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

Abstract

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.

Triflamides and Triflimides: Synthesis and Applications

“…Triflamide derivatives 166 containing a 3-benzazepine moiety can be used to treat Alzheimer's disease [155]. It should be noted that the synthesis of the N-alkyl-substituted triflamides presented in the scheme above is carried out by the reaction of TfNH 2 with the corresponding alcohol in the presence of Cs 2 CO 3 and an Ir-centered catalyst [156]. Such substituted sulfonamides exhibit a number of different types of biological activity (e.g., anti-inflammatory activity) [156].…”