Mechanistic Pathways in Cyanide-Mediated Benzoin Condensation: A Comprehensive Electron Localisation Function (ELF) and Catastrophe Theory Analysis of the Umpolung Reaction

Overview

Journal Molecules

Publisher MDPI

Date 2025 Jan 25

PMID 39860246

Authors

Michal Michalski

Slawomir Berski

Affiliations

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Abstract

This research investigates the mechanism of the cyanide-type umpolung reaction in benzoin condensation using topological analysis of ELF and catastrophe theory. The study achieves a comprehensive understanding of the evolution of chemical bonds and non-bonding electron density in the reaction of benzaldehyde and cyanide ions. The results reveal that the reaction proceeds through five transition state structures, with the formation of Lapworth's cyanohydrin being the rate-determining step. The study characterises topological catastrophes in the evolution of the ELF field and provides a detailed description of the evolution of electron density in the mechanism of the reaction. An in-depth analysis of ELF catastrophes confirms the well-established Lapworth mechanism.

References

Bursch M, Mewes J, Hansen A, Grimme S . Best-Practice DFT Protocols for Basic Molecular Computational Chemistry. Angew Chem Int Ed Engl. 2022; 61(42):e202205735. PMC: 9826355. DOI: 10.1002/anie.202205735. View

Polo V, Andres J, Berski S, Domingo L, Silvi B . Understanding reaction mechanisms in organic chemistry from catastrophe theory applied to the electron localization function topology. J Phys Chem A. 2008; 112(31):7128-36. DOI: 10.1021/jp801429m. View

Juhl M, Lee J . Umpolung Reactivity of Aldehydes toward Carbon Dioxide. Angew Chem Int Ed Engl. 2018; 57(38):12318-12322. DOI: 10.1002/anie.201806569. View

Wang S, Cheng B, Srsen M, Konig B . Umpolung Difunctionalization of Carbonyls via Visible-Light Photoredox Catalytic Radical-Carbanion Relay. J Am Chem Soc. 2020; 142(16):7524-7531. PMC: 7252948. DOI: 10.1021/jacs.0c00629. View

Lee , Yang , PARR . Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B Condens Matter. 1988; 37(2):785-789. DOI: 10.1103/physrevb.37.785. View

He Y, Xue Y . Mechanism insight into the cyanide-catalyzed benzoin condensation: a density functional theory study. J Phys Chem A. 2010; 114(34):9222-30. DOI: 10.1021/jp103031q. View

Polo V, Andres J, Castillo R, Berski S, Silvi B . Understanding the molecular mechanism of the 1,3-dipolar cycloaddition between fulminic acid and acetylene in terms of the electron localization function and catastrophe theory. Chemistry. 2004; 10(20):5165-72. DOI: 10.1002/chem.200400161. View

Bai D, Guo X, Wang X, Xu W, Cheng R, Wei D . Umpolung reactivity of strained C-C σ-bonds without transition-metal catalysis. Nat Commun. 2024; 15(1):2833. PMC: 10987681. DOI: 10.1038/s41467-024-47169-9. View

Lu T, Chen F . Multiwfn: a multifunctional wavefunction analyzer. J Comput Chem. 2011; 33(5):580-92. DOI: 10.1002/jcc.22885. View

10.

Chen Y, Duan M, Lin S, Liu Y, Cheng J, Xiang S . Organocatalytic aromatization-promoted umpolung reaction of imines. Nat Chem. 2023; 16(3):408-416. DOI: 10.1038/s41557-023-01384-x. View

11.

Shukla P, Mishra P, Baruah T, Zope R, Jackson K, Johnson J . How Do Self-Interaction Errors Associated with Stretched Bonds Affect Barrier Height Predictions?. J Phys Chem A. 2023; 127(7):1750-1759. PMC: 10032567. DOI: 10.1021/acs.jpca.2c07894. View

12.

Bugaut X, Glorius F . Organocatalytic umpolung: N-heterocyclic carbenes and beyond. Chem Soc Rev. 2012; 41(9):3511-22. DOI: 10.1039/c2cs15333e. View

13.

Andres J, Berski S, Silvi B . Curly arrows meet electron density transfers in chemical reaction mechanisms: from electron localization function (ELF) analysis to valence-shell electron-pair repulsion (VSEPR) inspired interpretation. Chem Commun (Camb). 2016; 52(53):8183-95. DOI: 10.1039/c5cc09816e. View

14.

Bruno I, Cole J, Edgington P, Kessler M, Macrae C, McCabe P . New software for searching the Cambridge Structural Database and visualizing crystal structures. Acta Crystallogr B. 2002; 58(Pt 3 Pt 1):389-97. DOI: 10.1107/s0108768102003324. View

15.

Berski S, Andres J, Silvi B, Domingo L . New findings on the Diels-Alder reactions. An analysis based on the bonding evolution theory. J Phys Chem A. 2006; 110(51):13939-47. DOI: 10.1021/jp068071t. View