Alkyl substitution α to the ketone of an allenyl vinyl ketone enhances Nazarov reactivity by inhibiting alternative pathways involving the allene moiety and through electron donation and/or steric hindrance. This substitution pattern also accelerates Nazarov cyclisation by increasing the population of the reactive conformer and by stabilising the oxyallyl cation intermediate. Furthermore, α substitution by an alkyl group does not alter the regioselectivity of interrupted Nazarov reactions when the oxyallyl cation intermediate is intercepted by addition of an oxygen nucleophile, or by [4+3] cyclisation with acyclic dienes. The regioselectivity of the Nazarov process for allenyl vinyl ketones was determined to be a result of an electronic bias in the oxyallyl cation intermediate. Computational data are consistent with this observation.

The use of mechanical stresses to induce chemical reactions has attracted significant interest in recent years. Computational modeling can play a significant role in developing a comprehensive understanding of the interplay between stresses and chemical reactivity. In this review, we discuss techniques for simulating chemical reactions occurring under mechanochemical conditions. The methods described are broadly divided into techniques that are appropriate for studying molecular mechanochemistry and those suited to modeling bulk mechanochemistry. In both cases, several different approaches are described and compared. Methods for examining molecular mechanochemistry are based on exploring the force-modified potential energy surface on which a molecule subjected to an external force moves. Meanwhile, it is suggested that condensed phase simulation methods typically used to study tribochemical reactions, i.e., those occurring in sliding contacts, can be adapted to study bulk mechanochemistry.

A variety of density functional theory (DFT) methods are paired with Pople basis sets of varying sizes and evaluated for use with organoselenium compounds. The ability of each method to predict reliable geometries and energies is determined through comparison with quadratic configuration interaction with single and double excitations (QCISD) results. The recommended procedure for accurate prediction of energies and geometries is to use the B3PW91 functional with the 6-311G(2df,p) basis set. The B3PW91/6-31G(d,p) level of theory gives almost identical geometries as larger basis sets, so geometries can be predicted at this level for computational efficiency.

The reaction mechanism for the reduction of hydrogen peroxide by N,N-dimethylbenzylamine diselenide, its selenol analogue, and the charged analogues of the diselenide and selenol are elucidated using reliable electronic structure techniques. It is found that the reaction using the diselenide has a large Gibbs energy barrier of 173.5 kJ/mol. The cationic diselenide, with both amines protonated, shows a lower barrier of 103.5 kJ/mol. Both diselenide species show significant Se-Se bond lengthening upon oxidation. An unusual two-step mechanism is found for the selenol with barriers of 136.3 and 141.9 kJ/mol, respectively, showing that it is unlikely that the selenol is the active form. The zwitterion, selenolate, and protonated amine analogues of the selenol show one-step reactions with energy barriers of 82.7, 92.7, and 102.3 kJ/mol, respectively. The zwitterion of the selenol shows the most favorable reaction energies, which is in good agreement with proposed mechanisms for this reaction.

The reactivity of disulfide and diselenide derivatives towards F(-) and CN(-) nucleophiles has been investigated by means of B3PW91/6-311+G(2df,p) calculations. This theoretical survey shows that these processes, in contrast with the generally accepted view of disulfide and diselenide linkages, do not always lead to SS or SeSe bond cleavage. In fact, SS or SeSe bond fission is the most favorable process only when the substituents attached to the S or the Se atoms are not very electronegative. Highly electronegative substituents (X) strongly favor SX bond fission. This significant difference in the observed reactivity patterns is directly related to the change in the nature of the LUMO orbital of the disulfide or diselenide derivative as the electronegativity of the substituents increases. For weakly electronegative substituents, the LUMO is a σ-type SS (or SeSe) antibonding orbital, but as the electronegativity of the substituents increases the π-type SX antibonding orbital stabilizes and becomes the LUMO. The observed reactivity also changes with the nature of the nucleophile and with the S or Se atom that undergoes the nucleophilic attack in asymmetric disulfides and diselenides. The activation strain model provides interesting insights into these processes. There are significant similarities between the reactivity of disulfides and diselenides, although some dissimilarities are also observed, usually related to the different interaction energies between the fragments produced in the fragmentation process.