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Regio- and Stereospecific Synthesis of Novel 3-Enynyl-Substituted Thioflavones/Flavones Using a Copper-Free Palladium-Catalyzed Reaction

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journal contribution
posted on 02.09.2005, 00:00 by Manojit Pal, Rambabu Dakarapu, Karuppasamy Parasuraman, Venkataraman Subramanian, Koteswar Rao Yeleswarapu
A variety of 3-enynyl substituted flavones/thioflavones were synthesized via a sequential one-pot procedure using copper-free palladium-catalyzed cross coupling in a simple synthetic operation. The cross coupling between 3-iodo(thio)flavone and a broad range of terminal alkynes was carried out in the presence of Pd(PPh3)2Cl2 and triethylamine to afford the corresponding 3-enynyl derivatives in a regio- and stereoselective fashion. The best results are obtained by employing 3 equiv of the terminal alkynes. The process worked well irrespective of the substituents present on the (thio)flavone ring as well as in the terminal alkynes except arylalkynes. The reaction is quite regioselective, placing the substituent of the terminal alkyne at the far end of the double bond attached with the (thio)flavone ring. The orientation of the (thio)flavonyl and acetylenic moieties across the double bond was found to be syn in the products isolated. A tandem C−C bond-forming reaction in the presence of palladium catalyst rationalized the formation of coupled product. The catalytic process apparently involves heteroarylpalladium formation, regioselective addition to the C−C triple bond of the terminal alkyne, and subsequent displacement of palladium by another mole of alkyne. The present methodology is useful for the introduction of an enynyl moiety at the C-3 position of flavones and thioflavone rings to afford novel compounds of potential biological interest. In the presence of CuI the process afforded 3-alkynyl (thio)flavones in good yields.