Thermal azide–alkene cycloaddition reactions: straightforward multi-gram access to Δ²-1,2,3-triazolines in deep eutectic solvents

Abstract

Straightforward preparation of 1,2,3-triazolines in Deep Eutectic Solvents.

Cycloaddition Reactions of Azides and Electron‐Deficient Alkenes in Deep Eutectic Solvents: Pyrazolines, Aziridines and Other Surprises

“…Furthermore, the reaction times can be dramatically reduced in DES since higher temperatures than in the previously reported solvents (typically MeOH or toluene) are now possible. This is most probably due to a stabilising effect of the solvent on the transient triazolines, which minimises undesired decomposition and promotes the formation of cycloadducts . Most remarkably, previous reports in organic solvents used basic conditions to promote the formation of pyrazolines, but in contrast, our DFT calculations points to formal acidic media (a combination of H + and Cl − ) as key for this reaction in DES.…”

“…We previously reported that such transition states could lead to the formation of either an aziridine or an imine derivative. An alternative retro‐cycloaddition to a diazo compound and an imine ( TS2 3 , Scheme ) is a non‐productive but non‐competitive pathway (ΔΔG ≠ 333 =31.3 kcal/mol).…”

“…Our previously reported calculations showed that aziridines 4 were solely formed from 1,4‐disubstituted triazolines after the electrocyclic ring closure of a singlet biradical intermediate. Enaminones 8 nd would be formed from 3 nd′ or 3 nd through similar intermediate after a 1,2‐hydride (or acyl) shift and tautomerisation …”

“…A reliable access to pyrazolines from easily accessible azides and alkenes would provide a convenient alternative to established routes to these heterocycles, namely the cyclisation under acidic conditions of hydrazones generated from α,β‐unsaturated aldehydes or ketones and hydrazines, or the 1,3‐dipolar cycloaddition of electron‐rich nitrilimines and electron‐deficient alkenes . We recently reported the cycloaddition of azides and relatively electron‐rich alkenes in a deep eutectic solvent (DES) composed of choline chloride and urea . This strategy allowed the isolation of Δ 2 ‐triazolines on a gram scale, whilst minimising the use of volatile organic solvents.…”

Recent Developments on 1,3-Dipolar Cycloaddition Reactions by Catalysis in Green Solvents

“…In 2018, Sebest and co-workers developed a synthetic procedure to form 1,2,3-triazolines 76 by direct 1,3-dipolar azide-alkene cycloaddition reaction in a series of DESs (Scheme 14) [59].…”