Study On The Synthesis Of Substituted Dihydropyrazoles, Indolizines And 3-Styrylcoumarins Compounds Starting From Unsaturated Hydrocarbon

Unsaturated hydrocarbon (including alkenes, alkynes, aromatics) are important staple product of petroleum and petrochemical industries. And it is also significant precursors in organic synthesis. In scientific point of view, the functionalization of unsaturated hydrocarbon is of great importance due to promoting the advancement of human material civilization and its core position in scientific development. Up to now, there are nine Nobel Prizes in chemistry about the unsaturated hydrocarbons. In 2010, the palladium catalyzed Heck-type reaction, recognized with Nobel Prized, has become a powerful tool to prepare substituted olefins. In this context, we reported the synthesis of dihydropyrazoles, indolizines and 3-styrylcoumarins compounds starting from unsaturated hydrocarbon.(1) Pyrazolines play an important role in organic synthesis and medicinal chemistry. Pyrazoline derivatives are reported to possess antitumor, immunosuppressive, antibacterial, antitubercular agents, anti-inflammatory, antidiabetic, antidepressant, antimalarial, antiamoebic. In particular, some trisubstituted dihydropyrazole derivatives serve as valuable precursors in various biologically and pharmaceutically active organic molecules. Due to the attractive medicinal properties of the dihydropyrazole skeleton, various efficient approaches have been developed for the preparation of these compounds. Nevertheless, the synthesis of substituted dihydropyrazoles directly from simple and readily available substrates is still in great demand. We now report novel methodology for the synthesis of dihydropyrazoles from hydrazines and propargyl alcohols using t-BuOK (KTB) as a catalyst.(2) In the last decades, impressive achievements have been made in enhancing the efficiency of direct C-H bonds activation of heteroaromatics using various transition metal catalysts such as Pd, Ru, Rh, Cu, Ir, and others. It has been realized that transition metal catalysts stand out in the area of C-C coupling that proceeds via a C-H activation pathway. However, relatively little work has focused on the unreactive C(sp3)-H bonds, because the C(sp3)-H bonds are less acidic and lack proximal empty low-energy or filled high-energy orbitals that readily interact with orbitals of the metal. This is generally more difficult to form a chelation-assisted carbon-metal bond. In this regard, the efficient and atom-economic activation of C(sp3)-H bonds have emerged as an attractive and challenging goal. To the best of our knowlege, there have been no reports in the literature concerning the rare earth metal catalyzed activation of C(sp3)-H bonds. As a result of development on the transition-metal-catalyzed C-H functionalization in our group, herein, we firstly describe a new samarium-catalyzed C(sp3)-H bonds activation of 2-alkylazaarenes with propargylic alcohols for the formation of indolizines, under mild conditions with minimal waste production.(3) Decarboxylative coupling reactions have become a powerful tool for regioselective C-C and C-heteroatom bonds formation, thus providing new protocols for Heck-type reactions, oxidative arylations, redox-neutral cross-coupling reactions, and allylations. Among those, alkenyl acids act as cross-coupling components by a metal-promoted decarboxylation process and are used in construction of C-C, C-N, C-S, and C-P bonds because of their stable, low cost, diversity, ready availability, and the nontoxic byproduct (CO2). From environmental and economic perspectives, the development of organic synthesis using inexpensive and stable material would be of significant importance. Herein, we disclose an efficient, economic route for rapid synthesis of 3-styrylcoumarins via palladium-catalyzed decarboxylative coupling of cinnamic acids employing coumarins.