biostudies-literatureChellegui MUniversitat de ValènciaUniversité de NamurFonds De La Recherche Scientifique - FNRS32271-32283https://www.ebi.ac.uk/biostudies/studies/S-EPMC12415692biostudies-literatureUnknown15(39)In this contribution, Molecular Electron Density Theory (MEDT) is employed to investigate the (3 + 2) cycloaddition reaction between (<i>Z</i>)-<i>N</i>-methyl-<i>C</i>-(2-furyl)-nitrone 1 and but-2-ynedioic acid 2. DFT calculations at the M06-2X-D3/6-311+G(d,p) level of theory under solvent-free conditions at room temperature show that this reaction proceeds <i>via</i>CA3-Z diastereoselectivity, with the formation of the CA3-Z cycloadduct being both thermodynamically and kinetically more favoured than the CA4-Z one. Reactivity parameters obtained from CDFT calculations reveal that compound 1 predominantly behaves as a nucleophile with moderate electrophilic features, in contrast to compound 2, which demonstrates strong electrophilicity and limited nucleophilic ability. This disparity in eRSC advancesMEDT insights into the mechanism and selectivity of the (3 + 2) cycloaddition of (<i>Z</i>)-<i>N</i>-methyl-<i>C</i>-(2-furyl)-nitrone with but-2-ynedioic acid and the bioactivity of the reaction products.PMC12415692UV-INV-AE-3677056Mohammad-Salim HASalhi IBenmetir SBen Ahmed ABenhamed LChellegui MSalih RNde Julian-Ortize JVfalseMEDT insights into the mechanism and selectivity of the (3 + 2) cycloaddition of (<i>Z</i>)-<i>N</i>-methyl-<i>C</i>-(2-furyl)-nitrone with but-2-ynedioic acid and the bioactivity of the reaction products.In this contribution, Molecular Electron Density Theory (MEDT) is employed to investigate the (3 + 2) cycloaddition reaction between (<i>Z</i>)-<i>N</i>-methyl-<i>C</i>-(2-furyl)-nitrone 1 and but-2-ynedioic acid 2. DFT calculations at the M06-2X-D3/6-311+G(d,p) level of theory under solvent-free conditions at room temperature show that this reaction proceeds <i>via</i>CA3-Z diastereoselectivity, with the formation of the CA3-Z cycloadduct being both thermodynamically and kinetically more favoured than the CA4-Z one. Reactivity parameters obtained from CDFT calculations reveal that compound 1 predominantly behaves as a nucleophile with moderate electrophilic features, in contrast to compound 2, which demonstrates strong electrophilicity and limited nucleophilic ability. This disparity in e2025-01-01T00:00:00Z2025 Sep2026-06-02T02:26:19.982Z2026-04-13T03:11:47.597ZS-EPMC124156924092746610.1039/d5ra04143k