mL). The organic layer was washed with water (150 mL) and
brine (150 mL) and dried over Na2SO4. The organic phase was con-
centrated under reduced pressure and subjected to column chro-
matography (100 g SiO2, Cy:EtOAc 98:2!86:14). Compound 40
(25 mg, 40.0 mmol, 26%) was obtained as a yellow oil. Rf =0.27 (Cy/
Macrocycle 39: CuCl, Cu(OAc)2, and pyridine were purified accord-
ing to a protocol by Scott et al.[21,31,32] Cu(OAc)2·H2O (10 g) was
dried by refluxing in Ac2O (50 mL) overnight, the salt was filtered
under N2 and washed with anhydrous THF and dried under
vacuum. CuCl (15 g) was washed with HCl aq. (1m, until the green
color disappeared), H2O, EtOH, and THF are activated by heating
under reduced pressure (1708C, 14 h, 0.1 mbar). Pyridine (600 mL)
was refluxed over CaH2 for 18 h before distillation. A 1 L round
bottom flask with baffles was filled with pyridine (470 mL) and
purged with vacuum and argon cycles in the sonicator for 15 min.
CuCl (253 mg, 2.48 mmol, 15 equiv.) and Cu(OAc)2 (629 mg,
3.47 mmol, 21 equiv.) were added in one portion (dark green solu-
tion), and the solution was purged again with vacuum and argon
cycles in the sonicator for other 10 min. To this mixture, a solution
of 38 (163 mg, 165 mmol, 1.0 equiv) in pyridine (18 mL, 5.6 cm) was
added with a syringe-pump over 9.5 h (with 0.1 mmminÀ1). One
hour after full addition, the reaction was completed according to
TLC (1 mL reaction mixture was evaporated and mixed with HCl
1m (1 mL) and EtOAc (1 mL)). The pyridine was removed under re-
duced pressure, and the green residue was dissolved in DCM
(200 mL). The yellow organic phase was washed with HCl (1m,
200 mL, light blue) and brine (100 mL), dried over Na2SO4. The or-
ganic phase was concentrated under reduced pressure and sub-
jected to column chromatography (100 g SiO2, Cy:EtOAc 97:3!
72:28). Compound 39 (153 mg, 155 mmol, 94%) was obtained as a
yellow glassy solid. Rf =0.28 (Cy/EtOAc, 5:1). 1H NMR (500 MHz,
C6D6): d=8.10 (t, J=1.6, HAr, 1H), 7.89 (ddd, J=7.8, 1.9, 1.1, HAr,
1H), 7.62 (dd, J=1.7, 0.6, HAr, 1H), 7.55 (dt, J=7.7, 1.3, HAr, 1H),
7.51–7.48 (m, HAr, 1H), 7.46 (dt, J=8.1, 1.0, HAr, 1H), 7.45 (d, J=2.0,
HAr, 1H), 7.40 (ddd, J=7.8, 1.4, 0.6, HAr, 1H), 7.37 (dd, J=8.0, 1.9,
HAr, 1H), 7.23 (t, J=7.8, HAr, 1H), 7.20–7.17 (m, HAr, 1H), 7.09 (d, J=
8.0, HAr, 1H), 7.07–7.05 (m, HAr, 1H), 7.04–6.99 (m, HAr, 3H), 6.96 (dd,
J=8.1, 1.6, HAr, 1H), 6.90 (td, J=7.6, 1.4, HAr, 1H), 6.85 (dd, J=8.0,
0.6, HAr, 1H), 6.82 (td, J=7.6, 1.3, HAr, 1H), 6.76 (ddd, J=7.8, 1.8,
1.0, HAr, 1H), 6.62 (td, J=7.7, 0.6, HAr, 1H), 1.59–1.46 (m, 3x CH2,
6H), 1.44–1.36 (m, CH2, 2H), 1.11 (d, J=7.3, 2 CH3, 6H), 1.08 (d,
J=7.3, 2 CH3, 6H), 1.05 (d, J=7.3, 2 x CH3, 6H), 1.02 (d, J=7.3,
2 CH3, 6H), 0.99–0.86 (m, 4 CH, 4H), 0.63–0.57 (m, CH2, 2H),
0.57–0.51 ppm (m, CH2, 2H). 13C NMR (126 MHz, C6D6): d=146.4
1
EtOAc, 10:1). H NMR (500 MHz, C6D6): d=8.15 (t, J=1.8, HAr, 1H),
7.77 (ddd, J=7.8, 1.8, 1.1, HAr, 1H), 7.53–7.48 (m, HAr, 3H), 7.46–7.43
(m, HAr, 2H), 7.39–7.33 (m, HAr, 2H), 7.15–7.14 (m, HAr, 1H), 7.11 (t,
J=7.7, HAr, 1H), 7.05–6.98 (m, HAr, 5H), 6.88–6.83 (m, HAr, 2H), 6.80–
6.75 (m, HAr, 2H), 6.73 (dd, J=8.0, 0.5, HAr, 1H), 6.65–6.60 (m, HAr,
1H), 2.99 (s, Halkyne, 1H), 2.65 ppm (s, Halkyne, 1H). 13C NMR (126 MHz,
C6D6): d=146.1 (1C, CAr), 144.6 (1C, CAr), 144.0 (1C, CAr), 140.9 (1C,
CAr), 140.5 (1C, CAr), 134.2 (1C, CAr), 133.2 (1C, CAr), 132.4 (1C, CAr),
131.9 (1C, CAr), 131.6 (1C, CAr), 131.3 (1C, CAr), 131.1 (1C, CAr), 130.9
(1C, CAr), 130.0 (1C, CAr), 129.9 (1C, CAr), 129.8 (1C, CAr), 129.3 (1C,
CAr), 129.2 (1C, CAr), 128.8 (1C, CAr), 128.5 (1C, CAr), 128.4 (1C, CAr),
128.2 (1C, CAr), 127.0 (1C, CAr), 126.8 (1C, CAr), 125.3 (1C, CAr), 125.0
(1C, CAr), 124.4 (1C, CAr), 123.1 (1C, CAr), 122.9 (1C, CAr), 122.7 (1C,
CAr), 122.6 (1C, CAr), 121.4 (1C, CAr), 94.8 (1C, Calkyne), 94.7 (1C, Calkyne),
94.1 (1C, Calkyne), 94.0 (1C, Calkyne), 90.7 (1C, Calkyne), 89.2 (1C, Calkyne),
88.2 (1C, Calkyne), 86.5 (1C, Calkyne), 82.2 (1C, Calkyne), 82.2 (1C, Calkyne),
81.6 (1C, Calkyne), 81.5 (1C, Calkyne), 80.1 (1C, Calkyne), 78.8 ppm (1C,
Calkyne). The peaks of 128.0, 127.7, 127.6 and 127.5 are only visible
in the DEPT-135 experiment, as the signals are overlain by C6D6.
HR-MS (ESI, MeOH) calcd for C50H22Na+: [M+Na]+, 647.1770; found
[M+Na]+, 647.1764.
Bicycle 1: CuCl, Cu(OAc)2, and pyridine were purified according to
a protocol by Scott et al.[21,31,32] Cu(OAc)2·H2O (10 g) was dried by
refluxing in Ac2O (50 mL) overnight, the salt was filtered under N2
and washed with anhydrous THF and dried under vacuum. CuCl
(15 g) was washed with HCl aq. (1m, until the green color disap-
peared), H2O, EtOH, and THF an activated by heating under re-
duced pressure (1708C, 14 h, 0.1 mbar). Pyridine (600 mL) was re-
fluxed over CaH2 for 18 h before distillation. A 1 L round bottom
flask with baffles was filled with pyridine (95 mL) and purged with
Chem. Eur. J. 2021, 27, 6295 –6307
6305 ꢀ 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH