Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

Abstract

The contribution to the energy barrier of a series of tethers in transannular cycloadditions of cycloalkenes with hydrazones has been computationally studied by using DFT. The Houk's distortion model has been employed to evaluate the influence of the tether in the cycloaddition reaction. That model has been extended to determine the contribution of each tether and, more importantly, the effect exerted between them. In addition to the distortion induced by the tethers, the entropy effects caused by them has also been studied. The analysis of the evolution of the electron localization function along the reaction revealed the highly concerted character of the reaction.

Keywords: DFT; distortion model; hydrazones; transannular cycloadditions.

Scheme 1

Experimental data (series a–d, k) and non-studied examples (series e–j) for transannular cycloadditions of cycloalkenone hydrazones.

Figure 1

Optimized (m062x/6-31G(d)) geometries for the transition structures of series a–f.

Figure 2

Top: Cycloaddition of protonated hydrazones as inverse-demand reaction of cycloaddition of azomethine imines. Bottom: molecular orbitals involved in the reaction and energy diagram of the reactivity of ethylene with azomethine imine and protonated hydrazone. Energy (eV) of molecular orbitals has been calculated at the m062x/6-311+G(d,p)/SMD=toluene level of theory.

Figure 3

Global electron density transfer (GEDT). Dashed black line indicates both TS.

Figure 4

ELF analysis for the reaction of series b leading to a system 6-6. Black trace corresponds to IRC. Colored dotted traces refer to lone pairs (monosynaptic basins) and colored plain traces to bonds (disynaptic basins). The vertical red line indicates the transition state (see Supporting Information File 1 for the full data).

Figure 5

Quantitative NCI analysis [36] for the reaction of series a–f leading to fused cyclohexanes. The resulting system is given in square brackets. In parentheses the integration over the volumes of −λ²·ρ² representing the total integration data corresponding to the weak noncovalent van der Waals interactions (represented in green). Higher forces like H-bonds are indicated as blue discs. In red unfavorable interactions are represented.

Figure 6

(a) Transannular cycloadditons of compounds 1a–k. (b) Houk’s distortion model applied to the reactions. TS2-a and TS2-b have been calculated separately. (c) and (d) Model reactions with tether A and B, respectively, to be subjected to the Houk’s distortion model, too. Compounds 7a–c and 9a–d have not been calculated because they are not relevant for the distortion analysis.

Scheme 2

Reaction with simple models.