A self-immolative bioorthogonal conditionally cleavable linker based on Grob fragmentation is described. It is derived from 1,3-aminocyclohexanols and allows the release of sulfonate-containing compounds in aqueous media. Modulation of the amine pKa promotes fragmentation even at slightly acidic pH, a common feature of several tumor environments. The Grob fragmentation can also occur under physiological conditions in living cells, highlighting the potential bioorthogonal applicability of this reaction.