Palladium-catalyzed Asymmetric Allylic C-H Oxidation For The Formal Synthesis Of Gonytolide C

Chroman compounds containing benzodihydropyran core structure are a class of natural products exhibiting important biological activities,such as antibacterial and antifungal.The family of Gonytolides with the structure of butyl lactone and chromanone are the representatives of this kind of natural products.They are isolated from fungi and have a significant effect of promoting the innate immune response.In addition,they show antibacterial and cytotoxic activities.Because of the important biological activities of these compounds,many articles have described asymmetric catalytic synthesis of such natural products.Recently,our group accomplished an enantioselective intramolecular allylic C-H oxidation to generate optically active chromans under the cooperative catalysis of a palladium complex of chiral phosphoramidite ligand and 2-fluorobenzoic acid,by using benzoquinone compounds as an oxidant.We have successfully applied this method to construct the key structure of Gonytolide C.Then we tried several routes to build up the skeleton of benzodihydropyran by using epoxidation,photoreaction,lactone cyclization promoted by selenium and bromide and dihydroxylation,however,only dihydroxylation reaction allows for a successful synthetic route to access the target molecule.Finally,an asymmetric formal synthesis of Gonytolide C was accomplished in 92%ee.