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Parameterization of phosphine ligands reveals mechanistic pathways and predicts reaction outcomes

Abstract

The mechanistic foundation behind the identity of a phosphine ligand that best promotes a desired reaction outcome is often non-intuitive, and thus has been addressed in numerous experimental and theoretical studies. In this work, multivariate correlations of reaction outcomes using 38 different phosphine ligands were combined with classic potentiometric analyses to study a Suzuki reaction, for which the site selectivity of oxidative addition is highly dependent on the nature of the phosphine. These studies shed light on the generality of hypotheses regarding the structural influence of different classes of phosphine ligands on the reaction mechanism(s), and deliver a methodology that should prove useful in future studies of phosphine ligands.

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Figure 1: Strategy for parameterizing monodentate phosphine ligands.
Figure 2: General steps used for deriving a suitable model.
Figure 3: Models identified with optimal predictive ability.
Figure 4: Mechanistic hypothesis and studies of ligand concentration effects.
Figure 5: Models of predicted versus measured ΔΔG values for subsets of the phosphines using parameters from the maximum and minimum cone-angle conformers.

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Acknowledgements

This work was supported by the National Science Foundation (CHE-1361296). The support and resources from the Center for High Performance Computing at the University of Utah are gratefully acknowledged.

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Z.L.N., A.M. and M.S.S. conceived and designed the experiments; Z.L.N. performed the experiments; D.P.H. helped perform and analyse the electrochemical experiments; Z.L.N., A.M., D.P.H. and M.S.S. analysed the data; Z.L.N., A.M., D.P.H. and M.S.S. co-wrote the paper.

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Correspondence to Matthew S. Sigman.

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The authors declare no competing financial interests.

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Niemeyer, Z., Milo, A., Hickey, D. et al. Parameterization of phosphine ligands reveals mechanistic pathways and predicts reaction outcomes. Nature Chem 8, 610–617 (2016). https://doi.org/10.1038/nchem.2501

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