DFT Investigation of the Mechanism ofE/ZIsomerization of Nitrones

Abstract

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.

Copper‐Catalyzed Carbonyl Group Controlled Coupling of Isatin Oximes with Arylboronic Acids To Prepare N‐Aryloxindole Nitrones

“…[14] The (E)/(Z) configuration of nitrones have often been used to rationalize the stereoselectivity of important 1,3-dipolar cycloaddition reactions. [15] Exploring efficient methods to selectively prepare (E)/(Z) isomers of nitrones is desirable, and, therefore, we investigated the coupling of isatin oximes with arylboronic acids to examine the matters in question above. Herein, we report a general and scalable carbonyl group controlled strategy for the N-arylation of N-unprotected isatin oximes with arylboronic acids to prepare (E)-N-aryloxindole nitrones (Scheme 1D).…”

Organocatalytic Enantioselective Synthesis of Trifluoromethyl‐Containing Tetralin Derivatives by Sequential (Hetero)Michael Reaction–Intramolecular Nitrone Cycloaddition

“…The cycloaddition reaction was studied at B3LYP‐D3BJ/Def2SVP level of theory to calculate geometries and then single point calculations at B3LYP‐D3BJ/Def2TZVP/PCM=toluene level of theory were performed (for details see the Supporting Information). E / Z Isomerization of nitrones has been considered since the difference was in the range of 20–30 kcal mol −1 , compatible with the reaction conditions. Four approaches can be defined for each nitrone, thus a total of eight approaches leading to four different compounds have been studied (Scheme ).…”

Nitrone Directing Groups in Rhodium(III)‐Catalyzed C−H Activation of Arenes: 1,3‐Dipoles versus Traceless Directing Groups

“…Occasionally variations of the substituent in either substrate led to formation of two diastereomeric products ( 6 va – 6 ac ). The observation of two such products seems to suggest that the dipolar addition either followed a stepwise mechanism or a Z / E isomerization of the nitrone might be involved …”