The Investigation On Palladium-Catalyzed Carbonylation Of Aromatic Ring C-H Bonds

(Hetero)aryl alkynones are powerful building blocks in organic synthesis where they have been used in the preparation of a wide range of natural products and bioactive heterocycles. Aryl alkynone derivatives have traditionally been synthesized via the Sonogashira coupling of aryl acid chlorides with alkynes. Unfortunately, however, the aryl acid chlorides required for this approach can be unstable and poorly tolerated under the reaction conditions (e.g., indole-3-acid chloride), leading to limitations in the scope of this transformation. Another facile protocol for the synthesis of alkynone derivatives involves the transition-metal catalyzedSonogashira carbonylation reaction between an aryl halide and an alkyne in the presence of carbon monoxide. The advantage of this particular approach is that the starting materials are relatively simple, with aryl iodides and bromides being used in most cases. In2011, Wu et al. reported the carbonylative Sonogashira coupling of aniline and phenylacetylene to generate the corresponding alkynone via the in-situ generated arenediazonium salt, which effectively accelerated the reaction. Over the past few decades, transition-metal catalyzed carbonylation reactions involving the functionalization of aryl C-H bonds have been explored extensively, resulting in the successful syntheses of a variety of different aryl acids, esters, and amides. To date, however, the direct synthesis of aryl alkynones from unactivated arenes has never been reported.Here, we designed and implemented to indole compounds and terminal alkynes as raw materials, through carbonylation method for synthesis of indole-3-alkynone. Examined and determined the reaction condition, the optimal condition was found.Under the condition, high yields and high selectively was achieved. Indole-3-alkynone could react with sodium azide and benzyl bromide to get the corresponding1,2,3-triazole analogues. The main work and results were as follows:Successfully synthesized indole-3-alkynone compounds through carbonylation method. Investigated several different catalyst systems, among them with Pd(OAc)2and CuI catalytic system had a best efficacy. The effect of different temperature on the reaction was investigated and found that at low temperature (90℃) worked best. Experiment results under the conditions of different base show that when K2CO3as base, obviously promoted the reaction. On the investigation to the solvent, found that solvent had a great influence on the reaction. When DMF was as solvent, reaction effect was the best. To reduce the amount of base adverses the reaction, and Pd catalyst and iodine ware essential for the reactions.After screening optimization of reaction conditions, the optimal condition was found to be5mol%Pd(OAc)2,3mol%CuI,1.2mmol I2,1.5mmol K2CO3,3.0mL DMF,0.2MPa CO,90℃24h. Under the optimum reaction conditions, a series of indole compounds and alkyne compounds were smoothly reacted to give the desired products up to83%isolated yield.Indole-3-alkynone reacted with sodium azide and benzyl bromide to successfully synthesis1,2,3-triazole analogues. Reaction condition was as follow:in solvent DMSO, indole-3-alkynone reacted with sodium azide and benzyl bromide at room temperature under stirring, product could be obtained, and the yield was up to91%.