Between a reactant rock and a solvent hard place – molecular corrals guide aromatic substitutions

Abstract

A novel reaction mechanism is presented for an ortho-magnesium carboxylate driven aromatic nucleophilic substitution in naphthoic acids, supported by high-level density functional theory. Results show that the rate-determining aspects involve an R-group transfer from a Grignard reagent Mg-atom to the C1-atom on a naphthalene ring. This transfer is moderated by a molecular corral comprised of two solvent THF molecules and the naphthoic acid, which collectively marshal the R-group into position. The CAM-B3LYP method was employed together with the all-electron DZVP basis set. Solvent was treated using an implicit dielectric continuum (PCM method) and IDSCRF atomic-radii. Further evolved solvent models were also investigated, consisting of explicit solvating particles forming a primary solvation layer framing the reaction center. Reaction barriers obtained are in close agreement with experimental trends, with R-group substituent-identity tempering repulsion with the molecular corral, in-turn modulating the free-energy barriers. Partitioning of the dynamic bases of entropy contribution to free-energy was central to the successful experimental-theoretical synergy.

Semicontinuum (Cluster-Continuum) Modeling of Acid-Catalyzed Aqueous Reactions: Alkene Hydration

“…Henchman points out that the ambiguity can be linked to an arbitrary choice of reference frame: he states that use of the molecule frame (MF) puts no restriction on the solute but requires cavitation of the solvent, while use of the system frame (SF) forces consideration of local hindrance of all molecules and should not require a cavitation term . We also mention in passing that we, like De-Cai Fang, − have in the past switched from cavitation to the damping of solute entropy (a system frame idea) to improve default free-energy predictions in organic solvents.…”

A Theoretical Probe of Mechanistic Trichotomy in RhIII‐Catalyzed Annulation with Alkyne MIDA Boronates: Roles of Salt, Solvent, and Coupling Partner

“…Our method is based on the free volume, which is free for a solute molecule moving along three axes within the cavity that is constituted by solute and solvent molecules, and this program has been successfully applied to different reaction systems. [30] In addition, the dispersion-corrected DFT-D [31] was used to characterize the stationary points along the reaction pathways, which was denoted as B3LYP-IDSCRF-D3.…”

A Theoretical Study of Ene Reactions in Solution: A Solution‐Phase Translational Entropy Model

“…Free energies have been reported from standard determinations emerging from the G09 output, in addition to estimation using solution-phase translational entropy,w hich has been coded into our THERMO program. [36] This method has been applied into different systems, [10,37] and it has proven to be quite encouraging. The contribution of low-lying modes (in general less than 100 cm À1 )t ot he entropy is replaced by ac orresponding rotational entropy (quasi-RRHO approach), [38] and for long chain molecules, the conformational entropies are also considered (see Figure S2 in the Supporting Information).…”