Transition Metal Rhodium-Catalyzed Borylation/Protonation Tandem Reactions Of Arynes

Stilbenes are privileged molecules in medicinal chemistry because of their wide range of different biological activities. Particularly, hydroxylated stilbenes are largely presented in nature and play a significant role in antioxidant and antitumor. Their activity has stimulated studies directed at the development of cardiovascular drugs or cancer therapeutics. Therefore, the synthesis and bioactivity evaluation of hydroxylated stilbene derivatives receive much attention and interests in medicinal chemistry. Literature methods for the synthesis of hydroxylated stilbenes include conventional Wittig reaction and Heck coupling reaction. After the investigation,we found that hydroxylated stilbenes could be synthesized by rhodium-catalyzed borylation/protonation tandem reactions of arynes.After the optimization of catalysts, solvents, bases, temperature, catalyst amount, ligands and hydrogen sources, we found that the reaction of 0.20 mmol 2-hydroxylated diphenyl acetylene derivatives could indeed afford the 2-hydroxylated(E)-toluylene derivatives in good yields upon 2.5 mol % [Rh(cod)Cl]2 catalyst, 1.2 eq.(0.24 mmol)(Bpin)2 as boron reagent, 3.0 eq.(0.60 mmol) KOAc as base and 0.2 mL H2 O as hydrogen source in o.8 mL dioxane at room temperature for 4 h under the protection of nitrogen.In addition, we synthesized different substrates to research the universality of reaction(two of them were new compounds.). A series of stilbenes were obtained in moderate to good yields via rhodium-catalyzed borylation/protonation tandem reactions(one of them was new compounds among them. All of the new compounds and final products were characterized by melting point, 1H NMR, 13 C NMR and HR-MS. The determination of trans structure was further confirmed by X-ray single crystal diffraction analysis of compound(E)-2-(4-methoxystyryl)phenol. At the end of the reaction, we put forward a reasonable mechanism to explain the reactions.The reaction condition was pretty mild, and it could effectively inhibiting the production of cyclization products. Rhodium-catalyzed borylation/protonation tandem reactions of arynes were novel and significant.