Cycloaddition of Benzonitrile Oxide to Acetonitrile, Propyne and Propene − A Comparative Theoretical Study of the Reaction Mechanism and Regioselectivity

Abstract

Quantum chemical calculations (MP2/6-31G* and B3LYP/6-31G*) were used to compare the reactivity, regioselectivity and orbital involvement of the reaction of benzonitrile oxide with the dipolarophiles acetonitrile, propyne and propene. All reactions are thermodynamically favoured. The product stability decreases in an order propyne Ͼ acetonitrile Ͼ propene, and reflects the degree of aromatic stabilisation of the product. The activation barriers depend strongly on the computational method used and decrease in the expected order of increasing reactivity (acetonitrile Ͼ propyne Ͼ propene) in the MP2 calculations, but are similar to each other when

An Analysis of the Regioselectivity of 1,3‐Dipolar Cycloaddition Reactions of Benzonitrile N‐Oxides Based on Global and Local Electrophilicity and Nucleophilicity Indices

“…[4] This method is fairly general and complements classical condensation methods because of its greater functional group compatibility and the use of milder The 13DC reactions of nitrile oxides have also been theoretically studied. [5][6][7][8] The regioselectivity of the 13DC reactions of benzonitrile N-oxides (NBOs) with ED alkynes and alkenes has been studied by Hu and Houk. [7] The transition-state structures (TSs) for the reactions of fulminic acid (1) and mesitonitrile oxide (2) and the ED methyl propiolate (3) and cyanoacetylene (4) have been studied at the B3LYP/6-31G* level of theory (see Scheme 2).…”

“…More recently, Wagner and co-workers [8] studied the 13DC reactions of benzonitrile oxide (9) with propene (10) and propyne (11) at the same level of theory (see Scheme 3). Note that the methyl group nucleophilically activates these π systems.…”

The 1,3-Dipolar Cycloaddition of Nitrile Oxide to Vinylacetic Acid: Computational Study of Transition States Selectivity, Solvent Effects, and Bicyclo Formation

“…In contrast to Diels-Alder reactions, which are known to be under kinetic control, 46,[78][79][80] it is not clear if 13DC reactions have kinetic control or thermodynamic control. 80 However, experimental 81 and theoretical 24,82 studies involving nitrile oxides point to mechanisms controlled in a kinetic way. Furthermore, it has also been reported that a preference for β face attack, which is more sterically hindered due to torsional factors (such as a preference for staggered conformations and for the concave face of the envelope conformation in cyclopentene rings) 83 has more relevance than steric factors and governs stereoselectivity in several cases.…”

“…18 From the pioneering work of Huisgen,19,20 who postulated the concerted reaction mechanism of cycloaddition reactions, this kind of reaction has been widely studied, both theoretically and experimentally. [21][22][23][24][25][26][27][28][29][30] The control of regioselectivity of 13DC has been explained by frontier molecular orbital (FMO) analysis. 2,3 In this treatment, the nucleophilicity and electrophilicity of the species are based on HOMO and LUMO energies and orbital coefficients.…”

“…These values are in the same order of magnitude obtained in the literature for similar reactions. 24,34,35,37,69 In fact, cycloadditions involving benzonitrile oxide proceed smoothly even with completely unactivated dipolarophiles, such as ethene, under ordinary laboratory conditions. 70 Considering the three functionals, the lowest activation free energies (26.2 -28.7 kcal mol -1 ) were obtained using PBE1PBE, while CAM-B3LYP and B3LYP produced very similar barriers (29.5 -32.2 kcal mol -1 ).…”