Local Softness as a Regioselectivity Indicator in [4+2] Cycloaddition Reactions

Abstract

As part of our continuing interest in the connection between chemical reactivity and the HSAB principle, both globally and locally, we explored via 3-21 G calculations on local and global softness the statement made by Gazquez and Mendez. Their statement, claiming that two chemical species should react through atoms showing equal softness, has been precised to rationalize the regioselectivity of Normal Electron Demand Diels−Alder reactions between terminally monosubstituted 1,3-butadienes and monosubstituted ethenes. In the presence of this substitution pattern, a head-to-head mode of cyclization is largely experimentally observed, also known as “ortho rule”. The closest values of the condensed local softness were found for the unsubstituted termini, thereby suggesting that these cycloadditions would proceed through an asynchronous pathway, as supported by transition state geometries reported by Houk et al.

Electrophilic behaviour of 3-methyl-2-methylthio-1,3,4-thiadiazolium salts: A multimodal theoretical approach

“…23 In a finite-differences approximation, the condensed Fukui functions for ionic reactions, α k f (with α = +,-) are obtained first by condensing the electronic density to the charge of each atom, k, in the molecule, and afterwards differentiating with respect to the total number of electrons (Eqs. 5,6):…”

5-(3-Phosphonated 1H-1,2,3-triazol-4-yl)isoxazolidines: synthesis, DFT studies and biological properties

“…Moreover, the electrophilicity differences between vinyl-triazole and nitrone (∆ω < 0.2 eV) indicate a lower polar character for these cycloadditions, and their values are characteristic of nonpolar pericyclic reactions. [38][39] Being the present 1,3-dipolar cycloaddition an inverse electron demand type process, the nitrone undergoes a nucleophilic attack by the vinyl-triazole; thus, the local properties to be used are reported in Table 3. For the dipolarophile, C4 has the higher local nucleophilicity index, ω-with respect to C5.…”

Use of Local Softness for the Interpretation of Reaction Mechanisms

“…For example, 1,3-dipolar cycloaddition reactions between various dipoles and dipolarophiles [30][31][32], excited state cycloadditions [33], and [4+2] Diels-Alder reactions [34] were studied recently by using local reactivity descriptors. However, in order to explain the regiochemistry of a multicenter reaction, such as cycloaddition, apart from the local softness one also needs to consider HSAB principle in a local sense.…”