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The coupling reaction of o-iodobenzoic acid with terminal alkynes by using a catalyst system of 10% Pd/C-Et3N-CuI-PPh3 has been studied in a variety of solvents. 3-Substituted isocoumarins were formed in good yields and with good regioselectivity when the reaction was performed in EtOH.

A general and one-pot synthesis of 2-alkyl/aryl substituted indoles via a tandem Pd/C mediated coupling/5-endo-dig cyclization of terminal alkynes (including acetylenic carbinols) with o-iodoanilides in water is reported. The reaction is carried out using PPh 3 and CuI as co-catalysts and 2-aminoethanol as a base. The reaction appears to tolerate a variety of functional groups present in the alkynes and does not require the use of any organic co-solvent.The indole nucleus is a frequently found unit in many natural products and diverse biologically active molecules. 2 Interesting pharmacological properties, such as antithrombotic, 3 anticancer, 4 histamine H 3 receptor antagonism 5 etc. exhibited by the various 2-substituted indoles have led to a continued interest in the practical synthesis of these compounds. Among the classical methods for the synthesis of indole ring, the Fischer indole synthesis, the Batcho-Leimgruber synthesis (from o-nitrotoluenes and dimethylformamide acetals), the Gassman synthesis (from N-haloanilines), the reductive cyclization of o-nitrobenzylketones and the Madelung cyclization of N-acyl-o-toluidines are often used. However, the introduction of an aryl group at the 2-position of an indole ring is usually achieved by de novo indole ring construction 6 either by Fischer indole synthesis or more popularly by transition metal mediated reactions, 7 especially by palladium catalyzed protocols. 8-10 Palladium-catalyzed annulation of o-haloanilines with terminal alkynes (under Sonogashira reaction conditions) or internal alkynes (under Larock's conditions) has been employed widely due to the versatile nature of these protocols, increased functional group tolerance and improved yields (Scheme 1). Despite being quite versatile, the synthesis of 2-substituted indoles employing terminal alkynes often involves a twostep process i.e. Sonogashira coupling of o-haloanilines with terminal alkynes followed by the cyclization of the resulting 2-alkynylanilines in the presence of various reagents (e.g. metal alkoxides, halides or Lewis acids). 11 Moreover, cyclization of anilides having an alkynol moiety at the 2-position yielded quinolines/2,3-dihydro-4(1H)-quinolones rather than indoles. 11d Very recently, a one-pot synthesis of 2-substituted indoles has been reported in the presence of Pd(II)-NaY zeolite catalysts. 8a However, the reaction was carried out in a sealed tube and appeared to be unsuitable for the preparation of these compounds in a large scale. Scheme 1 Palladium-catalyzed synthesis of indolesPalladium-promoted reactions in aqueous media are a focus of current research 12,13 because water-based synthetic processes are inherently safer as well as inexpensive (especially for industrial-scale processes). Therefore, the use of water-soluble catalysts 13g and water-soluble phosphine ligands 13f has been explored successfully. The use of Pd/ C-CuI-PPh 3 as a catalyst system for efficient Sonogashira coupling has also been reported. 14,15 All these Pdcatalyzed reactions are usually carried out i...

We herein report the efficient syntheses of 4-(hetero)aryl-substituted 1-chlorophthalazines via heteroarylation of arenes/heteroarenes through AlCl(3)-induced C[bond]C formation reactions. A number of (hetero)arenes were reacted with 1,4-dichlorophthalazine to give aryl/heteroaryl-substituted phthalazines in good to excellent yields. Many of them were converted to the corresponding phthalazin-1(2H)-ones.

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