Modular Synthesis of [6,6]-Oxaspirolactones Enabled by Palladium-Catalyzed Carbonylative Spirolactonization

An expedient and efficient carbonylative protocol proceeded via palladium-catalyzed tandem cyclic ketonization and carbonylative spirolactonization has been developed. This carbonylation reaction is compatible with a wide range of hydroxyalkyl ketone tethered benzyl chlorides bearing different functional groups and can be proceeded under comericially available Pd2(dba)3/BINAP catalyst system, providing a straithfowrd and practical approach to a broad range of [6,6]-oxaspirolactones. The synthesized [6,6]-oxaspirolactones are commonly found as core structures in natural products and can potentially serve as C2-symmetric ligand synthons. A new palladium-catalyzed tandem carbonylative spirolactonization reaction utilizes benzyl chlorides tethered hydroxyalkyl ketones and CO substrates, enabling efficient synthesis of diverse [6,6]-oxaspirolactones. The straightforward protocol ensures high atom economy and compatibility with various functional groups. Under optimized conditions, over 20 examples of the desired product are obtained. image