The Houk–List transition states for organocatalytic mechanisms revisited

Abstract

International audienceThe ten year old Houk–List model for rationalising the origin of stereoselectivity in the organocatalysed intermolecular aldol addition is revisited, using a variety of computational techniques that have been introduced or improved since the original study. Even for such a relatively small system, the role of dispersion interactions is shown to be crucial, along with the use of basis sets where the superposition errors are low. An NCI (non-covalent interactions) analysis of the transition states is able to identify the noncovalent interactions that influence the selectivity of the reaction, confirming the role of the electrostatic NCH d+ /O dÀ interactions. Simple visual inspection of the NCI surfaces is shown to be a useful tool for the design of alternative reactants. Alternative mechanisms, such as proton-relays involving a water molecule or the Hajos–Parrish alternative, are shown to be higher in energy and for which computed kinetic isotope effects are incompatible with experiment. The Amsterdam manifesto, which espouses the principle that scientific data should be citable, is followed here by using interactive data tables assembled via calls to the data DOI (digital-object-identifiers) for calculations held on a digital data repository and themselves assigned a DOI

Perspective: Found in translation: Quantum chemical tools for grasping non-covalent interactions

“…The relevance of NCI for studying large systems has been demonstrated on DNA, proteins, as well as nanotubes, 205,206 polymers, 207 and crystals under high pressure. 208 Moreover, this tool has also been used to explore reactivity, 114,184,209,210 dynamics, 191 and solvation 211 effects. Likewise, DORI has been used to explain the mechanisms of alkylperoxyl radical termination, 212 to investigate the conformational behavior of peptides in different media, 213,214 to design new materials, 215 and has also served as a component of new density functionals.…”

Evaluating common QTAIM and NCI interpretations of the electron density concentration through IQA interaction energies and 1D cross-sections of the electron and deformation density distributions

“…NCI identifies inter-and intramolecular interactions by finding regions of low electron density between atoms where the reduced density gradient (RDG) tends to zero [2]. These regions are then classified as either "stabilizing", when electron density is concentrated, or "destabilizing", when electron density is depleted [2][3][4]47,48]. NCI therefore supplements typical QTAIM analysis in three ways: (i) it identifies an interaction in 3D space, whereas QTAIM only shows bridges, (ii) it can detect electron density concentration, despite the absence of an AIL, and (iii) it can also identify interactions due to regions of electron depletion.…”

A benchmark for the non-covalent interaction (NCI) index or… is it really all in the geometry?

“…It was found that the stability of conformers was given not only by the electrostatics in the NCH δ+ · · ·O δ− interaction, but also by the T-shape dispersive interactions between the proline and the phenyk group, specially important in the syn conformers (see Ref. 27 for more details). In this revisit, several models 27 were devised to boost non-covalent interactions altering the diastereoselectivity ratio.…”