Despite the effectiveness of direct sulfation methods, the formation of complex sulfated molecules may be hampered the poor solubility of sulfated molecules in organic solvents, stability issues, and purification challenges of sulfated molecules. As a result, there was a growing interest in developing protection/deprotection strategy which involves the incorporation of sulfate group(s) in a masked form into the target scaffold followed by a deprotection step affording final sulfate molecules. [53] Simpson and co-workers have used alkyl protecting groups such as isobutyl and neopentyl groups for the preparation of several sulfate monoesters. In this method, phenolic or alcoholic substrates were initially treated with a strong base such as sodium hydride (NaH) or sodium hexamethyldisilazide (NaHMDS) in THF solvent at -75 °C followed by the addition of isobutyl or neopentyl chlorosulfate affording the desired protected sulfate monoesters. Subsequent deprotection step using sodium azide or sodium iodide affording the desired sulfates (Scheme 17). Scheme 17: Protection/deprotection method using the protected sulfate neopentyl or isobutyl esters followed by the deprotection reaction with NaN3 for the removal of neopentyl (nP) protecting group and sodium iodide (NaI) for the removal of isobutyl (iBu) protecting group affording the final desired sulfates. Scope of some sulfate monoester using protection/deprotection method.