Posters

Presenting Author

Roberto M. Escobar

Academic/Professional Position (Other)

Integrative Biological and Chemical Sciences, Earth, Environmental and Marine Sciences

Presentation Type

Poster

Discipline Track

Biomedical ENGR/Technology/Computation

Abstract Type

Research/Clinical

Abstract

Carbon–carbon (C–C) bond activation has gained increased attention as a direct method for the synthesis of pharmaceuticals. Due to the thermodynamic stability and kinetic inaccessibility of the C–C bonds, however, activation of C–C bonds by homogeneous transition-metal catalysts under mild homogeneous conditions is still a challenge. Most of the systems in which the activation occurs either have aromatization or relief of ring strain as the primary driving force. The activation of unstrained C–C bonds of phosphaalkynes does not have this advantage. This study employs Density Functional Theory (DFT) calculations to elucidate Pt(0)-mediated C–CP bond activation mechanisms in phosphaalkynes. Investigating the thermal reductive elimination pathway from the C–CP bond activation product, we present energetics of resulting metal complexes, potential reaction intermediates, and reaction pathways leading to product formation in polar solvent (tetrahydrofuran). Additionally, comparisons between mesityl and phenyl groups, Pt(0) and Ni(0), and ligand-substituent variations reveal nuanced influences on product stability and transition state energies. Parallels with C–CN bond activation in benzonitriles with the Ni(0) fragment provide additional context, advancing understanding not only of C–C bond activation but also offering insights into broader transition-metal-catalyzed reactions. This study, encapsulating the intricacies of C–C bond activation in phosphaalkynes and its implications, contributes to the evolving landscape of pharmaceutical synthesis and catalysis. For example, the application of Pt(0)-mediated C–CP bond activation in the pharmaceutical industry offers innovative routes for drug synthesis, potentially leading to production of novel therapeutic agents with enhanced biological activities.

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Mechanistic Investigation of C—C Bond Activation of Phosphaalkynes with Pt(0) Complexes

Carbon–carbon (C–C) bond activation has gained increased attention as a direct method for the synthesis of pharmaceuticals. Due to the thermodynamic stability and kinetic inaccessibility of the C–C bonds, however, activation of C–C bonds by homogeneous transition-metal catalysts under mild homogeneous conditions is still a challenge. Most of the systems in which the activation occurs either have aromatization or relief of ring strain as the primary driving force. The activation of unstrained C–C bonds of phosphaalkynes does not have this advantage. This study employs Density Functional Theory (DFT) calculations to elucidate Pt(0)-mediated C–CP bond activation mechanisms in phosphaalkynes. Investigating the thermal reductive elimination pathway from the C–CP bond activation product, we present energetics of resulting metal complexes, potential reaction intermediates, and reaction pathways leading to product formation in polar solvent (tetrahydrofuran). Additionally, comparisons between mesityl and phenyl groups, Pt(0) and Ni(0), and ligand-substituent variations reveal nuanced influences on product stability and transition state energies. Parallels with C–CN bond activation in benzonitriles with the Ni(0) fragment provide additional context, advancing understanding not only of C–C bond activation but also offering insights into broader transition-metal-catalyzed reactions. This study, encapsulating the intricacies of C–C bond activation in phosphaalkynes and its implications, contributes to the evolving landscape of pharmaceutical synthesis and catalysis. For example, the application of Pt(0)-mediated C–CP bond activation in the pharmaceutical industry offers innovative routes for drug synthesis, potentially leading to production of novel therapeutic agents with enhanced biological activities.

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