556
H. Germain et al. / Tetrahedron Letters 51 (2010) 554–556
Table 2
Acknowledgements
Results of SNAr with various nucleophiles on 14, 15 and 16
F
The authors would like to acknowledge Dr. Gilles Ouvry, Dr.
F
N
O
N
O
Bernard Barlaam, Dr. Bénédicte Délouvrie, Mr. Fabrice Renaud
and Mr. Christian Delvare for their interest and analytical support
for this sub-series.
N
O
14
15
16
F
Supplementary data
Entry
Benzoxazole
Nucleophile
Yield of substituted
product (%)
Supplementary data (full experimental procedures and sup-
porting LC–MS and 1H and 13C NMR characterisation data) associ-
ated with this article can be found, in the online version, at
81a
OH
17
14
OH
O
18
19
20
14
14
14
72a
O
References and notes
OH
1. For recent methods for C-4-oxy substituted benzoxazoles via cyclisation see:
(a) Brehu, L.; Fernandes, A.-C.; Lavergne, O. Tetrahedron Lett. 2005, 46, 1437–
1440; (b) Ueda, S.; Nagasawa, H. Angew. Chem., Int. Ed. 2008, 47, 6411–6413; (c)
Barlaam, B. C.; Bower, J. F.; Delouvrie, B.; Fairley, G.; Harris, C. S.; Lambert, C.;
Ouvry, G.; Winter, J. J. G. PCT Int. Appl. WO 2009053737, 2009 (includes also C-
7-oxy substituted benzoxazoles).
2. For recent methods for C-7-oxy substituted benzoxazoles via cyclisation see:
(a) Marsden, S. P.; McGonagle, A. E.; McKeever-Abbas, B. Org. Lett. 2008, 10,
2589–2591; (b) Corfield, J. A.; Grimes, R. M.; Harrison, D.; Hartley, C. D.; Howes,
P.D.; Le, J.; Meeson, M. L.; Mordaunt, J.E.; Shah, P.; Slater, M. J.; White, G. V. PCT
Int. Appl. WO 2007071434, 2007.
3. For C-4-hydroxysubstituted benzoxazoles, the most direct method depended
on the reduction of 2-nitroresorcinol: Ausin, C.; Ortega, J.-A.; Robles, J.;
Grandas, A.; Pedroso, E. Org. Lett. 2002, 4, 4073–4075; for the preparation of 7-
oxy substituted benzoxazoles, the most direct method depended on the
nitration and subsequent reduction of Guaiacol (2-methoxyphenol), Kanoo, F.;
Yamane, T.; Kondo, H.; Hashizume, T.; Yamashita, K.; Hosoe, K.; Kuze, F.;
Watanabe, K. Eur. Pat. Appl. EP 333176, 1989.
4. Malamas, M. S.; Manas, E. S.; McDevitt, R. E.; Gunawan, I.; Xu, Z. B.; Collini, M.
D.; Miller, C. P.; Dinh, T.; Henderson, R. A.; Keith, J. C., Jr.; Harris, H. A. J. Med.
Chem. 2004, 47, 5021–5040.
60a
49a
N
OH
O
O
N
O
21
22
14
14
10a
50b
OH
SH
O
O
23
24
25
14
14
14
11b
SH
SH
O
N
49b
5. (a) Hein, D. W.; Alheim, R. J.; Leavitt, J. J. J. Am. Chem. Soc. 1957, 79, 427–429; for
a nice library procedure using polymer bound esters see: (b) Lim, H.-J.; Myung,
D.; Lee, I. Y. C.; Jung, M. H. J. Comb. Chem. 2008, 10, 501–503.
6. Wang, Y.; Sarris, K.; Sauer, D. R.; Djuric, S. W. Tetrahedron Lett. 2006, 47, 4823–
4826.
7. Kangani, C. O.; Kelley, D. E.; Day, B. W. Tetrahedron Lett. 2006, 47, 6497–
6499.
8. Rose, U. J. Heterocycl. Chem. 1992, 29, 551–557.
NH
Tracesc
0a
43b
OH
OH
26
27
15
16
OH
O
9. Wang, F.; Hauske, J. R. Tetrahedron Lett. 1997, 38, 6529–6532.
10. Chang, J.; Kang, Z.; Shifeng, P. Tetrahedron Lett. 2002, 43, 951–954.
11. Bougrin, K.; Loupy, A.; Souflaoui, M. Tetrahedron 1998, 54, 8055–8064.
28
16
32b
O
12. For
a recent large-scale hydroxydeboronation protocol see: Germain,
H.; Harris, C. S.; Renaud, F.; Warin, N. Synth. Commun. 2009, 39, 523–
530.
3–4 equiv of alcohol or thiol, 3–4 equiv of NaH were used in a1,2-dimethoxyethane,
70 °C, 16 h; bNMP used as the solvent, 85 °C, 5–16 h; cpiperidine used as the solvent
at 180 °C.
13. (a) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119–2183. and references
cited therein; (b) Ouellet, S. G.; Bernardi, A.; Angelaud, R.; O’Shea, P.
Tetrahedron Lett. 2009, 50, 3776–3779; (c) Belfield, A. J.; Brown, G. R.;
Foubister, A. J. Tetrahedron 1999, 55, 11399–11428; (d) Brown, G. R.;
Foubister, A. J.; Ratcliffe, P. D. Tetrahedron Lett. 1999, 40, 1219–1222; (e)
Belfield, A. J.; Brown, G. R.; Foubister, A. J.; Ratcliffe, P. D. Tetrahedron 1999, 55,
13285–13300. and corrigendum 2000, 56, 4107.
In conclusion, we have developed surprisingly efficient and
mild conditions for the introduction of nucelophiles, notably oxy-
gen-based, at C-4 and to some extent at C-7 of the benzoxazole ring
in poor to excellent yields.
14. Brunner, H.; Olschewski, G.; Nuber, B. Synthesis 1999, 3, 429–434.