Abstract A “stop-and-flow” strategy was developed for the chemoselective dioxygenation of alkenes with a PIFA-initiated cyclization. This method is conceived for the desymmetrization of seco-diene, and a series of substituted 5-hydroxymethyl-γ-lactones were constructed after hydrolysis. This strategy also differentiates terminally substituted alkenes and constitutes a potentially novel synthetic approach for the efficient synthesis toward velbanamine.