Catalytic Hydroxycyclopropanol Ring-Opening Carbonylative Lactonization to Fused Bicyclic Lactones

A novel palladium-catalyzed ring opening carbonylative lactonization of readily available hydroxycyclopropanols was developed to efficiently synthesize tetrahydrofuran (THF) or tetrahydropyran (THP)-fused bicyclic γ-lactones, two privileged scaffolds often found in natural products. The reaction features mild reaction conditions, good functional group tolerability, and scalability. Its application was demonstrated in a short total synthesis of (±)-paeonilide. The fused bicyclic γ-lactone products can be easily diversified to other medicinally important scaffolds, which further broadens the application of this new carbonylation method.本研究开发了一种以易得的羟基环丙醇类化合物为底物的新型钯催化开环羰基化内酯化方法，可高效合成四氢呋喃（tetrahydrofuran, THF）或四氢吡喃（tetrahydropyran, THP）稠合的双环γ-内酯，这两类均为天然产物中常见的优势骨架。该反应具备反应条件温和、官能团耐受性优异、可放大性强的特点。研究通过(±)-芍药内酯（paeonilide）的简短全合成验证了该方法的应用价值。所得稠合双环γ-内酯产物可便捷衍生为其他具有药用价值的骨架，进一步拓宽了该新型羰基化方法的应用范围。