Quantum Mechanical Elucidation on [3+2] cycloaddition reaction of aryl nitrile oxide with cyclopentenones.

The [3 + 2] cycloaddition (32CA) reaction of benzonitrile oxide (BNO) with 4-substituted 4-hydroxy-2-cyclopentenone has been investigated using molecular electron density theory (MEDT) at the Density Functional Theory (DFT) B3LYP/6-31G (d), M06/6-311G (d,p) and M06-2X/6-311++G (d,p) levels. The present theoretical computations indicate that the reaction of BNO with 4-substituted 4-hydroxy-2-cyclopentenones is via [3 + 2] cycloaddition, where the three atom component (TAC) chemo-selectively adds across the alkene functionality in the 2-cyclopentenones (Path A). Analysis of the electrophilic PA+ and nucleophilic PA- Parr functions at the different reaction sites in the alkene counterpart indicates that the aryl nitrile oxides add across the atomic centers with the highest Mulliken atomic spin densities. The results reported in this study are in good agreement with previous experimental work. The GEDT calculations unravel the low polar character of the [3 + 2] cycloaddition reactions. This reaction occurs with poor enantioselectivity, but a high degree of stereo-, peri-, diastereo, and regioselectivity is seen for the reaction of the BNO with 4-hydroxy-4-methyl-2-cyclopentenones. The regioselectivity of the reactions is the same in all the solvents investigated.

A DFT mechanistic study on oxidative dehydrogenative Diels-Alder reaction of alkylbenzenes.

Cross-dehydrogenative Diels-Alder cycloaddition reaction between readily-available alkyl benzenes and electron-deficient dienophiles is an attractive synthetic route to access carbocyclic compounds which have high utility in the chemical and pharmaceutical industries. This work reports a study at the M06-2X/6-311G(d) and M06-2X/6-311++G(d,p) levels of theory on the reaction of alkyl benzenes with electron-deficient dienophiles in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as an oxidant and hydroquinone as an activator, so as to understand the chemoselectivity of the reaction (addition across the alkene functionality versus the ketone functionality), the role of the activator, the effects of substituents and the effect of solvent on the reaction. The results show the addition of the alkene bonds of methylstyrene across the alkene functionality of the electron-deficient dienophiles has generally low barriers compared to the addition across the carbonyl functionality of the electron-deficient dienophile. Powerful electron-withdrawing group (cyano) on the electron-deficient dienophile decrease the energy barrier for the cycloaddition and decrease the stability of the product whiles weak electron-withdrawing (bromine and chlorine) and electron-donating groups increase the energy barrier for the cycloaddition and decrease the stability of the product. The hydroquinone as an activator decreases the activation barrier for the Diels-Alder cycloaddition reaction.