4900
Y. Lee, M. J. Kelly / Tetrahedron Letters 47 (2006) 4897–4901
4. (a) Beak, P.; Snieckus, V. Acc. Chem. Res. 1982, 15, 306;
(b) Chauder, B.; Green, L.; Snieckus, V. Pure Appl. Chem.
1999, 71, 1521.
N
O
5. (a) Maleczka, R. E., Jr.; Shi, F.; Holmes, D.; Smith, M.
R., III. J. Am. Chem. Soc. 2003, 125, 7792–7793; (b)
Hoarau, C.; Pettus, T. R. R. Synlett 2003, 127–137; (c)
Guo, Z.; Schultz, A. G.; Antoulinakis, E. G. Org. Lett.
2001, 3, 1177–1180; (d) Marchueta, I.; Olivella, S.; Sola,
L.; Moyano, A.; Pericas, M. A.; Riera, A. Org. Lett. 2001,
3, 3197–3200; (e) Serra, S.; Fuganti, C.; Moro, A. J. Org.
Chem. 2001, 66, 7883–7888; (f) Hashmi, A. S. K.; Frost, T.
M.; Bats, J. W. J. Am. Chem. Soc. 2000, 122, 11553–11554;
(g) Gevorgyan, V.; Yamamoto, Y. J. Organomet. Chem.
1999, 576, 232–247.
H
N
O
c, d
a, b
O
OH
12
N
N
O
O
N
H
28
O
OH
27
6. Webb, K. S.; Levy, D. Tetrahedron Lett. 1995, 36, 5117–
5118.
Scheme 7. Solid-phase synthesis using 12. Reagent and conditions: (a)
m-Tolylboronic acid, KF, Pd(II), THF, 65 ꢁC, 16 h. (b) LiOH,
dioxane/H2O (4:1), 110 ꢁC, 3 h. (c) 3-Aminopyridine, HBTU, DIEA,
DCM, rt, 16 h. (d) 50% TFA/DCM, 3 min.
7. Ishiyama, T.; Murata, M.; Miyaura, N. J. Org. Chem.
1995, 60, 7508–7510.
8. Chloro(di-2-norbornylphosphino)(20-dimethylamino-1,10-
biphenyl-2-yl)palladium(II). See also: Liu, B.; Moffett, K.
K.; Joseph, R. W.; Dorsey, B. D. Tetrahedron Lett. 2005,
46, 1779–1782.
In summary, we have demonstrated the synthesis of
phenols or pyridine-2-ones by oxidation of arylboro-
nates which were prepared from arylbromides.17 Since
a variety of arylbromides is readily available, this unified
arylboronation/oxidation protocol provides an access to
substituted phenols or pyridine-2-ones which may not
be easily prepared by other methods. We also have
developed a number of solid-phase methodologies suit-
able for rapid parallel synthesis of substituted phenols
and pyridine-2-one. The bromides of the resin-bound
templates (9–12) have been efficiently replaced with var-
ious building blocks, such as boronic acids, amides,
amines, and acetylenes by well known palladium- or
copper-catalyzed coupling. When combined with other
on-resin functional group manipulations demonstrated
in this report, a very unique set of small molecule
libraries can be generated. Focused libraries prepared
using solid-phase methods described here will be
reported in due course.
9. Klapars, A.; Huang, X.; Buchwald, S. L. J. Am. Chem.
Soc. 2002, 124, 7421–7428.
10. Other solid-phase synthesis approaches using 11. Reagent
and conditions: (a) LiOH, dioxane/H2O (4:1), 16 h. (b)
N,O-Dimethylhydroxylamine
hydrochloride,
HOBt,
EDCI, DIEA, DCM/DMF, 16 h. (c) CH3MgBr, THF,
2 h. (d) N,N0-Dimethylformamide diethylacetal, 120 ꢁC,
3 h. (e) Guanidine hydrochloride, MeONa, EtOH, 90 ꢁC,
16 h. (f) 50% TFA/DCM, 3 min. (g) NaI, CuI, N,N0-
dimethylethylenediamine, Na2CO3, dioxane, 110 ꢁC, 5 h.
(h) 3-Ethynylpyridine, Cu(phen)(PPh3)Br, K2CO3, tolu-
ene, 110 ꢁC, 16 h. (i) m-Tolylboronic acid, KF, Pd (II),
THF, 65 ꢁC, 16 h.
Br
OH
Br
O
d, e, f
h
a, b, c
11
N
O
g
,
,
f
H2N
N
i, f
Acknowledgments
N
OH
OH
The authors wish to thank Mr. Brandon Campbell and
Dr. Robert Schiksnis for their analytical support.
O
O
Supplementary data
11. Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124,
14844–14845.
12. Gujadhur, R. K.; Bates, C. G.; Venkataraman, D. Org.
Lett. 2001, 3, 4315–4317.
13. Paul, R.; Hallett, W. A.; Hanifin, J. W.; Reich, M. F.;
Johnson, B. D.; Lenhard, R. H.; Dusza, J. P.; Kerwar, S.
S.; Lin, Y.; Pickett, W. C.; Seifert, C. M.; Torley, L. W.;
Tarrant, M. E.; Wrenn, S. J. Med. Chem. 1993, 36, 2716–
2725.
Supplementary data associated with this article can
References and notes
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