The [3 + 2] cycloaddition (32CA) reaction between nitrones and ketenes has been studied within the Molecular Electron Density Theory (MEDT) at the Density Functional Theory (DFT) MPWB1K/6-311G(d,p) computational level. Analysis of the conceptual DFT reactivity indices allows the explanation of the reactivity, and the chemo- and regioselectivity experimentally observed. The particular mechanism of this 32CA reaction involving low electrophilic ketenes has been elucidated by using a bonding evolution theory (BET) study. It is determined that this reaction takes place in one kinetic step only but in a non-concerted manner since two stages are clearly identified. Indeed, the formation of the second C-O bond begins when the first O-C bond is already formed. This study has also been applied to predict the reactivity of nitrones with highly electrophilic ketenes. Interestingly, this study predicts a switch to a two-step mechanism due to the higher polar character of this zw-type 32CA reaction. In both cases, BET supports the non-concerted nature of the 32CA reactions between nitrones and ketenes.

Oxime–nitrone tautomerism takes place through a biomolecular mechanism. Participation of nitrone tautomer in nucleophilic addition reactions is evidenced by the first time.

A nickel-catalyzed reductive amidation of unactivated esters was recently reported, employing readily available and low-cost nitroarenes as nitrogen sources. Here we describe a comprehensive experimental and computational study, which reveals an intricate mechanism of this process. The reaction profile indicated azoarene as the terminal nitrogen intermediate formed from reduction of nitroarene. The activation of azoarene en route to amidation was probed by kinetics, Hammett plots, and DFT calculations. The activation likely involves Ni-catalyzed, ZnCl2promoted, reductive cleavage of the N=N double bond in an azoarene to form a bridging imido species, which then reacts in a rate-determining step with an ester to give an amide. Besides the nickel catalyst, ZnCl2 has an important influence in the rates and orders of the reaction. DFT computations suggest ZnCl2 stabilizes many of the intermediates in the reaction pathway of

Enantioenriched amino acids are produced in a hydrolytic kinetic resolution of racemic aminonitriles mediated by chiral pentose sugars. Experimental kinetic and spectroscopic results combined with DFT computational studies and microkinetic modeling help to identify the nature of the intermediate species and provide insight into the stereoselectivity of their hydrolysis in the prebiotically relevant ribose–alanine system. These studies support a synergistic role for sugars and amino acids in the emergence of homochirality in biological molecules.

A highly efficient and enantioselective asymmetric hydrogenation catalyzed by Ru-DTBM-segphos is reported for a broad range of pyridine−pyrroline trisubstituted alkenes. Kinetic, spectroscopic, and computational studies suggest that addition of H 2 is rate-determining, alkene insertion is enantio-determining, and that the presence and position of the pyridine nitrogen is critical to enantioselectivity. These studies also reveal an intriguing Ru-catalyzed H/D exchange process that is facilitated by a substrate at room temperature and low pressure, where hydrogenation activity is suppressed. These studies lead to a mechanistic proposal that further defines the roles of hydrogen gas, Ru−H species, and protic solvents in this catalytic system.

In a recent study, a new procedure for Z-selective olefin synthesis by reductive coupling of alkyl iodides with terminal alkynes in the presence of iron salts is described. This transformation is representative of many newly developed synthetic routes through the involvement of multiple species and phases, which makes mechanistic insight hard to obtain. Here, we report computational work aimed at exploring the possible reaction pathways. DFT calculations lead to two suggested routes, one involving C−I reduction by metallic zinc and radical addition to the alkyne and the other involving addition of two reduced iron species to the alkyne bond followed by reductive elimination. Comparison to experimental results as well as kinetic modeling is used to discuss the likelihood of these and related mechanisms.

Mechanistic studies of the Cu-catalyzed C−N coupling of sterically hindered aryl iodides with sterically hindered anilines are carried out to shed light on how a recently reported pyrrol-ol ligand affects the reaction. Kinetic, spectroscopic, and computational tools help to probe the nature of the active catalyst species and the rate-determining step in the cycle. In contrast to most known Cu systems, oxidative addition is found to precede coordination of the amine. These studies help to design an efficient process under mild conditions using a fully homogeneous system as well as protocols that enable high yields by temperature scanning and controlled addition of the base. The insights obtained for the XX-type ligand may lead to a general approach for challenging substrate classes in Cu-catalyzed coupling reactions.

The mechanism of cycloaddition reactions of nitrones with isocyanates has been studied using density functional theory (DFT) methods at the M06-2X/cc-pVTZ level of theory. The exploration of the potential energy surfaces associated with two reactive channels leading to 1,2,4-oxadiazolidin-5-ones and 1,4,2-dioxazolidines revealed that the cycloaddition reaction takes place through a concerted mechanism in gas phase and in apolar solvents but a stepwise mechanism in polar solvents. In stepwise mechanisms, the first step of the reaction is a rare case in which the nitrone oxygen acts as a nucleophile by attacking the central carbon atom of the isocyanate (interacting with the π-system of the C═O bond) to give an intermediate. The corresponding transition structure is stabilized by an attractive electrostatic interaction favored in a polar medium. The second step of the reaction is the rate-limiting one in which the formation of 1,2,4-oxadiazolidin-5-ones or 1,4,2-dioxazolidines is decided. Calculations indicate that formation of 1,2,4-oxadiazolidin-5-ones is favored both kinetically and thermodynamically independently of the solvent, in agreement with experimental observations. Noncovalent interactions (NCI) and topological analysis of the gradient field of electron localization function (ELF) bonding confirmed the observed interactions.