Communications
Scheme 4. Preparation of tricyclic heterocycles starting from N-acylpyr-
roles.
water (10 mL) was added. The mixture was extracted with diethyl
ether (3 30 mL), and the combined extracts were washed with brine,
dried over Na2SO4, and concentrated in vacuo. Purification by flash
chromatography (hexane/diethyl ether 10:1) provided 4b (200 mg,
83% yield) as a white solid, m.p. 77.9–78.98C.
À
Scheme 2. Chemoselective C H activation. Reaction conditions:
a) Pd(OAc)2 (5 mol%), p-Tol3P (10 mol%), Cs2CO3 (1.2 equiv), 1108C,
12 h;b) Pd(OAc) 2 (5 mol%), p-Tol3P (10 mol%), Cs2CO3 (2.2 equiv),
1108C, 24 h.
Received: January 11, 2006
Published online: April 25, 2006
À
Keywords: C H activation · domino reactions ·
nitrogen heterocycles · palladium
.
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2000, 33, 511.
Scheme 3. Tentative reaction sequence for the ring closure.
À
[3] “Activation of C Hbonds: catalytic reactions”: a) F. Kakiuchi,
S. Murai, Top. Organomet. Chem. 1999, 3, 47; b) G. Dyker,
Angew. Chem. 1999, 111, 1808; Angew. Chem. Int. Ed. 1999, 38,
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À
cyclization with a C Hactivation, leading to the heterocycles
16a–c in 74–85% yield and demonstrating the broad scope of
this type of ring closure (Scheme 4).
In summary, we have reported new Pd-catalyzed cycliza-
tions leading to condensed N-heterocycles. The key step of
these ring closures is a chemoselective intramolecular C H
activation of a methyl group at position 2 of a pyrrole ring.
Further studies on the reaction mechanism and scope are
currently underway in our laboratories.
À
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Experimental Section
Synthesis of 4b starting 2c (entry 2 of Table 2): A mixture of the aryl
bromide 2c (322 mg, 1.0 mmol), Pd(OAc)2 (11 mg, 5 mol%), tri(p-
tolyl)phosphine (30 mg, 10 mol%), and Cs2CO3 (391 mg, 1.2 mmol)
was heated at 1108C in toluene (5 mL) under N2 in a sealed tube for
12 h. After the reaction mixture had cooled to room temperature,
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 3462 –3465