Ring Expansion Strategies for the Synthesis of Medium Sized Ring and Macrocyclic Sulfonamides

Abstract

Two new ring expansion strategies are reported for the synthesis of medium sized ring and macrocyclic sulfonamides. Both methods can be performed without using classical protecting groups, with the key ring expansion step initiated by nitro reduction and amine conjugate addition respectively. Each method can be used to make diversely functionalised cyclic sulfonamides in good to excellent yields, in a range of ring sizes. The ring size dependency of the synthetic reactions is in good agreement with the outcomes modelled by Density Functional Theory calculations.

Instant Macrocyclizations via Multicomponent Reactions

“…43 Of particular interest is how to gain access to difficult medium-sized rings and macrocycles. 8,44 ■ RESULTS AND DISCUSSION Hence, we envisioned installing an -OTs functional group on an isocyanide MCR (IMCR)-based scaffold that would serve as the hub for an intramolecular aliphatic nucleophilic substitution (S N ) (Figure 2A). One of the most versatile building blocks in the MCR universe is the isocyanide moiety.…”

“…Indeed, over the last five years, MCR chemistry has emerged as an alternative and very effective synthetic strategy for the synthesis of different sizes of artificial macrocycles. ,, Moreover, peptide multicomponent macrocyclization has been designated as a strategy able to compete with the classic peptide cyclization. , Very recently, we classified the diverse macrocyclization tactics via MCR chemistry. , Based on the pioneer work of Zhu, Yudin, Wessjohann and Rivera, we identified all the strategies, underlining the importance of introducing more synthetic approaches by which the installation of orthogonal functional groups on a primary MCR-based adduct could lead to effective macrocyclization at a secondary level . Of particular interest is how to gain access to difficult medium-sized rings and macrocycles. , …”

Synthesis and Conformational Analyses of Cyclonucleoside Having 13-Membered Ring Bridging Nucleobase and 5′-Position via a Linker Containing Sulfonamide

“…Reduction of the azide group led to the formation of a 13-membered ring. The sulfonyltriazole structure was stable during purification and storage and would be useful as a sulfonylating agent for the preparation of other compounds such as sulfonamide-macrocycles. , …”

Ring expansion reactions of PO-containing molecules

“…Synthetic studies started by exploring amine-based substrates of the type 5a ; our previous work showed that related ring expansions are generally faster, more exergonic and higher yielding using amine side chains compared with alcohol- 11 or thiol-based systems. 12 A Conjugate Addition/Ring Expansion (CARE) 13 cascade was devised, with phosphonamidate derivative 9 reacted with different nucleophilic primary amines (Scheme 2A). The first part of the CARE cascade reaction proceeded as expected, with amine conjugate addition taking place in each case to form amines 10a – f in good yields.…”