V. André et al. / Tetrahedron Letters 49 (2008) 5059–5062
5061
Table 1 (continued)
Entry
Phosphonate
Halo reagenta
Phostone (Y, %)
d(P)
dðCsp2 —XÞ
dðCsp2 —OÞ
O
OMe
O
OMe
O
O
OMe
OH
P
P
P O
6c
h
BIH
30.5
30.6
83.2
89.2
144.2
144.2
Me
( )4
+
Me
Me
I
I
14 (29)
15 (27)
OMe
O
O
O
P O
OMe
OH
n-C4H9
g
BBH
BIH
31.7
113.6
147.5
P
6d
6d
( )4
n-C4H9
n-C4H9
16 (35)
Br
OMe
O
OMe
P O
O
P
O
n-C4H9
OMe
OH
h
30.5
30.3
89.0
92.7
149.6
146.1
P
n-C4H9
+
( )4
I
I
17 (27)
18 (52)
a
BBH: (bis-collidine)bromo hexafluorophosphate. BIH: (bis-collidine)iodo hexafluorophosphate.
2. The reactivity of conjugated acetylenic phosphonates has been reported:
Lahrache, H.; Robin, S.; Rousseau, G. Tetrahedron Lett. 2005, 46, 1635–1637.
3. Peng, A.-Y.; Ding, Y.-X. Tetrahedron 2005, 61, 10303–10308.
4. (a) Rengevich, E. N.; Staninets, V. I.; Shilov, E. A. Dokl. Akad. Nauk SSR 1962, 146,
111–114. For recent reports, see: (b) GowriSankar, S.; Lee, M. J.; Lee, S.; Kim, J.
N. Bull. Korean Chem. Soc. 2004, 25, 1963–1965; (c) Rousseau, G.; Strzalko, T.;
Roux, M.-C. Tetrahedron Lett. 2004, 45, 4503–4505; (d) Woon, E. C. Y.; Dhami,
A.; Mahon, M. F.; Threadgill, M. D. Tetrahedron 2006, 62, 4829–4837; (e) Gao,
M.; Wang, D.-X.; Zheng, Q.-Y.; Huang, Z.-T.; Wang, M.-X. J. Org. Chem. 2007, 72,
6060–6066.
5. (a) Chakravarty, P. K.; Krafft, G. A.; Katzenellenbogen, J. A. J. Biol. Chem. 1982,
257, 610–612; (b) Zupan, L. A.; Weiss, R. H.; Hazen, S. L.; Parnas, B. L.; Aston, K.
W.; Lennon, P. J.; Getman, D. P.; Gross, R. W. J. Med. Chem. 1993, 36, 95–100; (c)
Zheng, J.; Mitchell, A. E.; Jones, A. D.; Hammock, B. D. J. Biol. Chem. 1996, 271,
20421–20425; (d) Mukerjee, N.; Dryjanski, M.; Dai, W.; Katzenellenbogen, J. A.;
Pietruszko, R. J. Protein Chem. 1996, 15, 639–648; (e) Zheng, J.; Wurz, G. T.;
Cadman, T. B.; Degregorio, M. W.; Jones, A. D.; Hammock, B. D. Biochem. Biophy.
Res. Commun. 1997, 241, 13–17; (f) Mitchell, A. E.; Zheng, J.; Hammock, B. D.; Lo
Bello, M.; Jones, A. D. Biochemistry 1998, 37, 6752–6759; (g) Piomelli, D.;
Beltramo, M. Patent WO 9824396, Chem. Abstract. 1998, 129, 62987.; (h) Wu, Z.;
Minhas, G. S.; Wen, D.; Jiang, H.; Chen, K.; Zimniak, P.; Zheng, J. J. Med. Chem.
2004, 47, 3282–3294; (i) Zheng, J.; Liu, G.; Tozkoparan, B.; Wen, D. Med. Chem.
2005, 1, 191–198.
OMe
O
O
OMe
O
O
O
a
P
P
n-C6H13
n-C6H13
I
19 (18%)
8
OMe
O
OMe
O
O
P
P
a
n-C4H9
n-C4H9
I
20 (20%)
18
Scheme 3. Reagents: (a) PPh3, Et3N, HCO2H, Pd(OAc)2.
determine the nature endo or exo of these compounds. We have
reported in Table 1 the chemical shift of these characteristic
carbons and that of the phosphorus atom.
6. Oliver, J. E.; Doss, R. P.; Williamson, R. T.; Carney, J. R.; DeVilbiss, D. E.
Tetrahedron 2000, 56, 7633–7641.
We decided to test also the dehalogenation of these compounds
in view of their potential synthetic applications. Different methods
are reported in the literature in the case of vinyl halides.10 Under
the rather harsh conditions necessary to remove vinyl halides
these phostones appeared somewhat unstable. Messy products
were usually obtained. However, formic acid in the presence of tri-
phenylphosphine and palladium acetate as catalyst11 gave encour-
aging results in the case of iodo derivatives.12 We report in Scheme
3 examples of our results. Work is in progress to improve these
results.
In conclusion, we reported for the first time the formation of
halo enol phostones by electrophilic cyclizations of acetylenic
phosphonate monoesters. These cyclizations allow the formation
of 6–8-membered compounds, either by endo or exo cyclizations.
Compared to the results observed in the case of acetylenic carbox-
ylic acids,4 our results show that with phosphonates, endo cycliza-
tions are usually favoured over exo cyclizations.13 This is
particularly true for the cyclization of phosphonate 6a, since no
5-exo cyclization was observed, whilst pent-4-ynoic acid deriva-
tives led to lactones by exo cyclizations.4,14 The fact that (bis-colli-
dine)halo reagents were used allowed the formation of 8-
membered compounds. These compounds could probably not
obtained using halo reagents such as halogens, NXS or ICl.9
7. General procedure for the halo cyclizations: To
a dichloromethane solution
(5 mL) of (bis-collidine)halo hexafluorophosphate (0.36 mmol, 1.3 equiv) was
added in the dark, in 2 h, a dichloromethane solution (3 mL) of monoester
phosphonate (0.3 mmol). After 1 h at room temperature, the solvent was
removed under vacuum and the residue was purified by liquid
chromatography over silica gel (EtOAc).
8. Compound 7: 1H NMR d 3.75 (d, J 11.0, 3H), 2.85–2.72 (m, 2H), 2.41–2.27 (m,
2H), 2.08–1.94 (m, 2H), 1.49 (quintuplet, J 7.2, 2H), 1.33–1.18 (m, 6H), 0.84 (t, J
6.5, 3H). 13C NMR d 149.9 (d, J 7.5, Csp2–O), 100.7 (d, J 15.7, C–Br), 51.9 (d, J 7.0,
OMe), 33.9 (d, J 4.5, CH2), 31.3 (d, J 6.8, CH2), 28.3 (CH2), 25.9 (CH2), 21.6 (d, J
138.8, CH2), 13.9 (CH3). IR
m
(cmꢀ1) 2979.5 (C–H), 1467.2 (P–O–C), 1382.3,
1097.9, 907.3. HRMS calcd for C11H20O3BrNaP [M+Na+] 333.0231, found
333.0229. Compound 8: 1H NMR d 3.82 (t, J 11.1, 3H), 3.06–2.80 (m, 2H),
2.53–2.44 (m, 2H), 2.19–1.90 (m, 2H), 1.55 (quintuplet, J 8.0, 2H), 1.38–1.23 (m,
6H), 0.9 (t, J 7.5, 3H). 13C NMR d 155.7 (d, J 8.9, Csp2–O), 98.9 (d, J 21.0, C–I), 52.2
(d, J 7.0, OMe), 37.8 (d, J 4.4, CH2), 35.6 (d, J 9.0, CH2), 31.5 (CH2), 28.4 (CH2),
26.4 (CH2), 22.5 (CH2), 21.2 (d, J 127.7, CH2), 14.0 (CH3). IR
H), 1470.2 (P–O–C), 1382.2, 1096.6, 907.3. HRMS calcd for
m
(cmꢀ1) 2985.0 (C–
11H20O3INaP
C
[M+Na+] 381.0092, found 381.0097. Compound 9: 1H NMR d 3.76 (d, J 11.0, 3H),
2.78–2.67 (m, 1H), 2.56–2.37 (m, 3H), 2.13–1.88 (m, 4H), 1.61–1.41 (m, 2H),
1.41–1.22 (m, 2H), 0.88 (t, J 7.0, 3H). 13C NMR d 147.6 (d, J 8.4, Csp2–O), 64.8 (d, J
5.0, C–Br), 52.0 (d, J 7.0, OMe), 37.5 (CH2), 33.8 (CH2), 29.5 (CH2), 25.9 (d, J
134.0, CH2), 22.0 (CH2), 20.8 (d, J 7.0, CH2), 13.7 (CH3). Compound 10: 1H NMR d
3.85 (d, J 11.0, 3H), 2.78–2.67 (m, 1H), 2.56–2.37 (m, 3H), 2.13–1.88 (m, 4H),
1.61–1.41 (m, 2H), 1.41–1.22 (m, 2H), 0.90 (t, J 7.0, 3H). 13C NMR d 149.8 (d, J
8.3, Csp2–O), 110.6 (d, J 5.7, C–Br), 52.3 (d, J 7.0, OMe), 47.0 (CH2), 33.8 (CH2),
27.6 (CH2), 21.7 (CH2), 21.1 (d, J 8.9, CH2), 17.5 (d, J 130.0, CH2), 13.8 (CH3).
Compound 11: 1H NMR d 373 (d, J 10.8, 3H), 2.98–2.87 (m, 1H), 2.64–2.49 (m,
1H), 2.49–2.42 (m, 1H), 2.42–2.28 (m, 1H), 2.07–1.70 (m, 4H), 1.52–1.37 (m,
2H), 1.37–1.23 (m, 2H), 0.87 (t, J 7.2, 3H). 13C NMR d 147.1 (d, J 9.0, Csp2–O), 91.5
(d, J 5.2, C–I), 35.7 (CH2), 32.0 (d, J 6.4, CH2), 32.0 (d, J 6.4, CH2), 31.3 (CH2), 21.8
References and notes
(d, J 128.6, CH2), 21.5 (CH2), 20.0 (d, J 8.4 CH2), 13.8 (CH3). IR
m
(cmꢀ1) 2958.8,
1650.7, 1468.4, 1216.8, 1166.4, 907.3. HRMS calcd for C10H18O3INaP [M+Na+]
1. André, V.; Lahrache, H.; Robin, S.; Rousseau, G. Tetrahedron 2007, 63, 10059–
366.9936, found 366.9937. Compound 12: 1H NMR d 3.80 (d, J 11.2, 3H), 2.89 (t,
10066.