LETTER
Facile Anchoring of the Bisphosphonate Moiety
1867
(12) For examples of the use of Cu(OTf)2 in organic synthesis,
see: (a) Jones, S.; Smanmoo, C. Org. Lett. 2005, 7, 3271.
(b) Bayer, A.; Endeshaw, M. M.; Gautun, O. R. J. Org.
Chem. 2004, 69, 7198. (c) Endeshaw, M. M.; Bayer, A.;
Hansen, L. K.; Gautun, O. Eur. J. Org. Chem. 2006, 5249.
(d) Hertweck, C. J. Prakt. Chem. 2000, 342, 316.
(13) General Procedure
References and Notes
(1) (a) Widler, L.; Jaeggi, K. A.; Glatt, M.; Müller, K.;
Bachmann, R.; Bisping, M.; Born, A. R.; Corseti, R.;
Guiglia, G.; Jeker, H.; Klein, R.; Ramseier, U.; Schmid, J.;
Schreiber, G.; Seltenmeyer, Y.; Green, J. R. J. Med. Chem.
2002, 45, 3721. (b) Rodan, G. A. Annu. Rev. Pharmacol.
Toxicol. 1998, 38, 375. (c) Prestwood, K. M.; Pilbeam, C.
C.; Raisz, L. G. Annu. Rev. Med. 1995, 46, 249. (d) Mundy,
G. R. Annu. Rev. Med. 2002, 53, 337.
To a solution of diazo bisphosphonate 1a (100 mg, 0.318
mmol) and alcohol (0.350 mmol) in 6 mL of anhyd toluene
was added Cu(OTf)2 (1.2 mg, 0.003 mmol). The mixture was
heated under reflux for 8 or 12 h and then evaporated under
reduced pressure. The residue was purified directly by flash
chromatography on silica column (acetone–CH2Cl2, 1:1) to
afford the desired product.
(2) Russel, R. G. G.; Rogers, M. J. Br. J. Rheumatol. 1997, 36,
10; Suppl. 1.
(3) (a) Pecherstorfer, M.; Herrmann, Z.; Body, J.-J.; Manegold,
C.; Degardin, M.; Clemens, M. R.; Thurlimann, B.; Tubiana-
Hulin, M.; Steinhauer, E. U. J. Clin. Oncol. 1996, 14, 268.
(b) Clezardin, P.; Fournier, P.; Boissier, S.; Peyruchaud, O.
Curr. Med. Chem. 2003, 10, 173. (c) Guenin, E.; Ledoux,
D.; Oudar, O.; Lecouvet, M.; Kraemer, M. Anticancer Res.
2005, 25, 1139. (d) Wilheim, M.; Kunzman, V.; Eckstein,
S.; Reimer, P.; Weissinger, F.; Ruediger, T.; Tony, H. P.
Blood 2003, 102, 200.
(4) Kubicek, V.; Rudocsky, J.; Kotek, J.; Hermann, P.; Vander
Elst, L.; Muller, R. N.; Kollar, Z. I.; Wolterbeek, H. Th. h.;
Peters, J. A.; Lukes, I. J. Am. Chem. Soc. 2005, 127, 16477.
(5) (a) Wang, L.; Yang, Z.; Gao, J.; Xu, K.; Gu, H.; Zhang, B.;
Zhang, X.; Xu, B. J. Am. Chem. Soc. 2006, 128, 13358.
(b) Sawicki, M.; Siaugue, J. M.; Jacopin, C.; Moulin, C.;
Bailly, T.; Burgada, R.; Meunier, S.; Baret, P.; Pierre, J. L.;
Taran, F. Chem. Eur. J. 2005, 11, 3689. (c) Challeix, V.;
Lecouvey, M. Tetrahedron Lett. 2007, 48, 703.
All new compounds have been characterized by 1H NMR,
13C NMR, 31P NMR, IR, and mass spectroscopy.
Selected Data:
Compound 5b: 1H NMR (400 MHz, CDCl3): d = 1.29 (t,
J = 7.2 Hz, 6 H), 1.31 (t, J = 7.2 Hz, 6H), 4.04 (t, J = 17.8
Hz, 1 H), 4.08–4.20 (m, 8 H), 4.80 (s, 2 H), 7.26–7.38 (m, 5
H) ppm. 13C NMR (100 MHz, CDCl3): d = 16.32–16.41 (m),
63.16 (d, J = 3.0 Hz), 63.19 (d, J = 3.0 Hz), 63.31 (d, J = 3.0
Hz), 63.34 (d, J = 3.0 Hz), 71.50 (t, J = 157.0 Hz), 75.58 (t,
J = 5.0 Hz), 128.16, 1128.26, 128.67, 136.34 ppm. 31P NMR
(160 MHz, CDCl3): d = 16.09 (s, 2 P) ppm. MS (ESI/TOF):
m/z = 395 [M + H]+.
Compound 5c: 1H NMR (400 MHz, CDCl3): d = 1.29 (t,
J = 7.2 Hz, 6 H), 1.32 (t, J = 7.2 Hz, 6 H), 4.18–4.30 (m, 8
H), 4.89 (t, J = 17.8 Hz, 1 H), 4.80 (s, 2 H), 7.02 (t, J = 7.6
Hz, 1 H), 7.09 (d, J = 7.6 Hz, 2 H), 7.29 (t, J = 7.6 Hz, 2 H)
ppm. 13C NMR (100 MHz, CDCl3): d = 16.26 (d, J = 2.9
Hz), 16.29 (d, J = 2.9 Hz), 16.36 (d, J = 2.9 Hz), 16.39 (d,
J = 2.9 Hz), 63.50 (d, J = 3.2 Hz), 63.53 (d, J = 3.2 Hz),
63.87 (d, J = 3.2 Hz), 63.90 (d, J = 3.2 Hz), 72.35 (t,
J = 157.0 Hz), 116.23, 122.64, 129.45, 158.71 (t, J = 4.5 Hz)
ppm. 31P NMR (160 MHz, CDCl3): d = 14.51 (s, 2 P) ppm.
MS (ESI/TOF): m/z = 381 [M + H]+.
(d) Burgada, R.; Bailly, T.; Prangé, T.; Lecouvey, M.
Tetrahedron Lett. 2007, 26, 2315.
(6) (a) Sturz, G.; Appéré, G.; Breistol, K.; Fodstad, O.;
Schwartsmann, G.; Hendriks, H. R. Eur. J. Med. Chem.
1992, 27, 825. (b) Herczegh, P.; Buxton, Y. B.; McPherson,
J. C.; Kovacs-Kulyassa, A.; Brewer, P. D.; Sztaricskai, F.;
Stroebel, G. G.; Plowman, K. M.; Farcasiu, D.; Hartmann, J.
F. J. Med. Chem. 2002, 45, 2338. (c) Kultyshev, R. G.; Liu,
J.; Liu, S.; Tjarks, W.; Soloway, A. H.; Shore, S. G. J. Am.
Chem. Soc. 2002, 124, 2614. (d) Gil, C.; Han, Y.; Opas, E.
E.; Rodan, G. A.; Ruel, R. J.; Seedor, J. G.; Tyler, P. C.;
Young, R. N. Bioorg. Med. Chem. 1999, 7, 901.
(7) (a) Mallard, I.; Benech, J. M.; Lecouvey, M.; Leroux, Y.
Phosphorus, Sulfur Silicon Relat. Elem. 2000, 162, 15.
(b) Gouault-Bironneau, S.; Deprèle, S.; Sutor, A.;
Montchamp, J.-P. Org. Lett. 2005, 7, 5909. (c) Lecouvey,
M.; Mallard, I.; Bailly, T.; Burgada, R.; Leroux, Y.
Tetrahedron Lett. 2001, 42, 8475. (d) Guenin, E.; Degache,
E.; Liquier, J.; Lecouvey, M. Eur. J. Org. Chem. 2004,
2983. (e) Stepinski, D. C.; Nelson, D. W.; Zalupski, P. R.;
Herlinger, A. W. Tetrahedron 2001, 57, 8637. (f) Migianu,
E.; Guénin, E.; Lecouvey, M. Synlett 2005, 425.
Compound 5d: 1H NMR (400 MHz, CDCl3): d = 1.30 (t,
J = 6.8 Hz, 12 H), 4.06–4.25 (m, 11 H), 5.19–5.30 (m, 2 H),
5.79–5.88 (m, 1 H) ppm. 13C NMR (100 MHz, CDCl3): d =
16.24–16.31, 63.29 (d, J = 3.0 Hz), 63.32 (d, J = 3.0 Hz),
63.52 (d, J = 3.0 Hz), 63.55 (d, J = 3.0 Hz), 70.87 (t,
J = 157.0 Hz), 74.72 (t, J = 4.7 Hz), 119.19, 133.13 ppm. 31
P
NMR (160 MHz, CDCl3): d = 16.29 (s, 2 P) ppm. MS (ESI/
TOF): m/z = 345 [M + H]+.
Compound 5e: 1H NMR (400 MHz, CDCl3): d = 1.31 (t,
J = 7.2 Hz, 6 H), 1.32 (t, J = 7.2 Hz, 6 H), 4.10 (t, J = 17.2
Hz, 1 H), 4.10–4.24 (m, 8 H), 4.77 (s, 2 H), 6.34 (dd, J = 3.2,
1.2 Hz, 1 H), 6.40 (d, J = 3.2 Hz, 1 H), 7.41 (d, J = 1.2 Hz, 1
H) ppm. 13C NMR (100 MHz, CDCl3): d = 16.30–16.41 (m),
63.17 (d, J = 3.0 Hz), 63.20 (d, J = 3.0 Hz), 63.42 (d, J = 3.0
Hz), 63.46 (d, J = 3.0 Hz), 66.11 (t, J = 5.2 Hz), 70.15 (t,
J = 157.0 Hz), 110.35, 111.47, 143.37, 149.92 ppm. 31
P
(g) Ruzziconi, R.; Ricci, G.; Gioiello, A.; Couthon-Gourvès,
H.; Gourvès, J.-P. J. Org. Chem. 2003, 68, 736.
(h) Migianu, E.; Mallard, I.; Bouchemal, N.; Lecouvey, M.
Tetrahedron Lett. 2004, 45, 4511.
NMR (160 MHz, CDCl3): d = 15.93 (s, 2 P) ppm. HRMS:
m/z calcd for C14H26O8P2Na: 407.1001; found: 407.1014.
Compound 5f: 1H NMR (400 MHz, CDCl3): d = 0.79 (s, 3
H), 1.15 (s, 3 H), 1.23–1.29 (m, 2 H), 1.31 (t, J = 7.2 Hz, 6
H), 1.32 (t, J = 7.2 Hz, 6 H), 1.58 (m, J = 8.0 Hz, 1 H), 1.67–
1.76 (m, 2 H), 1.80–1.82 (m, 1 H), 1.86–1.88 (m, 1 H), 1.96–
1.99 (m, 1 H), 2.28 (qt, J = 7.6 Hz, 1 H), 3.51 (d, J = 7.2 Hz,
(8) Lecerclé, D.; Sawicki, M.; Taran, F. Org. Lett. 2006, 8,
4283.
(9) (a) Haigh, D. Tetrahedron 1994, 50, 3177. (b) Wood, H. B.;
Buser, H.-P.; Ganem, B. J. Org. Chem. 1992, 57, 178.
(10) (a) Wong, F. M.; Wang, J.; Hengge, A. C.; Wu, W. Org. Lett.
2007, 9, 1663. (b) Nowlan, D. T.; Gregg, T. M.; Davies, H.
M. L.; Singleton, D. A. J. Am. Chem. Soc. 2003, 125, 15902.
(11) (a) Cox, G. G.; Kulagowski, J. J.; Moody, C. J.; Sie, E.-B. H.
B. Synlett 1992, 975. (b) Cox, G. G.; Miller, D. J.; Moody,
C. J.; Sie, E.-B. H. B. Tetrahedron 1994, 50, 3195.
2 H), 3.85 (t, J = 17.8 Hz, 1 H), 4.10–4.21 (m, 8 H) ppm. 13
NMR (100 MHz, CDCl3): d = 16.30–16.41 (m), 18.08,
20.04, 23.44, 23.96, 26.52, 35.97, 38.97, 40.74, 42.22,
C
62.97–63.17 (m), 73.47 (t, J = 157.0 Hz), 79.15 (t, J = 4.3
Hz) ppm. 31P NMR (160 MHz, CDCl3): d = 16.21 (s, 2 P)
ppm. MS (ESI/TOF): m/z = 441 [M + H]+.
Synlett 2007, No. 12, 1863–1868 © Thieme Stuttgart · New York