Organometallic Chemistry

A reactivity map for oxidative addition enables quantitative predictions for multiple catalytic reaction classes

Authors

Abstract

Making accurate, quantitative predictions of chemical reactivity based on molecular structure is an unsolved problem in chemical synthesis, particularly for complex molecules. We report a generally applicable, mechanistically based structure-reactivity approach to create a quantitative model for the oxidative addition of (hetero)aryl electrophiles to palladium(0), which is a key step in myriad catalytic processes. This model links simple molecular descriptors to relative rates of oxidative addition for 79 substrates, including chloride, bromide and triflate leaving groups. Because oxidative addition often controls the rate and/or selectivity of palladium-catalyzed reactions, this model can be used to make quantitative predictions about catalytic reaction outcomes. Demonstrated applications include a multivariate linear model for the initial rate of Sonogashira coupling reactions, and successful site-selectivity predictions for a series of multihalogenated substrates relevant to the synthesis of pharmaceuticals and natural products.

Version notes

Incorporation of aryl triflates into a unified model; expanded discussion of models and mechanistic aspects; additional details in application case studies.

Content

Thumbnail image of Lu-Donnecke-Paci-Leitch-Pd-Reactivity-Map-v2.pdf

Supplementary material

Thumbnail image of Lu-Donnecke-Paci-Leitch-Pd-Reactivity-Map-SI-v2.pdf
A reactivity map for oxidative addition enables quantitative predictions for multiple catalytic reaction classes (supporting information)
Supporting information including materials, experimental and computational methods, data, and additional description of analyses and/or experiments that are referred to in the main text.
Thumbnail image of Lu-Donnecke-Paci-Leitch-Pd-Reactivity-Map-Data-Tables-v2.xlsx
A reactivity map for oxidative addition enables quantitative predictions for multiple catalytic reaction classes (data tables)
Expanded data tables containing all information used to build regression models, including experimental data and molecular descriptors.
Thumbnail image of Lu-Donnecke-Paci-Leitch-Pd-Reactivity-Map-xyz-Files.zip
A reactivity map for oxidative addition enables quantitative predictions for multiple catalytic reaction classes (xyz files)
Zip folder containing all xyz coordinate files for calculated structures, including: 79 oxidative addition substrates; 11 Pd pi-complex intermediates; 6 oxidative addition transition states and the corresponding cis and trans products; 29 Sonogashira substrates; 17 phosphine ligands and their corresponding PdL and PdL2 complexes; and 33 site-selectivity substrates.