9526
A. Sliwa et al. / Tetrahedron 66 (2010) 9519e9527
J¼3.9, 6.9 Hz, 1H), 3.85 (m, 1H), 3.66 (dd, J¼3.9, 7.4 Hz, 1H), 2.72 (m,
2H), 2.24 (t, J¼7.5 Hz, 2H), 2.02e2.10 (m, 4H), 1.59e1.72 (m, 4H),
d
¼174.2, 173.8, 172.4, 171.7, 165.5, 164.9, 130.9, 130.8, 130.6, 130.0,
55.6, 55.2, 45.4, 45.1, 36.8, 36.5, 36.3, 36.1, 31.9, 31.8, 31.7, 28.4, 28.3,
1.36e1.50 ppm (m, 4H); 13C (75 MHz, CDCl3):
d
¼173.6, 171.3, 164.7,
28.2, 28.1, 24.7, 24.4, 23.3, 22.8 ppm; IR:
n
¼3323, 2926, 2854, 1796,
138.4, 138.3, 115.0, 114.8, 55.8, 45.0, 36.5, 35.8, 33.5 (2C), 28.4 (2C),
1697, 1678, 1533 cmꢁ1; HRMS: calcd for C30H44N4O6Na 579.31531,
found 579.31433.
24.8, 23.5 ppm; IR:
n
¼3290, 2852e3080, 1797, 1780, 1693, 1651,
1537 cmꢁ1
329.1846.
; HRMS: calcd for C17H26N2O3Na 329.1841, found
4.3.6. Compound (17b). Yield: 43% (78 mg from 0.69 mmol of 13b).
20
Rf¼0.46 (EtOAc); [
a]
ꢁ10.7 (c 1.1, CHCl3); 13C (125 MHz, CDCl3):
D
4.2.5. (S)-N-(1-Hept-6-enoyl-2-oxoazetidin-3-yl)-N-(methyl)hept-6-
enamide (13c). Compound 13c was synthesized according to the
procedure described above for the synthesis of compound 12c from
d
¼174.1, 171.4, 164.5, 131.4, 130.9, 130.6, 130.4, 63.0, 61.9, 43.1, 36.0,
35.4, 35.2, 35.1, 32.5, 31.9, 31.6, 31.4, 24.1, 24.0, 23.4, 22.8 ppm; IR:
n
¼2851e2976, 1790, 1695, 1651 cmꢁ1
;
HRMS: calcd for
b-lactam 11c (336 mg, 1.08 mmol) and 6-heptenoyl chloride. Flash
C28H40N4O6Na 551.28401, found 551.28341.
column chromatography (hexane/EtOAc 3/2) provided 13c as
20
a colorless oil (263 mg, 76%). Rf¼0.28 (hexane/EtOAc 3/2); [
a
]
4.3.7. Compound (17c). Yield: 40% (20 mg from 0.17 mmol of 13c).
D
20
þ13.3 (c 3.5, CHCl3); 1H NMR (300 MHz, CDCl3):
d
¼5.77 (m, 2H),
Rf¼0.47 (EtOAc); [
a
]
ꢁ9.1 (c 3.0, CHCl3); 13C (125 MHz, CDCl3):
D
4.89e5.02 (m, 5H), 3.81 (m, 1H), 3.63 (dd, J¼3.9, 7.4 Hz, 1H), 3.05 (s,
d
¼174.0, 173.9, 171.6, 164.5, 164.4, 130.6, 130.5, 130.4, 130.2, 63.1,
3H), 2.73 (m, 2H), 2.34 (m, 2H), 2.06 (m, 4H), 1.66 (m, 4H), 1.43 ppm
62.5, 43.2, 43.1, 36.6, 36.5, 33.6, 33.5, 33.4, 32.3, 32.1, 32.0, 29.2,
(m, 4H); 13C (75 MHz, CDCl3):
d
¼173.8, 171.3, 164.4, 138.5, 138.4,
29.0, 28.9, 28.8, 23.9, 23.8, 23.6, 23.5 ppm; IR:
n
¼2851e3003, 1786,
114.9, 114.8, 62.9, 43.1, 36.5, 35.4, 33.6, 33.5, 33.4, 28.6, 28.4, 24.1,
1736, 1716 cmꢁ1; HRMS: calcd for C32H48N4O6Na 607.34661, found
607.34582.
23.5 ppm; IR:
n
¼2858e3074, 1790, 1738, 1703, 1651 cmꢁ1; MS
(APCI): m/z: 320.95 (M); HRMS: calcd for C18H29N2O3 321.21782,
found 321.21822.
Acknowledgements
4.3. General procedure for RCM
This work was supported by the Interuniversity Attraction Pole
(IAP P6/19 PROFUSA), F.R.S.-FNRS, UCL and ULg (computational
facilities). G.D. and J.M.-B. are senior research associates of the
F.R.S.-FNRS (Belgium). J.-L.H.J. thanks the Belgian National Fund for
Scientific Research (FNRS) (FRFC 2.4555.08), the Special Fund for
Research (FSR) and the faculty of medicine of UCL for financial
support on this research (LTQ-Orbitrap). Dr. Astrid Zervosen is ac-
Grubbs catalyst (second generation) (0.05 equiv) was added to
a stirred solution of b-lactam (1 equiv) in dry CH2Cl2 (5 mM) and
the solution was stirred at reflux under argon for 4 h. Then a second
addition of Grubbs catalyst (0.05 equiv) was made and then re-
action was additionally stirred at reflux for 20 h. Then the solvent
was removed under reduced pressure and the crude product was
purified thrice by column chromatography (hexane/EtOAc), to
provide products as pale-brown oil.
ꢀ
knowledged for the R39 testing. Ir. Raoul Rozenberg, Dr. Cecile Le
ꢀ
Duff and Dr. Marie-France Herent have contributed to the structural
analysis.
4.3.1. (S)-tert-Butyl 2,13,16-trioxo-1,14-diazabicyclo[13.1.1]heptadec-
Supplementary data
7-ene-14-carboxylate (14c). Yield: 9% (43 mg from 1.22 mmol of
20
9c). Rf¼0.51 (hexane/EtOAc 7/3); [
a
]
ꢁ32.4 (c 2.8, CHCl3); 13C
D
The Supplementary data for this paper includes experimental
details for compounds 6e8, 18e21, structural data for compounds
6e8, 9a, be13a, b, 18c, 19b, ce21b, c, NMR spectra of all new
compounds, ESI and APCI mass spectra for compounds 14c, 15b,
ce17b, c, generation of conformers, graphics of relative energies of
precursors/cyclic monomers, heat of formation for precursors
9aec, 12aec and 13aec, and testing protocol versus R39. Supple-
mentary data related to this article can be found online at
(125 MHz, CDCl3):
d
¼176.6, 172.6, 164.2, 151.3, 131.1, 130.6, 85.4,
59.7, 44.6, 38.3, 38.2, 32.1, 31.5, 30.5, 28.9, 28.1, 24.8, 22.7 ppm; IR:
n
¼2854e2976, 1799, 1738, 1697 cmꢁ1
;
HRMS: calcd for
C20H30N2O5Na 401.20469, found 401.20442.
4.3.2. Compound (15b). Yield: 44% (229 mg from 1.47 mmol of 9b).
Rf¼0.53 (hexane/EtOAc 3/2); [
a
]
20 ꢁ9.1 (c 3.0, CHCl3); 13C (75 MHz,
D
CDCl3):
d
¼175.7, 175.4, 171.4, 164.1, 163.9, 151.4, 151.3, 85.5, 85.1,
57.8, 57.5, 43.8, 43.7, 37.7, 37.4, 34.8, 31.9, 31.8, 31.7, 31.5, 28.0, 24.5,
22.6 ppm; IR:
for C36H52N4O10Na 723.35756, found 723.35643.
n
¼2853e2970, 1797, 1744, 1701 cmꢁ1; HRMS: calcd
References and notes
ꢀ
4.3.3. Compound (15c). Yield: 10% (46 mg from 1.22 mmol of 9c).
1. (a) Gradillas, A.; Perez-Castells, J. Angew. Chem., Int. Ed. 2006, 45, 6086e6101;
20
Rf¼0.45 (hexane/EtOAc 7/3);
[
a
]
þ5.8 (c 4.4, CHCl3); 13C
(b) Conrad, J. C.; Fogg, D. E. Curr. Org. Chem. 2006, 10, 185e202; (c) Majumdar,
K. C.; Rahaman, H.; Roy, B. Curr. Org. Chem. 2007, 11, 1339e1365; (d) Clavier, H.;
Grela, K.; Kirshning, A.; Mauduit, M.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46,
6786e6801; (e) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int. Ed.
2005, 44, 4490e4527; (f) Brik, A. Adv. Synth. Catal. 2008, 350, 1661e1675.
2. (a) Monfette, S.; Fogg, D. E. Chem. Rev. 2009, 109, 3783e3816; (b) Monfette, S.;
Crane, A. K.; Duarte Silva, J. A.; Facey, G. A.; dos Santos, E. N.; Araujo, M. H.;
Fogg, D. E. Inorg. Chim. Acta 2010, 363, 481e486.
D
(125 MHz, CDCl3):
d
¼175.6, 175.5, 171.5, 171.4, 164.5, 164.4, 151.4,
151.3, 130.7, 130.6, 130.5, 130.3, 85.5, 57.4, 57.2, 43.9, 43.8, 38.4, 38.2,
36.5, 32.3, 32.2, 32.1, 28.8, 28.7, 28.0, 24.1, 24.0, 23.7, 23.4 ppm; IR:
n
¼2856e2928, 1799, 1742, 1697 cmꢁ1
;
HRMS: calcd for
C40H60N4O10Na 779.42017, found 779.41947.
3. (a) Creighton, C. J.; Leo, G. C.; Du, Y.; Reitz, A. B. Bioorg. Med. Chem. 2004, 12,
4375e4385; (b) Chen, G.; Kirschning, A. Chem.dEur. J. 2002, 8, 2717e2729.
4. (a) Tzur, E.; Ben-Asuly, A.; Diesendruck, C. E.; Goldberg, I.; Lemcoff, N. G. Angew.
Chem., Int. Ed. 2008, 47, 6422e6425; (b) Diesendruck, C. E.; Ben-Asuly, A.;
Goldberg, I.; Lemcoff, N. G. Chim. Oggi 2010, 28, 15e18.
5. Pandian, S.; Hillier, I. H.; Vincent, M. A.; Burton, N. A.; Ashworth, I. W.; Nelson,
D. J.; Percy, J. M.; Rinaudo, G. Chem. Phys. Lett. 2009, 476, 37e40.
6. (a) Urbach, A.; Dive, G.; Marchand-Brynaert, J. Eur. J. Org. Chem. 2009, 11,
1757e1770; (b) Urbach, A.; Dive, G.; Tinant, B.; Duval, V.; Marchand-Brynaert, J.
Eur. J. Med. Chem. 2009, 44, 2071e2080.
4.3.4. Compound (16b). Yield: 35% (30 mg from 0.34 mmol of 12b).
20
Rf¼0.32 (EtOAc); [
a
]
ꢁ15.6 (c 2.2, CHCl3); 13C (75 MHz, CDCl3):
D
d
¼174.4, 171.0, 165.8, 131.5, 130.8, 55.7, 46.0, 35.4, 34.5, 31.8, 31.6,
24.3, 22.0 ppm; IR:
n¼3284e3387, 2906e2930, 1784, 1693, 1676,
1655, 1527 cmꢁ1; HRMS: calcd for C26H36N4O6Na 523.25271, found
523.25171.
7. Miller, M. J.; Mattingly, P. G.; Morrison, M. A.; Kerwin, J. F., Jr. J. Am. Chem. Soc.
1980, 102, 7026e7032.
8. Qabar, M. N.; Kahn, M. Tetrahedron Lett. 1996, 37, 965e968.
4.3.5. Compound (16c). Yield: 28% (46 mg from 0.42 mmol of 12c).
20
Rf¼0.48 (EtOAc); [
a
]
þ13.3 (c 2.4, CHCl3); 13C (125 MHz, CDCl3):
D