Symmetry‐Enthalpy Correlations in Diels–Alder Reactions

Abstract

Woodward-Hoffmann (WH) rules provide strict symmetry selection rules: when they are obeyed, a reaction proceeds; when they are not obeyed, there is no reaction. However, the voluminous experimental literature provides ample evidence that strict compliance to symmetry requirements is not an obstacle for a concerted reaction to proceed, and therefore the idea has developed that it is enough to have a certain degree of the required symmetry to have reactivity. Here we provide quantitative evidence of that link, and show that as one deviates from the desired symmetry, the enthalpy of activation increases, that is, we show that concerted reactions slow down the further they are from the ideal symmetry. Specifically, we study the deviation from mirror symmetry (evaluated with the continuous symmetry measure (CSM)) of the [4+2] carbon skeleton of the transition state of a series of twelve Diels-Alder reactions in seven different solvents (and in the gas phase), in which the dienes are butadiene, cyclopentadiene, cyclohexadiene, and cycloheptadiene; the dienophiles are the 1-, 1,1-, and 1,1,2-cyanoethylene derivatives; the solvents were chosen to sample a range of dielectric constants from heptane to ethanol. These components provide twenty-four symmetry-enthalpy DFT-calculated correlation lines (out of which only one case is a relatively mild exception) that show the general trend of increase in enthalpy as symmetry decreases. The various combinations between the dienophiles, cyanoethylenes, and solvents provide all kinds of sources for symmetry deviations; it is therefore remarkable that although the enthalpy of activation is dictated by various parameters, symmetry emerges as a primary parameter. In our analysis we also bisected this overall picture into solvent effects and geometry variation effects to evaluate under which conditions the electronic effects are more dominant than symmetry effects.

Chiral Ramachandran Plots I: Glycine

“…It should be noted that the nearest achiral structure is a mathematical construct which varies for each analyzed structure (for instance, for each Gly residue). Many correlations between the CSM or the CCM and chemical, physical, or biochemical properties that depend on symmetry or chirality have been successfully established; − alternative approaches have been proposed by, e.g., Jamroz et al…”

Effect of Temperature and Substitution on Cope Rearrangement: A Symmetry Perspective

“…Excellent correlations were found between the CSM and various physical and chemical properties . In particular, it has been shown that the variation of the CSM values along the IRC can serve as an indicator for the progress of a reaction. , …”

Density Functional Theory Calculations in Stereochemical Determination of Terpecurcumins J–W, Cytotoxic Terpene-Conjugated Curcuminoids from Curcuma longa L.

“…Likewise, NOE enhancements of H-4/H-15″, as well as H-2″/H-7″ and CH 3 -14″, indicated that H-4, H-2″, H-15″, and the side chain at C-6″ were on the other side. The trans -relationship between H-3 and H-4 complied with the Alder–Stein rule . From a biosynthetic point of view, compound 3 could be derived from curcumin and (−)-α-zingiberene via Diels–Alder [4 + 2] cycloaddition.…”

“…The transrelationship between H-3 and H-4 complied with the Alder− Stein rule. 16 From a biosynthetic point of view, compound 3 could be derived from curcumin and (−)-α-zingiberene via Diels−Alder [4 + 2] cycloaddition. (−)-α-Zingiberene is a major sesquiterpene in turmeric, and its absolute configuration had been assigned as 6″R,7″S by chemical synthesis.…”