Direct SN2 or SN2X Manifold – Mechanistic Study of Ion-Pair Catalyzed Carbon(sp3)-Carbon(sp3) Bond Formation

15 November 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Density functional theory (DFT) is used in this work to predict the mechanism for constructing congested quaternary-quaternary carbon(sp3)–carbon(sp3) bonds in a pentanidium catalyzed substitution reaction. Computational mechanistic studies were carried out to investigate the proposed SN2X manifold, which consists of two primary elementary steps: halogen atom transfer (XAT) and subsequent SN2. For the first calculated model on original experimental substrates, XAT reaction barriers were more kinetically competitive than an SN2 pathway and connects to thermodynamically stable intermediates. Extensive computational screening-modelling were then done on various substrate combinations designed to study steric influence and to understand the mechanistic rationale, and calculations reveal that sterically congested substrates prefer the SN2X manifold over SN2. Different halides as leaving groups were also screened and it was found that the reactivity increases in order of Br > Cl > F in agreement of the strength of C–X bonds. However, DFT modelling suggests that chlorides can be a viable substrate for the SN2X process which should be further explored experimentally. Finally, ONIOM calculations on the full catalyst model were carried out to rationalize the stereoselectivity which corroborates with experimental results.


Computational modelling
Ion-pair catalysis
Halogenophillic substitution (SN2X)
C-C bond
Reaction mechanism

Supplementary materials

Electronic supporting information
Electronic supporting information for DFT model summary, table of energies and gaussian archive files.


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