Towards a Unified Fold-Cusp Model for Bond Polarity Scaling: Electron Rearrangements in the Pyrolytic Isomerization of Cubane to Cyclooctatetraene DOI Creative Commons
Leandro Ayarde‐Henríquez, Cristian Guerra,

Patricia Pérez

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Abstract Context This study meticulously examines the criteria for assigning electron rearrangements along intrinsic reaction coordinate (IRC) leading to bond formation and breaking processes during pyrolytic isomerization of cubane (CUB) 1,3,5,7-cyclooctatetraene (COT) from both thermochemical bonding perspectives. Notably, no cusp-type function was detected in initial thermal conversion step CUB bicyclo[4.2.0]octa-2,4,7-triene (BOT). Contrary previous reports, all relevant fluxes pairing density must be described terms fold unfolding. The transannular ring opening second highlights characteristics indicative a catastrophe, facilitating direct comparison with features. fact underscores critical role symmetry persistence near topographical events determining type bifurcation. A fold-cusp unified model scaling polarity chemical bonds is proposed, integrating ubiquitous classes such as isomerization, bimolecular nucleophilic substitution, cycloaddition. analysis reveals that index (BPI) values within [0, 10− 5]au interval correlate cusp unfolding, whereas spans over broader [10− 3, ∞) au spectrum. These insights emphasize polynomial suitable describing involving symmetric distributions, particularly those homolytic cleavages; contrast, characterizes most events. Methods Geometry optimization frequency calculations were conducted using various DFT functionals. In line recent findings concerning rigorous application BET, characterization formations scissions via unfoldings carried out by carefully monitoring determinant Hessian matrix at potentially degenerate CPs their relative distance. computed gas-phase activation enthalpies strongly align experimental values, stressing adequacy chosen levels theory ELF topography IRC. BPI determined methodology proposed Allen collaborators.

Language: Английский

Towards a unified fold-cusp model for bond polarity scaling: electron rearrangements in the pyrolytic isomerization of cubane to cyclooctatetraene DOI
Leandro Ayarde‐Henríquez, Cristian Guerra, Patricia Pérez

et al.

Journal of Molecular Modeling, Journal Year: 2025, Volume and Issue: 31(2)

Published: Jan. 13, 2025

Language: Английский

Citations

0
3-Oxabicyclo[3.1.1]heptanes as Isosteres of meta-Substituted Benzene Rings DOI
Jennifer Morvan, Evelien Renders, Peter Buijnsters

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Replacement of the aromatic rings in drug candidates with isosteric rigid sp3-rich scaffolds can improve physicochemical properties, increase chance progressing molecule development, and open new chemical space. Isosteres meta-substituted benzenes remain challenging due to difficulty mimicking exit vector angles bond distances. Herein, we report synthesis 1,5-disubstituted 3-oxabicyclo[3.1.1]heptanes (oxa-BCHeps), which serve as saturated isosteres phenyl a similar geometric arrangement. This structural motif be obtained under mild reaction conditions via acid-mediated isomerization (2-oxaspiro[3.3]heptan-6-yl)methanols using catalytic quantities pyridinium chloride (PyrHCl). We demonstrate utility this methodology by preparing various building blocks for use medicinal chemistry incorporating 3-oxa-BCHep into anticancer sonidegib, improving its such permeability, metabolic stability, solubility.

Language: Английский

Citations

0
Late-Stage N-Atom Deletion of Multisubstituted 2-Azabicyclo[2.1.1]Hexanes DOI

Ken Lin,

Qi Sun,

Pengcheng Tang

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 5825 - 5834

Published: March 25, 2025

Rigid three-dimensional scaffolds such as 2-azabicyclo[2.1.1]hexanes (aza-BCHs) and bicyclo[1.1.1]pentanes (BCPs) serve unique saturated isosteres of arenes, offering distinct substitution patterns due to their differing molecular exit vectors. This study introduces a skeletal editing strategy that efficiently transforms multisubstituted aza-BCHs into BCPs via an O-diphenylphosphinylhydroxylamine-promoted N-atom deletion process. method effectively addresses the challenge creating sterically hindered (2°)C–C(3°) bonds by removing nitrogen atom encased within bulky alkyl groups, reconstructing strained aza-BCH structure more BCP without generating undesired ring-opening diene byproducts. The used can be prepared from modified intermolecular [3 + 2] cycloaddition between bicyclo[1.1.0]butanes imines, making this practical. approach achieves remarkable efficiency, with yields up 99% scalability decagram quantities. resulting carboxylates further functionalized through decarboxylation, highlighting potential for programmed divergent synthesis BCPs. broad substrate scope high functional group tolerance protocol emphasize its versatility, it particularly valuable late-stage contained peptides, natural products, pharmaceuticals.

Language: Английский

Citations

0
Towards a Unified Fold-Cusp Model for Bond Polarity Scaling: Electron Rearrangements in the Pyrolytic Isomerization of Cubane to Cyclooctatetraene DOI Creative Commons
Leandro Ayarde‐Henríquez, Cristian Guerra, Eduardo Chamorro

et al.

Published: Aug. 16, 2024

This study meticulously examines the criteria for assigning electron rearrangements along intrinsic reaction coordinate (IRC) leading to bond formation and breaking processes during pyrolytic isomerization of cubane (CUB) 1,3,5,7 cyclooctatetraene (COT) from both thermochemical bonding perspectives. The computed gas phase activation enthalpies obtained using state-of-the-art DFT functionals strongly align with experimental values. Notably, no cusp-type function was detected in initial thermal conversion step CUB bicyclo[4.2.0]octa 2,4,7 triene ( as evidenced by examining modulus Hessian determinant at all potentially degenerate critical points (CPs) their relative distances. Contrary previous reports, relevant fluxes pairing density must be described terms fold unfolding. transannular ring opening second highlights characteristics indicative a catastrophe, facilitating direct comparison features. fact underscores role symmetry persistence near topographical events determining type bifurcation. A cusp unified model scaling polarity chemical bonds is proposed, integrating ubiquitous classes such isomerization, bimolecular nucleophilic substitution, cycloaddition. analysis reveals that index (BPI) values within [0, 10-5] au interval correlate unfolding, whereas spans over broader [10-3, ∞) spectrum. These insights emphasize polynomial suitable describing involving symmetric distributions, particularly those homolytic cleavages; contrast, characterizes most elucidated accurately captures COT stepwise mechanism, illustrated sequence catastrophes ELF topology changes IRC. rigorous application BET identifying unfoldings describe crucial are highlighted essential understanding predicting reactivity.

Language: Английский

Citations

2
Cubane Pyrolysis: Scaling Bond Polarity with Universal Polynomials DOI Creative Commons
Leandro Ayarde‐Henríquez, Cristian Guerra, Eduardo Chamorro

et al.

Published: Aug. 16, 2024

This study meticulously examines the criteria for assigning electron rearrangements along intrinsic reaction coordinate (IRC) leading to bond formation and breaking processes during pyrolytic isomerization of cubane (CUB) 1,3,5,7 cyclooctatetraene (COT) from both thermochemical bonding perspectives. The computed gas phase activation enthalpies obtained using state-of-the-art DFT functionals strongly align with experimental values. Notably, no cusp-type function was detected in initial thermal conversion step CUB bicyclo[4.2.0]octa 2,4,7 triene ( as evidenced by examining modulus Hessian determinant at all potentially degenerate critical points (CPs) their relative distances. Contrary previous reports, relevant fluxes pairing density must be described terms fold unfolding. transannular ring opening second highlights characteristics indicative a catastrophe, facilitating direct comparison features. fact underscores role symmetry persistence near topographical events determining type bifurcation. A cusp unified model scaling polarity chemical bonds is proposed, integrating ubiquitous classes such isomerization, bimolecular nucleophilic substitution, cycloaddition. analysis reveals that index (BPI) values within [0, 10-5] au interval correlate unfolding, whereas spans over broader [10-3, ∞) spectrum. These insights emphasize polynomial suitable describing involving symmetric distributions, particularly those homolytic cleavages; contrast, characterizes most elucidated accurately captures COT stepwise mechanism, illustrated sequence catastrophes ELF topology changes IRC. rigorous application BET identifying unfoldings describe crucial are highlighted essential understanding predicting reactivity.

Language: Английский

Citations

1
Towards a Unified Fold-Cusp Model for Bond Polarity Scaling: Electron Rearrangements in the Pyrolytic Isomerization of Cubane to Cyclooctatetraene DOI Creative Commons
Leandro Ayarde‐Henríquez, Cristian Guerra,

Patricia Pérez

et al.

Published: Aug. 19, 2024

This study meticulously examines the criteria for assigning electron rearrangements along intrinsic reaction coordinate (IRC) leading to bond formation and breaking processes during pyrolytic isomerization of cubane (CUB) 1,3,5,7 cyclooctatetraene (COT) from both thermochemical bonding perspectives. The computed gas phase activation enthalpies obtained using state-of-the-art DFT functionals strongly align with experimental values. Notably, no cusp-type function was detected in initial thermal conversion step CUB bicyclo[4.2.0]octa 2,4,7 triene ( as evidenced by examining modulus Hessian determinant at all potentially degenerate critical points (CPs) their relative distances. Contrary previous reports, relevant fluxes pairing density must be described terms fold unfolding. transannular ring opening second highlights characteristics indicative a catastrophe, facilitating direct comparison features. fact underscores role symmetry persistence near topographical events determining type bifurcation. A cusp unified model scaling polarity chemical bonds is proposed, integrating ubiquitous classes such isomerization, bimolecular nucleophilic substitution, cycloaddition. analysis reveals that index (BPI) values within [0, 10-5] au interval correlate unfolding, whereas spans over broader [10-3, ∞) spectrum. These insights emphasize polynomial suitable describing involving symmetric distributions, particularly those homolytic cleavages; contrast, characterizes most elucidated accurately captures COT stepwise mechanism, illustrated sequence catastrophes ELF topology changes IRC. rigorous application BET identifying unfoldings describe crucial are highlighted essential understanding predicting reactivity.

Language: Английский

Citations

1
Towards a Unified Fold-Cusp Model for Bond Polarity Scaling: Electron Rearrangements in the Pyrolytic Isomerization of Cubane to Cyclooctatetraene DOI Creative Commons
Leandro Ayarde‐Henríquez, Cristian Guerra,

Patricia Pérez

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Abstract Context This study meticulously examines the criteria for assigning electron rearrangements along intrinsic reaction coordinate (IRC) leading to bond formation and breaking processes during pyrolytic isomerization of cubane (CUB) 1,3,5,7-cyclooctatetraene (COT) from both thermochemical bonding perspectives. Notably, no cusp-type function was detected in initial thermal conversion step CUB bicyclo[4.2.0]octa-2,4,7-triene (BOT). Contrary previous reports, all relevant fluxes pairing density must be described terms fold unfolding. The transannular ring opening second highlights characteristics indicative a catastrophe, facilitating direct comparison with features. fact underscores critical role symmetry persistence near topographical events determining type bifurcation. A fold-cusp unified model scaling polarity chemical bonds is proposed, integrating ubiquitous classes such as isomerization, bimolecular nucleophilic substitution, cycloaddition. analysis reveals that index (BPI) values within [0, 10− 5]au interval correlate cusp unfolding, whereas spans over broader [10− 3, ∞) au spectrum. These insights emphasize polynomial suitable describing involving symmetric distributions, particularly those homolytic cleavages; contrast, characterizes most events. Methods Geometry optimization frequency calculations were conducted using various DFT functionals. In line recent findings concerning rigorous application BET, characterization formations scissions via unfoldings carried out by carefully monitoring determinant Hessian matrix at potentially degenerate CPs their relative distance. computed gas-phase activation enthalpies strongly align experimental values, stressing adequacy chosen levels theory ELF topography IRC. BPI determined methodology proposed Allen collaborators.

Language: Английский

Citations

0