Synthesis of selected plant metabolites of icafolin–methyl via the formation of a spirocyclic nitronate

A scalable and diastereoselective synthesis of four icafolin-methyl plant metabolites bearing a 4-hydroxy-2-isoxazoline scaffold is described. The key to success was a practical cyclocondensation of 3,5-difluoronitromethane with α-formylbutyrolactone and a multigram-scale Grieco dehydration protocol, performed in continuous flow.