Angewandte
Chemie
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(Table 2, entry 3).Similarly, the treatment of 1a with the
benzoyl diazomethane 2e gave the corresponding 1-arylated
indazole 4c in high yield (Table 2, entry 4).The analogous
reaction with the silylaryl triflate 1b afforded the meta isomer
4d in 68% yield with excellent regioselectivity (Table 2,
entry 5).This result clearly indicates that the nucleophile
reacts at the position meta to a methoxy group rather than at
the ortho position.
In summary, we have developed a facile, efficient, and
general method for the synthesis of N-unsubstituted indazoles
and 1-arylated indazoles by the 1,3-dipolar cycloaddition of
benzynes with diazomethane derivatives.By changing the
reaction conditions, the controlled synthesis of either of the
two products is possible.A variety of indazoles can be
obtained in good to high yields under very mild conditions.
Further studies on the application of the present methodology
to the synthesis of biologically active compounds are in
progress.
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Experimental Section
Synthesis of 3a: Ethyl diazoacetate (2a; 62 mL, 0.6 mmol) was added
to a solution of 1a (125 mL, 0.5 mmol), KF (87 mg, 1.5 mmol), and
[18]crown-6 (462 mg, 1.75 mmol) in THF (2 mL) under an argon
atmosphere in a pressure vial.The reaction mixture was stirred at
room temperature for 24 h, then filtered through a short pad of
Florisil and eluted with ethyl acetate.The filtrate was concentrated,
and the residue was purified by chromatography on silica gel (eluent:
hexane/EtOAc) to afford 3a (76.5 mg, 80%).
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Ed. 2004, 43, 3935 – 3938; i) H.Yoshida, H.Fukushima, J.
Ohshita, A.Kunai J. Am. Chem. Soc. 2006, 128, 11040 – 11041.
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Synthesis of 4a: Ethyl diazoacetate (2a; 26 mL, 0.25 mmol) was
added to a solution of 1a (125 mL, 0.5 mmol) and CsF (228 mg,
1.5 mmol) in CH3CN (2.0 mL) under an argon atmosphere in a
pressure vial.The reaction mixture was stirred at room temperature
for 24 h, then filtered through a short pad of Florisil and eluted with
ethyl acetate.The filtrate was concentrated, and the residue was
purified by chromatography on silica gel (eluent: hexane/EtOAc) to
afford 4a (52.6 mg, 79%).
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Jin, Z.Huo, Y.Yamamoto, J. Am. Chem. Soc. 2003, 125, 7786 –
7787.
Received: January 9, 2007
Published online: March 27, 2007
Keywords: 1,3-dipolar cycloaddition · arynes ·
.
1
[8] a) The H and 13C NMR spectra of product 3a are identical to
diazo compounds · heterocycles · indazoles
those described in the literature: A.Schmidt, L.Merkel, W.
Eisfeld, Eur. J. Org. Chem. 2005, 2124 – 2130; b) the identity of
products 3e, 3 f, 3 f’, 3g, 3g’, and 4d was confirmed unambig-
uously by spectroscopic methods, in particular by NOE, COSY,
and HMBC analysis; see the Supporting Information.
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Angew. Chem. Int. Ed. 2007, 46, 3323 –3325
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3325