Recent Advances in the Synthesis of Coumarin and Its Derivatives by Using Aryl Propiolates

Abstract

Coumarins (2H‐1‐benzopyran‐2‐one) are a class of natural products extracted from plant with a broad range of biological activities like antitubercular, anti‐inflammatory, anticancer, anticonvulsant, neuroprotective, antiviral, antifungal, antibacterial, antihyperglycemic, anticoagulant, antihypertensive, antiadipogenic, and antioxidant, effects. Therefore, the synthesis of coumarin and its derivatives has become amongst the most attractive compounds over the last two decades in the growth of improved synthetic methods to form various coumarins derivatives. Amongst the reported methods for the construction of coumarins, the pendant arylpropiolate scaffolds served as a highly appealing precursor for coumarins in a single step. This review article describes recent updates on the construction of coumarins using arylpropiolate as substrates.

Mechanistic insight for tunable regioselective cyclization of aryl propiolates with radicals:ipso-versus ortho-cyclization

“…Next, it is suggested that an ester migration takes place at the spiro-radical 5 via carboxyl radical 9 to yield intermediate 8 . 34 For the homolytic cleavage of the C–O bond of the spiro-radical 5a , 5a → 9a , the reaction and activation free energies are 15.3 and 16.0 kcal mol −1 , respectively. For the formation of intermediate 8a from carboxyl radical 9a , 9a → 8a , the reaction and activation free energies are −15.0 and 2.9 kcal mol −1 , respectively.…”

“…However, the general trend is that the reaction proceeds via the oxidation of a radical intermediate to a cation after ortho-or ipso-cyclization as shown in Scheme 1. 34 In addition to coumarin derivatives, styrene derivatives can also be formed depending on the reaction temperature. [35][36][37][38][39] All plausible mechanisms for the reaction of aryl propiolates 1 with various radicals are given in Scheme 1.…”

“…A computational study of both HAS and EAS is carried out. The trifluoromethyl, [40][41][42] 2-furyl 43,44 and acyl 15,17,27,29,34,45,46 radicals were taken into account in the computations. Density functional theory (DFT) and high-level coupled-cluster methods are employed for the computations.…”

Pd(II)/LA‐Catalyzed Intramolecular Hydroarylation of Alkynoates to Construct Coumarins

“…[6][7][8][9] Remarkably, Tunge employed the Fujiwara method to synthesize brominated coumarins which were further derivatized through Suzuki-coupling by utilizing in situ reduced Pd(0) as the catalyst, and Sames employed the PtCl 4 or Au(PPh 3 )Cl/AgSbF 6 catalyzed coumarins synthesis to develop the neuroimaging agents. [10,11] Even that versatile methodologies are continuously explored for the synthesis of those coumarin derivatives, [2][3][4][5] the intramolecular hydroarylation of alkyne still represents the most atomeconomic route; however, up to date, seldom new development was reported for this methodology in recent years. The proposed mechanism for the construction of coumarins through intramolecular hydroarylation of aryl alkynoates was either a CÀ H activation based CMD mechanism or electrophilic aromatic substitution mechanism, [6,12,13] and both require the strong electrophilic capability of the catalyst, such as Pt(IV), Au(III) or Pd(II) with trifluoroacetic acid to enhance its electrophilicity.…”

Recent Methods for Synthesis of Coumarin Derivatives and Their New Applications

“…As a current result, the coumarin heterocyclic ring system is widely used mostly in pharmaceutical industry to build a various functional groups present in the drug molecules. Significant research has been shown to isolate and purify naturally present biological active coumarins from a range of plants, animals, and microbes, and to artificially design and synthesize functionalized coumarin molecules from academic and industry as well with unique heterocyclic structures and characteristics [31][32][33][34][35][36]. Given the importance of coumarin parent compounds and their derivatives in medicinal chemistry, we have gathered diverse methods for the preparation of coumarin and its scaffolds from alkyne type aryl propiolate as suitable starting materials via transition metal and, non-metal mediated catalysis and photo-chemical and radical based transformations.…”