Selective Palladium-Catalyzed Direct Arylation of FuroACTHNUTRGNEU[GN 3,2-b]pyridines
General Procedure for Direct Arylation at C-7
Furo
N
PACHTUNGTRENNUNG(t-
Bu)2Me·HBF4 (12 mol%), and Pd
AHCTUNGTRENNUNG
weighed and placed in a screw-cap vial equipped with a mag-
netic stir bar under argon. PivOH (60 mol%) was weighed,
dissolved in mesitylene, and added in the vial. Finally, the
aryl halide (1 equiv.) was added (if liquid, otherwise, it was
introduced at the beginning with the other solids). The reac-
tion mixture was then vigorously stirred at 1508C during the
indicated time period. The mixture was cooled down to
room temperature, diluted with EtOAc, and washed with
water. The aqueous layer was extracted twice with EtOAc.
The combined organic layers were washed with brine, dried
over MgSO4, filtered, and evaporated under reduced pres-
sure. The residue was purified by flash chromatography over
silica gel to afford the desired product.
Scheme 3. Proposed CMD mechanism.
not observed under the optimized conditions. There-
fore, the C-7 arylation process would also indicate
a CMD mechanism
Conclusions
In conclusion, a palladium-catalyzed procedure for
the regioselective two-step diarylation on positions 3
and 7 of furoACHTUNGTRENNUNG[3,2-b]pyridines has been developed. The
Acknowledgements
combination of a furan and a pyridine ring has creat-
ed a new reactivity. Whereas C H activation on posi-
This work was financially supported by the Centre National
de la Recherche Scientifique, the Institut Curie and the
Agence Nationale de la Recherche (Grant ANR-08-PCVI-
0031-CHEMISPIKE).
À
tion 3 was predictable, the C-7 arylation of furo
N
b]pyridine was unexpected since no such reactivity of
substructures or analogues has been ever described
without directing groups. Both C-3 and C-7 proce-
dures tolerate many functional groups and allow one References
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AHCTUNGTRENNUNG
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General Procedure for Direct Arylation at C-3
Furo
A
PACTHNGUTRENNU(G t-
Bu)2Me·HBF4 (12 mol%), and Pd
AHCTUNGTRENNUNG
weighed and placed in a screw-cap vial equipped with a mag-
netic stir bar under argon. PivOH (60 mol%) was weighed,
dissolved in mesitylene, and added in the vial. Finally, the
aryl halide (2 equiv.) was added (if liquid, otherwise, it was
introduced at the beginning with the other solids). The reac-
tion mixture was then vigorously stirred at the indicated
temperature (1058C or 858C) during the indicated time
period. The mixture was cooled down to room temperature,
diluted with EtOAc, and washed with water. The aqueous
layer was extracted twice with EtOAc. The combined organ-
ic layers were washed with brine, dried over MgSO4, fil-
tered, and evaporated under reduced pressure. The residue
was purified by flash chromatography over silica gel to
afford the desired product.
Adv. Synth. Catal. 2012, 354, 2751 – 2756
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2755