A copper-mediated C6-selective dehydrogenative heteroarylation of 2-pyridones with 1,3-azoles has been developed. The reaction proceeded smoothly by twofold C-H cleavage even in the absence of noble-metal catalysts. The observed site selectivity was directed by a pyridyl substituent on the nitrogen atom of the pyridone ring. This directing group was readily removed after the coupling event, thus leading to 2-pyridone derivatives with a free N-H group. Moreover, in some cases, catalytic turnover of the Cu salt was also possible with the ideal terminal oxidant: molecular oxygen in air.

A copper-mediated dehydrogenative biaryl cross-coupling of naphthylamines and 1,3-azoles has been developed. The key to its success is the introduction of N,N-bidentate coordination system based on the picolinamide directing group. The reaction proceeds smoothly without precious transition metal catalysts and provides highly π-extended heterobiaryls directly.

A copper-mediated formally dehydrative biaryl coupling of azine N-oxides and oxazoles has been developed. The C-C bond-forming process proceeds, accompanied by the removal of the oxygen atom from the azine core, to directly afford the azine-oxazole biaryl linkage. Moreover, this system requires no noble transition metals such as palladium and rhodium, which are common promotors in the related dehydrogenative couplings with the azine N-oxide. Thus, the present protocol can provide a unique and less expensive approach to the azine-containing biheteroaryls of substantial interest in pharmaceutical and medicinal chemistry.

A copper-mediated C6-selective dehydrogenative heteroarylation of 2-pyridones with 1,3-azoles has been developed. The reaction proceeded smoothly by twofold CÀ H cleavage even in the absence of noble-metal catalysts. The observed site selectivity was directed by a pyridyl substituent on the nitrogen atom of the pyridone ring. This directing group was readily removed after the coupling event, thus leading to 2pyridone derivatives with a free N À H group. Moreover, in some cases, catalytic turnover of the Cu salt was also possible with the ideal terminal oxidant: molecular oxygen in air.

Instrumentation and Chemicals S1 Experimental Procedures S2 Characterization Data for Products S3-S17 Instrumentation and Chemicals 1 H and 13 C NMR spectra were recorded at 400 MHz and 100 or 150 MHz, respectively, for CDCl3 solutions. MS data were obtained by EI, FAB, or APCI. GC analysis was carried out using a silicon OV-17 column (i. d. 2.6 mm x 1.5 m) or a CBP-1 capillary column (i. d. 0.5 mm x 25 m). TLC analyses were performed on commercial glass plates bearing 0.25-mm layer of Merck Silica gel 60F 254. Silica gel (Wakogel 200 mesh) was used for column chromatography. Unless otherwise noted, materials obtained from commercial suppliers were used without further purification. o-Xylene was stored on slices of sodium. Anhydrous Cu(OAc) 2 was purchased from Wako Pure Chemical Co. All thiophenecarboxamides 1 were synthetized from the corresponding thiophenecarboxylic acids or thiophenecarbonyl chlorides and 8-aminoquinoline. 1 N-(2-pyrimidyl)indoles and N-(2-pyridyl)indole were prepared according to the literature. 2