M. Ceborska et al. / Tetrahedron 66 (2010) 9532e9537
9537
126.26þ126.90þ128.95 (ArCeH), 138.55 (Aripso), 157.44 (br s, C]O).
LRMS (ESI): m/z 1465.6 [MþH]þ.
(AreC), 52.94 (OCH3), 69.87þ70.64 (CH2OCH2), 127.60þ128.28
(ArCeH) 137.21 (Aripso) 157.13þ157.31 (C]O). HRMS (ESI) m/z cal-
culated 1121.5270 for C54H78N6O18Na obtained 1121.5355.
4.2.6. Macrocycle cb[1þ1]-1C. Yield: 7% (non-templated reaction).
Pale yellow oil. Rf: 0.64 (95:5 CHCl3/MeOH). tR (HPLC)¼3.85min. 1H
4.2.14. Macrocycle cb[2þ2]-2C. Yield: 29% (non-templated re-
action). Pale yellow oil. Rf: 0.63 (95:5 CHCl3/MeOH). 1H NMR (CDCl3):
NMR (CDCl3):
d 1.77 (br s, CH2CH2CH2, 4H), 3.22e3.63 (m,
OeCH2þNeCH2, 16H), 3.75 (s, OCH3, 6H), 4.49 (s, AreCH2, 4H),
d
1.77 (br s, CH2CH2CH2, 8H), 3.26e3.62 (m, OeCH2þNeCH2, 32H),
3.72 (s, OCH3,12H), 4.44 (s, AreCH2, 8H), 7.16e7.19 (m, AreH, 8H). 13
NMR(CDCl3):
7.08e7.27 (m, AreH, 4H). 13C NMR (CDCl3):
d
28.12þ28.77
C
(CH2CH2CH2), 43.82þ44.82 (NCH2CH2O), 51.19þ51.46 (AreC), 52.85
(OCH3), 68.35þ70.53þ71.04 (CH2OCH2), 126.59þ127.48þ129.30
(ArCeH), 138.60 (Aripso). HRMS (ESI) m/z calculated 439.2444 for
C22H35N2O7 obtained 439.2455.
d
28.13þ28.57 (CH2CH2CH2), 43.74þ44.72 (NCH2CH2O),
50.52þ50.70 (AreC), 52.84 (OCH3), 68.62þ70.34þ70.77 (CH2OCH2),
127.65þ128.31 (ArCeH), 137.32 (Aripso), 157.54þ157.59 (C]O). HRMS
(ESI) m/z calculated 899.4630 for C44H68N4O14Na obtained 899.4616.
4.2.7. Macrocycle cb[2þ2]-1C. Yield: 25% (non-templated reaction).
Pale yellow oil. Rf: 0.45 (95:5 CHCl3/MeOH). tR (HPLC)¼7.32min. 1H
4.2.15. Macrocycle cb[3þ3]-2C. Yield: 9% (non-templated re-
action). Pale yellow oil. Rf: 0.44 (95:5 CHCl3/MeOH). 1H NMR
NMR (CDCl3):
d
1.77 (br s, CH2CH2CH2, 8H), 3.27e3.62 (m,
(CDCl3):
OeCH2þNeCH2, 48H), 3.71 (s, OCH3, 18H), 4.44 (s, AreCH2, 12H),
7.16e7.19 (m, AreH, 12H). 13C NMR (CDCl3):
d
1.78 (br s, CH2CH2CH2, 12H), 3.27e3.64 (m,
OeCH2þNeCH2, 32H), 3.72 (s, OCH3, 12H), 4.54 (s, AreCH2, 8H),
7.07e7.29 (m, AreH, 8H). 13C NMR (CDCl3):
d
28.16þ28.57
d
28.13þ28.51
(CH2CH2CH2), 43.85þ44.76 (NCH2CH2O), 50.72 (AreC), 52.85(OCH3),
68.67þ70.34þ70.74 (CH2OCH2), 126.21þ126.90þ128.97 (ArCeH),
138.58 (Aripso), 157.50 (br s, C]O). HRMS (ESI) m/z calculated
877.4810 for C44H69N4O14 obtained 877.4852.
(CH2CH2CH2), 43.71þ44.55 (NCH2CH2O), 50.36 (br s, AreC), 52.86
(OCH3), 68.71þ70.34þ70.75 (CH2OCH2), 127.60þ128.23 (ArCeH),
137.27 (Aripso), 157.08þ157.50 (C]O). LRMS (ESI): m/z 1315.6
[MþH]þ.
4.2.8. Macrocycle cb[3þ3]-1C. Yield: 10% (non-templated reaction).
Paleyellowoil. Rf:0.29(95:5CHCl3/MeOH). tR (HPLC)¼15.53min. 1HNMR
Supplementary data
(CDCl3):
d
1.78 (br s, CH2CH2CH2,12H), 3.27e3.63 (m, OeCH2þNeCH2,
Supplementary data associated with this article can be found in
48H), 3.72 (s, OCH3, 18H), 4.45 (s, AreCH2, 12H), 7.10e7.30 (m, AreH,
12H). 13C NMR (CDCl3):
d
28.25þ28.54 (CH2CH2CH2), 43.86þ44.72
þ44.74 (NCH2CH2O), 50.67 (AreC), 52.89 (OCH3), 68.78þ70.36þ70.76
(CH2OCH2), 126.20þ126.83þ128.97 (ArCeH), 138.59 (Aripso), 157.04þ
157.51 (C]O). LRMS (ESI): m/z 1315.6 [MþH]þ.
References and notes
1. Brady, P. A.; Bonar-Law, R. P.; Rowan, S. J.; Suckling, C. J.; Sanders, J. K. M. Chem.
Commun. 1996, 319e320.
2. Huc, I.; Lehn, J.-M. Proc. Natl. Acad. Sci. U.S.A. 1997, 94, 2106e2110.
3. Rowan, S. J.; Cantrill, S. J.; Cousins, G. R. L.; Sanders, J. K. M.; Stoddart, J. F. Angew.
Chem., Int. Ed. 2002, 41, 898e952.
4. Corbett, P. T.; Leclaire, J.; Vial, L.; West, K. R.; Wietor, J.-L.; Sanders, J. K. M.; Otto,
S. Chem. Rev. 2006, 106, 3652e3711.
5. Otto, S.; Furlan, R. L. E.; Sanders, J. K. M. Science 2002, 297, 590e593.
6. Otto, S.; Kubik, S. J. Am. Chem. Soc. 2003, 125, 7804e7805.
7. Ludlow, R. F.; Otto, S. J. Am. Chem. Soc. 2008, 130, 12218e12219.
8. Vigato, P. A.; Tamburini, S. Coord. Chem. Rev. 2004, 248, 1717e2128 and citations
therein.
4.2.9. Macrocycle cb[2þ2]-2A. Yield: 45% (non-templated re-
action). Colorless solid. Mp 131e135 ꢁC. Rf: 0.64 (95:5 CHCl3/
MeOH). 1H NMR (CDCl3):
d
3.25e3.45 (m, NCH2CH2O, 16H), 3.71 (s,
OCH3, 12H), 4.43 (s, AreCH2, 8H), 7.08 (br s, AreH, 8H). 13C NMR
(CDCl3):
d
46.93þ47.86 (NCH2CH2O), 51.86 (AreC), 52.95 (OCH3),
70.16 (NCH2CH2O), 127.26þ128.06 (ArCeH) 137.24 (Aripso), 157.28
(C]O). HRMS (ESI) m/z calculated 667.2955 for C32H44N4O10Na
obtained 667.2966.
9. Vigato, P. A.; Tamburini, S.; Bertolt, L. Coord. Chem. Rev. 2007, 251, 1311e1492
and citations therein.
ꢀ
ꢀ
ꢀ
ꢀ
4.2.10. Macrocycle am[2þ2]-2B. 1H NMR (CDCl3):
d 1.98 (br s, NH,
10. Gonzalez-Alvarez, A.; Alfonso, I.; Lopez-Ortiz, F.; Aguirre, A.; Garcõa-Granda, S.;
Gotor, V. Eur. J. Org. Chem. 2004, 1117e1127.
4H), 3.00e3.50 (m, OeCH2þNeCH2, 24H), 3.60 (s, AreCH2,
11. Gonzalez-Alvarez, A.; Alfonso, I.; Gotor, V. Chem. Commun. 2006, 2224e2226.
12. Wessjohann, L. A.; Rivera, D. G.; Leon, F. Org. Lett. 2007, 23, 4733e4736.
13. Alfonso, I.; Bolte, M.; Bru, M.; Burguete, M. I.; Luis, S. V.; Rubio, J. J. Am. Chem.
Soc. 2008, 130, 6137e6144.
8H),7.00e7.10 (m, AreH, 8H). LRMS (ESI): m/z 501.4 [MþH]þ.
4.2.11. Macrocycle am[3þ3]-2B. 1H NMR (CDCl3):
d 1.99 (br s, NH,
14. Ulrich, S.; Lehn, J.-M. Angew. Chem., Int. Ed. 2008, 47, 2240e2243.
€
4H), 3.00e3.50 (m, OeCH2þNeCH2, 24H), 3.62 (s, 8H, CH2N),
15. Saggiomo, V.; Luning, U. Eur. J. Org. Chem. 2008, 4329e4333.
7.01e7.11 (m, AreH, 8H). LRMS (ESI): m/z 751.6 [MþH]þ.
€
16. Saggiomo, V.; Luning, U. Chem. Commun. 2009, 3711e3713.
17. Liu, X.; Warmuth, R. J. Am. Chem. Soc. 2010, 128, 14120e14127.
18. Borisova, N. E.; Reshetova, M. D.; Ustynyuk, Y. A. Chem. Rev. 2007, 107, 46e79
and citations therein.
19. Aguiari, A.; Brianese, N.; Tamburini, S.; Vigato, P. A. Inorg. Chim. Acta 1995, 235,
233e244 and citations therein.
20. Ugras, H. I.; Basaran, I.; Kilic, T.; Cakir, U. J. Heterocycl. Chem. 2006, 43,
1679e1683.
21. Kraessig, G. Makromol. Chem. 1955, 17, 131e153.
22. Carvalho, S.; Delgado, R.; Drew, M. G. B.; Felix, V. Dalton. Trans. 2007,
2431e2439.
4.2.12. Macrocycle cb[2þ2]-2B. Yield: 36% (non-templated re-
action). Colorless solid. Mp 118e122 ꢁC. Rf: 0.66 (95:5 CHCl3/MeOH).
1H NMR (CDCl3):
d
3.53þ3.29e3.61 (sþm, OCH2CH2OþNCH2CH2O,
24H), 3.73 (s, OCH3, 12H), 4.55 (s, AreCH2, 8H), 7.08þ7.14 (br sþbr s,
AreH, 8H).13C NMR (CDCl3):
d
45.72þ46.52 (NCH2CH2O), 51.19þ51.28
(AreC), 52.96 (OCH3), 70.09þ70.60 (CH2OCH2), 127.66þ128.35
(ArCeH) 137.18 (Aripso) 157.12þ157.33 (C]O). HRMS (ESI) m/z calcu-
lated 755.3479 for C36H52N4O12Na obtained 755.3470.
23. Poulsen, S.-A.; Gates, P. J.; Cousins, G. R. L.; Sanders, J. K. M. Rapid Commun. Mass
Spectrom. 2000, 14, 44e48.
24. Lienard, B. M. R.; Huting, R.; Lassaux, P.; Galleni, M.; Frere, J.-M.; Schofield, C. J.
J. Med. Chem. 2008, 51, 684e688.
ꢀ
€
ꢁ
4.2.13. Macrocycle cb[3þ3]-2B. Yield: 9% (non-templated re-
action). Pale yellow oil. Rf: 0.56 (95:5 CHCl3/MeOH). 1H NMR
25. Poulsen, S.-A.; Vu, H. In Dynamic Combinatorial Chemistry; Miller, B. L., Ed.; John
Wiley: Hoboken, NJ, 2010; pp 201e228.
26. In particular cases, this can be obtained by NMR (e.g., see Ref. 14), however for
the libraries studied in this project, signals overlapping and the inability to
isolate free imines as references excluded using this methodology.
27. Ziach, K.; Jurczak, J. Org. Lett. 2008, 10, 5159e5162.
(CDCl3):
3.71 (s, OCH3, 18H), 4.53 (s, AreCH2, 8H), 7.13þ7.18 (br sþbr s, AreH,
12H). 13C NMR (CDCl3):
45.91þ46.65 (NCH2CH2O), 51.19þ51.28
d
3.52þ3.46e3.59 (sþm, OCH2CH2OþNCH2CH2O, 36H),
d