Axial shielding of Pd(II) complexes enables perfect stereoretention in Suzuki-Miyaura cross-coupling of Csp 3 boronic acids

Jonathan W. Lehmann, Ian T. Crouch, Daniel J. Blair, Melanie Trobe, Pulin Wang, Junqi Li, Martin Burke

Research output: Contribution to journalArticle

Abstract

Stereocontrolled Csp 3 cross-coupling can fundamentally change the types of chemical structures that can be mined for molecular functions. Although considerable progress in achieving the targeted chemical reactivity has been made, controlling stereochemistry in Csp 3 cross-coupling remains challenging. Here we report that ligand-based axial shielding of Pd(II) complexes enables Suzuki-Miyaura cross-coupling of unactivated Csp 3 boronic acids with perfect stereoretention. This approach leverages key differences in spatial orientation between competing pathways for stereoretentive and stereoinvertive transmetalation of Csp 3 boronic acids to Pd(II). We show that axial shielding enables perfectly stereoretentive cross-coupling with a range of unactivated secondary Csp 3 boronic acids, as well as the stereocontrolled synthesis of xylarinic acid B and all of its Csp 3 stereoisomers. We expect these ligand design principles will broadly enable the continued search for practical and effective methods for stereospecific Csp 3 cross-coupling.

Original languageEnglish (US)
Article number1263
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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Boronic Acids
cross coupling
Shielding
shielding
acids
Ligands
Chemical reactivity
Stereochemistry
Stereoisomerism
ligands
stereochemistry
reactivity
synthesis

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Axial shielding of Pd(II) complexes enables perfect stereoretention in Suzuki-Miyaura cross-coupling of Csp 3 boronic acids . / Lehmann, Jonathan W.; Crouch, Ian T.; Blair, Daniel J.; Trobe, Melanie; Wang, Pulin; Li, Junqi; Burke, Martin.

In: Nature communications, Vol. 10, No. 1, 1263, 01.12.2019.

Research output: Contribution to journalArticle

Lehmann, Jonathan W. ; Crouch, Ian T. ; Blair, Daniel J. ; Trobe, Melanie ; Wang, Pulin ; Li, Junqi ; Burke, Martin. / Axial shielding of Pd(II) complexes enables perfect stereoretention in Suzuki-Miyaura cross-coupling of Csp 3 boronic acids In: Nature communications. 2019 ; Vol. 10, No. 1.
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