Concerted or stepwise: how much do free-energy landscapes tell us about the mechanisms of elimination reactions?

Abstract

The base-catalyzed dehydration of benzene cis-1,2-dihydrodiols is driven by formation of an aromatic product as well as intermediates potentially stabilized by hyperaromaticity. Experiments exhibit surprising shifts in isotope effects, indicating an unusual mechanistic balance on the E2-E1cB continuum. In this study, both 1- and 2-dimensional free energy surfaces are generated for these compounds with various substituents, using density functional theory and a mixed implicit/explicit solvation model. The computational data help unravel hidden intermediates along the reaction coordinate and provide a novel conceptual framework for distinguishing between competing pathways in this and any other system with borderline reaction mechanisms.

Figure 1

Base-catalyzed dehydration of 3-substituted benzene cis-1,2-dihydrodiols. This process can occur either through a stepwise mechanism involving a carbanion intermediate (A) or, alternately, through a concerted E2 pathway (B) in which proton abstraction and bond cleavage to the leaving group occur in a single transition state.

Figure 2

Benzene cis-1,2-dihydrodiols examined in this work.

Figure 3

Free energy landscapes for the dehydration of (A) benzene cis-1,2-dihydrodiol and (B) the 3-cyano-substituted analogue, as a function of C–O distance to the leaving group (x-axis) and O–H distance to the base (y-axis). RS and IS denote reactant and intermediate states, respectively, and the approximate position of the transition state is marked by ‡. The product state can start to be seen at the upper right corner of the surface; however, extending the plot beyond 1.8 Å on the x-axis is complicated by the (expected) competing proton transfer from the OH groups of the benzene diol to the basic hydroxide ion.

Figure 4

Key stationary points for the dehydration of benzene cis-1,2,dihydrodiol. Shown here are the reactant complex (RS), the transition state for proton abstraction (TS₁), the carbanion intermediate (IS), the transition state for leaving group expulsion (TS₂), and the product complex (PS), obtained in a pure implicit solvent model.

Figure 5

Calculated free energy profiles for the hydrolysis of the 3-substituted benzene cis-1,2-dihydrodiols examined in this work. These profiles were obtained using an implicit solvent model with no extra explicit water molecules. All energies are in kcal/mol, relative to the relevant reactant complex.

Figure 6

Key stationary points for the dehydration of benzene cis-1,2,dihydrodiol. Shown here are the reactant complex (RS), the transition state for proton abstraction (TS₁), the carbanion intermediate (IS), the transition state for leaving group expulsion (TS₂), and the product complex (PS), obtained in a mixed implicit/explicit solvent model, with microsolvation from four added water molecules.