A Facile and Mild Alkylation Protocol of NH-Diphenyl Sulfondiimines

Abstract

As a promising pharmacophore, sulfondiimines have drawn increasing attention in recent years, but their uptake in medicinal chemistry is jeopardized by the scarcity of related transformations. Herein, we report a facile and mild N-alkylation protocol of NH-diphenyl sulfondiimines with alkyl halides to prepare a myriad of N-alkylated diphenyl sulfondiimines. Owing to air atmosphere, room temperature, as well as mild reaction conditions, this protocol has exhibited great potential in organic synthesis and medicinal chemistry by the late-stage functionalization of natural products.

Photocatalytic N-Alkylation of NH-Diaryl Sulfondiimines via Anti-Markovnikov Hydroamination with Styrenes

“…In 2014, the Bolm group utilized the “KOH/DMSO” superbase system to facilitate the S N 2 reaction of N H-sulfondiimines under an argon atmosphere (Scheme b) . Recently, our group developed a mild N -alkylation of N H-diphenyl sulfondiimines enabled by Cs 2 CO 3 in acetone under open-flask conditions (Scheme c) . However, these methods cannot be applied to introduce secondary or tertiary alkyl substituents due to the nature of the S N 2 strategy.…”

“…To overcome the limitations of previous methods, − we were intrigued by photocatalytic anti-Markovnikov hydroamination developed by the Nicewicz and Knowles groups, as well as others, which features mild and environmentally benign conditions, cheap and bulk styrenes as alkylating reagents, and a wide substrate scope covering primary, secondary, and even tertiary alkyl substituents . Herein, we report a facile and mild photocatalytic anti-Markovnikov hydroamination of N H-diaryl sulfondiimines with styrenes to synthesize N -alkylated sulfondiimines (Scheme d).…”

“…Furthermore, the photocatalytic alkylation operated smoothly with trisubstituted styrenes ( 2m and 2n ), and the intended products 3am and 3an were obtained with a high level of regioselectivity probably due to the relative stability of the corresponding dystonic styrene radical cations. It is worth noting that 3an was generated with a formation of a quaternary carbon center, which cannot be accessed by the traditional S N 2 strategies, − highlighting the breadth and expediency of this procedure.…”