Solid-Phase Synthesis of Coumarins via ipso Substitution Reaction

Significance

Coumarins are important synthetic targets because of their bioactivities such as anti-cancer and anti-HIV. The authors demonstrated the solid-phase synthesis of 3-(5-arylpyridin-2-yl)-4-hydroxycoumarins 4 which are a synthetically challenging series of coumarin derivatives. Thus, resin-supported 2′-(5-bromo)pyridylacetates 1 reacted with arylboronic acids in the presence of Pd(PPh₃)₄ to give 2′-(5-aryl)pyridylacetates 2. Then, treatment of 2 with LDA at -78 °C followed by reaction with 2-bromobenzoyl chlorides gave the C-acylated products 3. Treatment of 3 in xylene gave the desired coumarins 4 (25-40% overall yield).