No abstract

Computational calculations based on experimental results shed light on the mechanistic proposal for a Friedel-Crafts alkylation reaction between indole and nitroalkenes, catalysed by a chiral aminoindanol-derived thiourea. In our hypothesis both substrates are simultaneously coordinated to the catalyst in a bifunctional mode. This study elucidates the crucial role played by the hydroxyl group of the catalyst in the success of the reaction. The OH group seems to be involved in the preferential attack of the indole over the nitroalkene, affording the major enantiomer and stabilizing the resulting transition state by a concomitant coordination with the nitroolefin. The results obtained with other catalysts from the same family, and other indoles, are reported and discussed. Theoretical calculations are in agreement with the experimental outcomes and with our previously developed mechanism, displaying the pivotal role played by hydrogen bond interactions.

The mechanism of the reaction between nitrones and lithium ynolates has been studied using DFT methods at the M06-2X/cc-pVTZ/PCM=THF level. After the formation of a starting complex an without energy barrier, in which the lithium atom is coordinated to both nitrone and ynolate, the reaction takes place in one single kinetic step through a single transition structure. However, the formation of C-C and C-O bonds takes place sequentially through a typical two-stage, one-step process. A combined study of noncovalent interactions (NCIs) and electron localization function (ELFs) of selected points along the intrinsic reaction coordinate (IRC) of the reaction confirmed that, in the transition structure, only the C-C bond is being formed to some extent, whereas an electrostatic interaction is present between carbon and oxygen atoms previous to the formation of the C-O bond. Indeed, the formation of the second C-O bond only begins when the first C-C bond is completely formed without formation of any intermediate. Once the C-C bond is formed and before the C-O bond formation starts the RMS gradient norm dips, approaching but not reaching 0, giving rise to a hidden intermediate.

The synthesis, characterization, and evaluation of a new highly efficient organocatalyst, namely, (5S)‐2,2,3‐trimethyl‐5‐thiobenzylmethyl‐4‐imidazolidinone hydrochloride, has been achieved. The catalyst possesses important structural features that should increase the catalytic efficiency and solubility in polar media. The application of the ionic‐liquid‐supported imidazolidinone catalyst in enantioselective Diels–Alder reactions was investigated. The Diels–Alder reactions of several dienes and dienophiles proceeded efficiently in the presence of the catalyst to provide the desired products in moderate to good yields and from good to excellent enantioselectivities. The conformation study confirms that in the transition state the Re face is shielded completely by the phenyl ring and an approach on the less hindered Si face is preferred. Particularly remarkable is the fact that the entire ionic liquid/HCl 0.01 M/catalyst system can be recovered and reused in up to six runs without an appreciable loss of catalytic activity.

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

The hitherto unknown mechanism of E/Z isomerization of nitrones, with important implications in 1,3-dipolar cycloaddition chemistry, has been investigated using density functional theory calculations. Unimolecular and bimolecular processes have also been considered. Both concerted and stepwise mechanisms involving either zwitterionic or diradical species have been studied. The unimolecular torsional mechanism and isomerization through intermediate oxaziridines present energy barriers too high to justify the observed experimental results. Several bimolecular processes involving an initial dimerization are possible. Among them, the concerted process can be discarded in terms of energy barrier. Zwitterionic intermediates are too high in energy to be considered. From the two possible diradical approaches consisting of either C-O or C-C coupling, the latter is the most favored. Thus, the mechanism of E/Z isomerization of nitrones proceeds via a diradical bimolecular process involving an initial dimerization through a C-C coupling followed by a dedimerization, with energy barriers for the rate-limiting step of 29.9 kcal/mol for C-methyl nitrones and 25.8 kcal/mol for C-(methoxycarbonyl) nitrones. These values are in very good agreement with the experimental data previously measured through kinetic experiments.

The mechanism of the addition of lithium enolates derived from esters, ketones and aldehydes to nitrones (Mannich‐type reaction) has been studied using DFT methods. While the reactions with α‐methoxy and α‐methyl enolates takes place through a stepwise mechanism, consisting of an initial nucleophilic attack of the enolate to the nitrone carbon followed by a second nucleophilic attack of the nitrone oxygen to the formed carbonyl group, the reaction with α‐unsusbtituted enolates takes place through a one‐step mechanism. The IRC analysis shows the presence of a hidden intermediate in agreement with one kinetic step two stages process. The topological analysis of the electronic localization function (ELF) confirms that only when the first C–C bond is formed, does the C–O bond formation begin. The NCI analyses, are also in agreement with the formation of intermediates for α‐methoxy and α‐methyl enolates and a highly asynchronous one‐step process in the case of α‐unsusbtituted enolates.

Various α‐hydrazido phosphonates have been easily prepared on the basis of the nucleophilic addition of diphenyl phosphite to reactive, preformed N‐acylhydrazones and a three‐component (aldehydes, N‐benzoylhydrazide and diphenyl phosphite) coupling reaction through a non‐catalyzed process. An unprecedented and promising enantioselective example of this reaction is also reported.