a Reaction conditions: Arylhydrazine hydrochloride (1.0 mmol), Catalyst (2 mol %), base (2 equiv.), co-catalyst (5 mol%), solvent (10 mL), 4 bar CO/O2 with ratio (3:1), byield determined by GC-MS.
Initially, phenylhydrazine hydrochloride 1a with 4 bar CO/O2 with the ratio (3:1) was examined in 1,4 dioxane at 100 °C for 12 h in the presence of 5 mol% Pd/C and K2CO3 as a base, the targeted yield of benzophenone was obtained below 5%. Surprisingly, when CuBr was used as a co-catalyst, the yield of benzophenone was increased to 25% (Table 1, entry 2). Subsequently, we evaluate the various copper co-catalyst, among them CuI was the best and afforded a 56% yield of 2aalong with 12% of iodobenzene byproduct (Table 1, entry 3). Henceforth, CuI co-catalyst was used as a cocatalyst for further study of symmetric biaryl ketone synthesis. Notably, we found that the co-catalyst with molecular oxygen as an oxidant is important for this transformation. Next, we screened the various Palladium sources, and the homogeneous PdCl2(PPh3)2 catalyst was found to be effective compared to the other catalysts (Table 1, entry 9). Then we studied the effects of solvents involves of 1,4 dioxane, THF, DMSO, acetonitrile, and toluene, among these solvents’ acetonitrile is the more effective solvent and provides a good yield of2a, and byproduct 3a was suppressed in this solvent (Table 2, entry 17). The impact of the base was then investigated using a variety of organic and inorganic bases, including Na2CO3, K2CO3, Cs2CO3, Et3N, and DBU. Among these, Na2CO3 is the most effective for driving the C-N bond cleavage process. According to the time and temperature study, a reaction time of 12 hours and a temperature of 100 °C are necessary to achieve the highest yield of desired products (Table 1, entries 20-23).
With the optimal reaction conditions in hand (Table 1, entry 17), We began to explore the substrate scope of various substituted aryl hydrazine hydrochlorides. As concisely in Table 2, Gratifyingly, a series of aryl hydrazines hydrochlorides successfully underwent denitrogenative self-carbonylation reaction to synthesize symmetrical biaryl ketones.
Table 2. Carbonylative homo-coupling reactions of aryl hydrazinesa