Dynamic Effects on Migratory Aptitudes in Carbocation Reactions

Abstract

Carbocation rearrangement reactions are of great significance to synthetic and biosynthetic chemistry. In pursuit of a scale of inherent migratory aptitude that takes into account dynamic effects, both uphill and downhill ab initio molecular dynamics (AIMD) simulations were used to examine competing migration events in a model system designed to remove steric and electronic biases. The results of these simulations were combined with detailed investigations of potential energy surface topography and variational transition state theory calculations to reveal the importance of nonstatistical dynamic effects on migratory aptitude.

C–H Insertion in Dirhodium Tetracarboxylate-Catalyzed Reactions despite Dynamical Tendencies toward Fragmentation: Implications for Reaction Efficiency and Catalyst Design

“…We previously proposed that a post-transition state bifurcation (PTSB) is involved in β-lactone formation promoted by dirhodium tetracarboxylates (Scheme ). Reactions with PTSBs involve a single ″ambimodal″ transition structure (TS) that leads directly to two products via pathways that monotonically decrease in potential energy (e.g., TS1 in Figure ), i.e., no potential energy surface (PES) minima separate the ambimodal TS from either product. − In this circumstance, traditional transition state theory cannot predict the product distribution, since both products share a transition state (dividing surface), and product selectivity must result from a nonstatistical dynamic effect. − Consequently, molecular dynamics (MD) simulations initiated from the ambimodal TS are typically used to reveal kinetic preferences for the formation of one product over the other, which results from the momentum possessed by reacting molecules as they pass through the transition state/dividing surface. , We argued that the PTSB for the reaction shown in Scheme allows leakage to side products, thereby reducing the yields of the desired β-lactones (Figure ). Consistent with this model, experimental evidence for the fragmentation products we predict would arise via the PTSB was reported. , This example shows how failing to detect a PTSB can preclude the rational reduction of unwanted side products.…”

Portable Models for Entropy Effects on Kinetic Selectivity

“…This sort of inter-transition state communication is not accounted for in standard models. While it has been proposed for reactions such as the competing water loss/1,2-alkyl shift processes shown in Figure b, it is not yet clear how common such a scenario is. That being said, this scenario is related to a much-studied class of reactions involving flat regions of PESs with multiple exit channels rather than simple transition states separating reactants from products–so-called “calderas,” “mesas,” “para-intermediates,” or “twixtyls” .…”

“…(a) PES (as a 2D contour map with energy coded by color) for a reaction with an inter-transition state roaming region. Adapted from ref . Copyright 2021 American Chemical Society.…”

Role of Noncovalent Interactions in Inducing High Enantioselectivity in an Alcohol Reductive Deoxygenation Reaction Involving a Planar Carbocationic Intermediate

“…While there have been a number of efforts in engaging easily accessible racemic starting materials to make enantiomerically enriched products, the one which is particularly valuable is dynamic kinetic asymmetric transformation (DYKAT). , Of direct significance to the present work is an overarching connection between one of the earliest known reactive intermediates, namely carbocations, and the newer strategies in asymmetric catalysis discussed above . In the traditional practice of asymmetric catalysis, the participation of planar carbocations is generally considered undesirable due to potential racemization over the course of the reaction in the absence of a suitable chiral catalyst or promoter.…”