Synthetic methods inspired by Nature often offer unique advantages including mild conditions and biocompatibility with aqueous media. Inspired by an ergothioneine biosynthesis protein EgtB, a mononuclear non-haem iron enzyme capable of catalysing the C-S bond formation and sulfoxidation, herein, we discovered a mild and metal-free C-H sulfenylation/intramolecular rearrangement cascade reaction employing an internally oxidizing O-N bond as a directing group. Our strategy accommodates a variety of oxyamines with good site selectivity and intrinsic oxidative properties. Combining an O-N bond with an X-S bond generates a C-S bond and an S=N bond rapidly. The newly discovered cascade reaction showed excellent chemoselectivity and a wide substrate scope for both oxyamines and sulfenylation reagents. We demonstrated the biocompatibility of the C-S bond coupling reaction by applying a coumarin-based fluorogenic probe in bacterial lysates. Finally, the C-S bond coupling reaction enabled the first fluorogenic formation of phospholipids, which self-assembled to fluorescent vesicles in situ.