Approach to regiochemistry using local softness in 1,3-dipolar cycloadditions

Abstract

The principle of hard and soft acids and bases is applied in the local sense to rationalize the regiochemistry in the cycloaddition reactions of a few typical 1,3-dipoles, in particular those with phosphorus-containing dipolarophiles. Local softnesses are calculated using density functional theory. It is observed that the regioselectivity can be explained using these new reactivity descriptors based solely on the properties of the reactants.

Effect of methanol on the regioselectivity and reaction rate of 1,3-dipolar cycloaddition of methyldiazoacetate to methyl acrylate and butene-1

“…As it may show from Eqs. (11) and (12), the form of the latter one simply assumes the same value of Koopman's defect for both HOMO and LUMO energies.…”

“…The latter terms were computed by the Koopman's theorem; see the Eqs. (11) and (12). The values of IP and EA, calculated according to all applied models of solvation, are resulted in the Table 2 thus allow to estimate influence of the environment.…”

“…The second approach is based on the theory of hard and soft acids and bases (HSAB) [8,9] as well as on the indices of local reactivity [10]. The last approach is successfully applied to prediction of preferable regio-isomers for various reactions of 1,3-dipolar cycloaddition [11][12][13][14] and allows to, at least, a semi-quantitative estimation of the stabilization energy of a dipole-dipolarophile couple at an early stage of reaction [15].…”

Use of Local Softness for the Interpretation of Reaction Mechanisms

“…For example, 1,3-dipolar cycloaddition reactions between various dipoles and dipolarophiles [30][31][32], excited state cycloadditions [33], and [4+2] Diels-Alder reactions [34] were studied recently by using local reactivity descriptors. However, in order to explain the regiochemistry of a multicenter reaction, such as cycloaddition, apart from the local softness one also needs to consider HSAB principle in a local sense.…”

“…In our group, intensive attempts have been made to apply local softness for the interpretation of the observed regiochemistry in various cycloaddition reactions between a 1,3-dipole (C=D=E, henceforth referred to as 13DP) and a dipolarophile (A=B, hereafter referred to as DPh) [31,37]. These 1,3-dipolar cycloaddition (13DC) reactions are important in synthetic organic chemistry due to the potential of forming many starting materials for the syntheses of heterocycles.…”