Scandium(III)‐Triflate‐Catalyzed Multicomponent Reactions for the Synthesis of Nitrogen Heterocycles

Abstract

The need of understanding the interactions between small organic molecules and biological targets has stimulated the development of new methodologies for the synthesis of compounds with potential biological properties. In this scenario, multicomponent reactions have been considered as high atom‐efficient strategies which allow the generation of high levels of molecular diversity and complexity, using relatively simple and eco‐friendly experimental procedures. Among the plethora of catalysts used in multicomponent reactions, rare earth metal triflates, especially scandium(III) triflate [Sc(OTf)3], emerged as water‐resistant Lewis acids with remarkable catalytic activity in water‐containing environments. This review describes the recent progress on the use of scandium(III) triflate as Lewis acid catalyst for multicomponent reactions applied to the synthesis of nitrogen‐containing heterocycles, valuable privileged scaffolds in Organic and Medicinal Chemistry.

Substrate-Dependent Selectivity in Sc(OTf)3-Catalyzed Cyclization of Alkenoic Acids and N-Protected Alkenamides

“…These triflate salts feature an environmentally benign character, moderate cost and availability and retain their catalytic activity in the presence of a broad array of Lewis bases, thus exhibiting outstanding functional group tolerance. Among them, Sc(OTf) 3 has attracted particular attention due its additional advantages comprising high Lewis acidity, stability even towards hydrolysis (water-compatibility), remarkable catalytic activity and recycling ability [37][38][39]. With regard to these appealing features, it is surprising that rare-earth triflates and in particular Sc(OTf) 3 have never been investigated as sustainable catalysts to access γ/δ-lactone or -lactam scaffolds from alkenoic acids or alkenamides by hydrofunctionalization.…”

A Sc(OTf)3-catalyzed one-pot two-step approach for spiro-oxindole dihydropyridine derivatives initiated by N-olefination of MBH carbonates

“…10 However, these methods also suffer from one or more limitations, including air and moisture sensitivity, high temperatures, and low yields. As both the Meinwald rearrangement-involved cyclization and inverse-Electron-Demand Aza-Diels–Alder (iEDADA) reaction could be catalyzed by Lewis acids, 9,11 we herein proposed that epoxides might facilitate an iEDADA reaction with the in situ generated N -olefination product of isatin-derived MBH carbonates to afford various structurally important spiro-oxindole dihydropyridine derivatives.…”

Multicomponent Assembly of Trisubstituted Imidazoles and Their Photochemical Cyclization into Fused Polyheterocyclic Scaffolds

“…Multicomponent reactions (MCRs) constitute an attractive tool for a straightforward assembly of various nitrogen-containing heterocycles . This is particularly important considering that the majority of currently marketed drugs incorporate nitrogen-containing heterocyclic moiety as their core structural feature …”