Construction of Benzosultam‐Containing Fused‐ and Linked‐Biheterocycles by a Cascade Double Nucleophilic Cyclization

Abstract

Although nucleophilic aromatic substitution (SNAr) and many nucleophilic epoxide ring‐opening reactions proceed under similar anionic conditions, the literature examples of using these reactions in tandem for the construction of heterocyclic compounds are scarce. In this article, we disclose a detailed account of the synthesis of benzothiaoxazepine‐1,1‐dioxide‐containing fused‐ and linked‐biheterocycles by a base‐mediated, exo‐selective intramolecular epoxide‐opening/intramolecular nucleophilic aromatic substitution cascade of epoxide‐tethered ortho‐fluorobenzenesulfonamides. A wide range of substrates exhibited high overall yields and complete regio‐ and diastereoselectivity

Synthesis of benzimidazole-fused 1,4-benzoxazepines and benzosultams spiro-connected to a 2-oxindole core via a tandem epoxide-opening/SNAr approach

“…The ring-opening of epoxides, whether in simple transformations or in cascade reactions, constitutes a powerful tool for the elaboration of a diverse class of acyclic and (poly)cyclic compounds—ranging from simple primary alcohols to complex natural products. 8 Nucleophilic aromatic substitution (S N Ar) is another hallmark reaction widely used for arene functionalization. 9 Notably, S N Ar is the second most frequently-used transformation after amide bond formation reaction in medicinal chemistry.…”