Palladium-Catalyzed Synthesis Of C-Allylcoumarins

Coumarins are important structural units that are widespread in many naturally and biologically active compounds, also a kind of important organic chemical raw materials and intermediates, widely used in the pharmaceutical, pesticide, spices and other chemical industry.The key compounds in the overall synthetic route were identified to be 7-hydroxycoumarins and 7-hydroxy-4-methylcoumarins. The functionalized 7-hydroxy-8-iodocoumarins were prepared by treating 7-hydroxycoumarin with 12/KI/20% NH3·H2O and then isolating it in 48%-52.8% yield after purification, The optimum conditions is n (hydroxycoumarin):n (iodine):n (KI)=1.0:1.2:0.5,25 ? under reaction 1h.Eleven 7-alkoxy -8-iodocoumarin derivatives from these two hydroxycoumarins were synthesized via Williamson reaction. The optimized conditions of Williamson reaction were: n(7-Hydroxy -8-iodocoumarins):n(alkylhalides):n(anhydrous potassium carbonate): n(TBAB)=1:1.5:2.5:0.1, reaction in acetone at 70?80 ? for 6-10 h, the yields were in the range of 69%-86%.Nineteen 8-ally or 8-prenylcoumarin derivatives from these 7-alkoxy-8-iodocoumarins were synthesized via Stille cross-coupling reaction. The optimum conditions for the cross-coupling are as follows:7-alkoxy-8-iodocoumarin (1 mmol) and allyltributyltin (1.5 mmol) catalyzed by Pd (PPh3)4 (5 mol%) with LiCl (4 mmol) in DMF (15 mL) at 80 ? for 4-6h, the yields were in the range of 35%-70%.