Relationships between Product Ratios in Ambimodal Pericyclic Reactions and Bond Lengths in Transition Structures

Abstract

Ambimodal reactions involve a single transition state leading to multiple products. In such reactions, transition state theory gives no information about the ratio of products that are formed, and molecular dynamics must be performed to predict this ratio. Understanding the relationship between the transition structure and the product ratio is a long-standing problem in molecular dynamics. We have studied 15 ambimodal pericyclic reactions and investigated the relationship between the TS bond lengths in the saddle points and the product ratios from trajectory simulations. A linear correlation, ln(B:A) = -9.4(Bond 3 - Bond 2), is found with R = 0.92, where A and B refer to the products formed upon formation of bonds 2 and 3, respectively. The correlation shows that the ratio of products formed after the bifurcation is related to the partial bond lengths, and corresponding bond orders, in the transition state.

Enzyme-catalysed [6+4] cycloadditions in the biosynthesis of natural products

“…7a). The preference for [6+4] adduct 6 is consistent with the shorter partial C-C bond (2.70 Å) in TS-1 compared to the longer partial C-C bond (2.86 Å) that leads to [4+2] adduct 7 24 (Fig. 2a).…”

Designing Reactions with Post-Transition-State Bifurcations: Asynchronous Nitrene Insertions into C–C σ Bonds

“…Houk and co-workers have recently described geometric parameters of ambimodal TSSs that are predictive of product distributions for cycloadditions involving PTSBs. 32 Third, examination of models of valley-ridge inflection (VRI) points (see Supplemental Information Section S5 for details on locating them) indicates that the more a VRI point resembles TSS2 (in terms of interatomic distances and angles; see Supplemental Information Section S4 for data), the more balanced a product distribution is observed, i.e., the more [3.2.2] product is formed. Noncovalent interaction (NCI) analysis 33,34 also shows that VRI points for reactions with more balanced product distributions have additional stabilizing intramolecular interactions (e.g., apparent attractive interactions between F and N atoms); an example is shown in Figure 6 (see Supplemental Information Sections S6 and S7 for other structures).…”

The expanding world of biosynthetic pericyclases: cooperation of experiment and theory for discovery

“…For example, intramolecular ambimodal pericyclic reactions would occur in substrates bearing two dienolic components as seen in LepI-catalyzed reactions, which can undergo formal Diels-Alder or inverse electron demand Diels-Alder reactions. 86 Intermediates in natural product biosynthetic pathways that have this structural hallmark are likely to contain pericyclases that can catalyze ambimodal pericyclic reactions.…”