A Sulfonative rearrangement of N-aryl sulfamates to para-sulfonyl anilines

The C(sp2)-aryl sulfonate functional group is widely found in bioactive scaffolds but can often only be accessed under forcing temperatures (>190 °C) and corrosive reaction conditions. Inspired by the Tyrer process to sulfa dyes that involves an aniline N(sp2)-SO3 intermediate en route to a C(sp2)-SO3 rearranged product - we deployed tributylsulfoammonium betaine (TBSAB) as an initiating mild sulfamating agent to sulfonate relay reagent. A range of aniline and heterocyclic scaffolds were sulfonated in high conversions (6 examples of N(sp2)-sulfamates up to 99% isolated yield and 16 examples of C(sp2)-sulfonate in up to 80% isolated yield) with the ability to change the ortho-para selectivity of the products obtained under thermal control. Isolation of the N(sp2)-SO3 intermediates for a two-step procedure was significantly lower yielding than a direct one-pot procedure. Furthermore, we explore counterion effects on the N- to C- sulfate rearrangement and discovered the reversibility of the TBSAB reagent. Investigation of the N- to C- mechanism through designed examples with variation at the heteroatom position, and kinetic isotope experiments (KIEH/D) confirmed the formation of a key N(sp2)-SO3 intermediate and further supporting evidence of an intermolecular mechanism. Compounds without an accessible nitrogen (or hydroxyl) lone pair did not undergo sulfonation under these reaction conditions.