F. C. Pigge et al. / Tetrahedron 61 (2005) 5363–5371
5369
4.24 (t, 4H, JZ4.8 Hz), 6.98–7.06 (m, 4H), 7.51 (ddd, 2H,
JZ1.6, 7.0, 8.7 Hz), 7.98 (dd, 2H, JZ1.6, 7.8 Hz). 13C
NMR (75 MHz, CDCl3) d 68.9, 69.6, 71.3, 77.4, 80.1, 82.8,
113.5, 120.8, 126.5, 132.7, 135.5, 159.4, 176.1. IR (thin
film) n (cmK1) 2092, 1650. HRMS (FABC, NBA) calcd for
C24H23O6 [MCH]C 407.1494; found 407.1502.
4.8 Hz), 7.17–7.21 (m, 1H), 7.39–7.47 (m, 3H), 7.82 (dd,
4H, JZ2.4, 4.8 Hz), 7.92 (t, 1H, JZ1.5 Hz), 8.58 (d, 2H,
JZ1.5 Hz). 13C NMR (75 MHz, CDCl3) d 55.8, 68.2, 69.5,
70.8, 71.1, 117.4, 120.1, 123.3, 129.7, 129.9, 132.5, 134.2,
135.8, 137.7, 138.1, 140.1, 160.1, 163.0, 193.8, 195.2. IR
(thin film) n (cmK1) 1664. HRMS (FABC, NBA) calcd for
C36H34O9Na [MCNa]C 633.2100; found 633.2104. Anal
Calcd for C36H34O9 (CHCl3)0.5: C 65.40, H 5.19. Found: C
65.00, H 5.19.
4.2.6. ortho-Tetra(ethylene glycol)-linked bis(ethynyl
ketone) [precursor to 18]. 83%, oil. H NMR (300 MHz,
1
CDCl3) d 3.56–3.59 (m, 4H), 3.61 (s, 2H), 3.64–3.67 (m,
4H), 3.82 (t, 4H, JZ4.8 Hz), 4.14 (t, 4H, JZ4.8 Hz), 6.89–
6.94 (m, 4H), 7.42 (ddd, 2H, JZ1.6, 7.3, 8.4 Hz), 7.86 (dd,
2H, JZ1.6, 8.1 Hz). 13C NMR (75 MHz, CDCl3) d 68.8,
69.4, 70.8, 71.2, 80.5, 82.8, 113.5, 120.7, 126.5, 132.4,
135.5, 159.4, 176.2. IR (thin film) n (cmK1) 2091, 1650.
HRMS (FABC, NBA) calcd for C26H27O7 [MCH]C
451.1757; found 451.1757. Anal Calcd for
C26H26O7$(H2O)0.2: C 68.77, H 5.82. Found: C 68.85, H
5.79.
4.3.2. Crownophane 13. 49%, mp 183–184 8C (hexanes/
EtOAc). 1H NMR (300 MHz, CDCl3) d 3.67–3.75 (m, 8H),
3.90 (t, 4H, JZ4.2 Hz), 4.23 (t, 4H, JZ4.2 Hz), 7.01 (d, 4H,
JZ8.8 Hz), 7.54–7.57 (m, 2H), 7.63–7.67 (m, 1H), 7.81 (d,
4H, JZ8.8 Hz), 7.87–7.92 (m, 3H), 8.57 (d, 2H, JZ1.5 Hz).
13C NMR (75 MHz, CDCl3) d 68.2, 69.4, 70.8, 71.0, 114.4,
128.9, 129.7, 130.4, 132.5, 133.4, 134.2, 135.8, 136.8,
137.7, 140.0, 162.0, 193.8, 195.4. IR (thin film) n (cmK1
)
1652. HRMS (FABC, NBA) calcd for C35H33O8 [MCH]C
581.2175; found 581.2174. Anal Calcd for C35H32O8: C
72.40, H 5.56. Found: C 72.28, H 5.43.
4.2.7. ortho-Penta(ethylene glycol)-linked bis(ethynyl
ketone) [precursor to 19]. 86%, oil. H NMR (300 MHz,
1
4.3.3. Crownophane 14. 29%, mp 174–175 8C (CHCl3/
hexanes). 1H NMR (300 MHz, CDCl3) d 3.66–3.73 (m,
12H), 3.87 (t, 4H, JZ4.4 Hz), 4.20 (t, 4H, JZ4.4 Hz), 6.97
(d, 4H, JZ8.8 Hz), 7.49–7.54 (m, 2H), 7.60–7.63 (m, 1H),
7.80 (d, 4H, JZ8.8 Hz), 7.84–7.87 (m, 2H), 7.94 (t, 1H, JZ
1.5 Hz) 8.52 (d, 2H, JZ1.5 Hz). 13C NMR (75 MHz,
CDCl3) d 68.1, 69.7, 71.0, 71.1, 71.3, 114.6, 128.9, 129.5,
130.4, 132.6, 133.4, 134.1, 134.6, 136.8, 137.9, 140.1,
163.1, 193.7, 195.3. IR (thin film) n (cmK1) 1650. HRMS
(FABC, NBA) calcd for C37H37O9 [MCH]C 625.2438;
found 625.2432. Anal Calcd for C37H36O9 (CHCl3)0.84: C
62.69, H 5.12. Found: C 62.74, H 5.16.
CDCl3) d 3.59 (s, 2H), 3.65–3.69 (m, 8H), 3.74–3.77 (m,
4H), 3.93 (t, 4H, JZ4.8 Hz), 4.25 (t, 4H, JZ4.8 Hz), 6.98–
7.04 (m, 4H), 7.51 (ddd, 4H, JZ1.6, 7.1, 8.7 Hz), 7.96 (dd,
2H, JZ1.6, 7.8 Hz). 13C NMR (75 MHz, CDCl3) d 68.9,
69.6, 70.8, 70.9, 71.2, 77.4, 80.6, 113.5, 120.8, 132.4, 135.5,
159.5. IR (thin film) n (cmK1) 2091, 1650. HRMS (FABC,
NBA) calcd for C28H31O8 [MCH]C 495.2019; found
495.2015. Anal Calcd for C28H30O8$(H2O)0.2: C 67.51, H
6.12. Found: C 67.47, H 6.16.
4.3. General procedure for macrocyclization-
preparation of crownophane 11
4.3.4. Crownophane 15. 33%, mp 50–55 8C (hexanes/
EtOAc). H NMR (300 MHz, CDCl3) d 3.69 (s, 4H), 3.84
The reaction leading to 11 is representative. From separate
addition funnels, bis(alkyne) 9 (1.00 g, 2.45 mmol) in
50 mL of toluene and enaminone 1013 (0.51 g, 2.45 mmol)
in 50 mL of toluene were simultaneously added dropwise to
150 mL of refluxing toluene. Once the addition was
complete, the reaction was maintained for 5 days, at
which time TLC indicated complete consumption of starting
materials. The toluene was evaporated and the tarry residue
was purified by flash column chromatography (1:1 hexanes/
EtOAc) to afford 11 as a yellow solid (0.45 g, 34%). An
analytical sample was obtained by recrystallization from
hexanes/EtOAc, mp 190–191 8C. 1H NMR (300 MHz,
CDCl3) d 3.75 (s, 3H), 3.86–3.90 (m, 8H), 4.29 (t, 4H,
JZ4.2 Hz), 7.02 (t, 4H, JZ8.7 Hz), 7.19–7.22 (m, 1H),
7.37–7.49 (m, 3H), 7.57–7.75 (m, 4H), 7.84 (s, 1H), 8.77 (s,
2H). 13C NMR (75 MHz, CDCl3) d 55.8, 68.1, 69.5, 71.3,
114.4, 114.6, 120.1, 123.3, 129.9, 130.1, 132.3, 134.0,
136.9, 137.7, 138.2, 140.7, 160.1, 162.8, 194.0, 195.2. IR
1
(dd, 4H, JZ3.6, 5.4 Hz), 3.90 (s, 3H), 4.12 (dd, 4H, JZ3.6,
5.4 Hz), 7.12–7.22 (m, 4H), 7.38–7.51 (m, 8H), 8.07 (t, 1H,
JZ1.5 Hz), 8.51 (d, 2H, JZ1.5 Hz). 13C NMR (75 MHz,
CDCl3) d 55.8, 68.1, 69.7, 71.0, 114.4, 116.8, 119.6, 120.1,
121.9, 123.2, 129.9, 130.4, 133.7, 133.9, 138.0, 138.1,
138.2, 139.6, 158.7, 160.1, 194.9, 195.2. Anal Calcd for
C34H30O8$(H2O)0.5: C 70.94, H 5.25. Found: C 70.54, H
5.64.
4.3.5. Crownophane 16. 32%, 165–166 8C (hexanes/
EtOAc). 1H NMR (300 MHz, CDCl3) d 3.62–3.69 (m,
8H), 3.84 (dd, 4H, JZ4.0, 5.5 Hz), 3.88 (s, 3H), 4.14 (dd,
4H, JZ4.0, 5.5 Hz), 7.16–7.23 (m, 4H), 7.35–7.50 (m, 8H),
8.17 (t, 1H, JZ1.5 Hz), 8.47 (d, 2H, JZ1.5 Hz). 13C NMR
(75 MHz, CDCl3) d 55.8, 68.1, 69.8, 70.9, 71.0, 114.3,
116.8, 119.9, 120.0, 122.3, 123.1, 129.7, 130.2, 133.3,
134.1, 137.8, 138.0, 139.0, 158.6, 159.9, 194.7, 194.8. IR
(thin film) n (cmK1) 1658. HRMS (FABC, NBA) calcd for
C36H35O9 [MCH]C 611.2281; found 611.2280. Anal Calcd
for C36H34O9: C 70.81, H 5.61. Found: C 70.73, H 5.73.
(thin film)
n
(cmK1
)
1739. Anal Calcd for
C34H30O8$(H2O)0.5: C 70.94, H 5.25. Found: C 70.92, H
5.38. Crownophanes 12–19 were prepared using the
procedure described above from the appropriate bis(alkyne)
precursor and either enaminone 10 or its unsubstituted
analogue.13
4.3.6. Crownophane 17. 33%, 1H NMR (300 MHz, CDCl3)
d 3.38 (s, 4H), 3.56 (t, 4H, JZ4.1 Hz), 4.12 (t, 4H, JZ
4.1 Hz), 6.99 (d, 2H, JZ8.7 Hz), 7.11 (t, 2H, JZ7.5 Hz),
7.48–7.53 (m, 6H), 7.58–7.63 (m, 1H), 7.82–7.85 (m, 2H),
8.39 (d, 2H, JZ1.5 Hz), 8.59 (t, 1H, JZ1.5 Hz). 13C NMR
4.3.1. Crownophane 12. 33%, mp 168–169 8C (CHCl3/
hexanes). 1H NMR (300 MHz, CDCl3) d 3.69–3.76 (m, 8H),
3.89–3.92 (m, 7H), 4.22–4.25 (m, 4H), 7.01 (dd, 4H, JZ2.4,