Mono-N-Alkylation of Sulfonamides with Alcohols Catalyzed by Iridium N-Heterocyclic Carbene-Phosphine Complexes

A N-heterocyclic carbene-phosphine iridium complex is presented for the efficient and selective mono-N-alkylation of sulfonamides with alcohols based on a borrowing hydrogenation strategy. Herein, water is the only by-product and this methodology thus offers a more environmentally benign and interesting alternative to the use of traditional alkylating reagents. This facile protocol tolerates a large number of (hetero) aromatic and aliphatic sulfonamides as well as (hetero) aromatic and aliphatic alcohols to obtain the desired product is high isolated yield (up to 98%). The alkylation completely retards after the formation of the secondary sulfonamide and no over-alkylation was observed in all cases. The option to run the reaction under solvent-free conditions as well as the scalability of this borrowing hydrogenation are key features of this protocol.

Automated summary

In this study, an efficient and selective mono-N-alkylation method for sulfonamides was developed based on a borrowing hydrogenation strategy. The use of water as the only by-product makes this method more environmentally friendly, and it shows good tolerance towards various types of sulfonamides and alcohols.