Synthesis of 2,3,6,8-tetrasubstituted chromone scaffolds

A useful and efficient synthetic strategy to 2,3,6,8-tetrasubstituted chromone derivatives has been developed. 2-Aryl/styryl-8-bromo-6-chloro-3-hydroxychromone derivatives were synthesized and used as scaffolds by introducing a variety of substituents in the 3-, 6-, and 8-positions using palladium-mediated reactions. Excellent regioselectivity in all positions could be obtained by performing reactions in the 8-position first, in which Stille, Heck, Suzuki, and Sonogashira reactions gave good to excellent yields of product (63−98%). Stille and Heck reactions in the 6-position also gave the desired products in good yields (64−86%). The hydroxy group in the 3-position was activated as a triflate and used in productive Stille reactions (63−94%). This hydroxyl group was also used in O-alkylation reactions with different functionalized alkyl bromides (57−88%). The flavonoids, which are based on the chromone structure, and other related ring systems, have several interesting biological activities. The chromones ...