Development of Synthetic Approaches to Biaryl Sultams via CH Functionalization

Abstract

Biaryl sultams represent a privileged molecular scaffold in drug discovery owing to their potential as a clinical candidate. Various developments toward the synthesis of diverse biaryl sultams including metal‐catalyzed and metal‐free CH functionalization involving CC/CN bond formation or annulative cyclization have been advanced in recent time. However, a transition metal‐catalyzed direct CH functionalization approach remains a powerful variant and has been utilized tremendously for the past several decades. The postsynthetic transformations of biaryl sultams to drug‐like molecules offer a tremendous possibility in drug discovery. In this article, we aim to provide an overview of various developments made in the synthetic approaches to biaryl sultams via CH functionalization, with a futuristic emphasis on their postsynthetic utility in accessing (hetero)biaryls containing an ortho ‐sulfonamide or amine functionality, a promising and potentially useful molecular scaffold in therapeutic discovery. The current challenges and a future perspective are also discussed briefly.

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

“…Based on the literature [ 15 – 16 ], our previous experience [ 14 , 17 – 18 ], and current understanding, a plausible mechanism for the benzylic oxidation is depicted in Scheme 5 . Initially, a sulfate radical anion (SO 4 ·− ) is generated by homolytic cleavage of the peroxy linkage under heating conditions [ 17 ].…”

Substituent-Controlled Regioselective Photoinduced Cyclization of N-Allylbenzamides with N-Sulfonylaminopyridinium Salts

“…There have several successful routes developed for the synthesis of benzosultams, including the transition-metal or Lewis acid-catalyzed intramolecular cyclizations, as well as the intermolecular synthetic strategies . Recently, direct C–H functionalization, which can avoid the prefunctionalization of starting materials, was developed for the synthesis of benzosultams . For example, transition-metal-catalyzed C–H annulations of sulfonamides with alkynes, arynes, and allenes were developed (Scheme a) .…”