Fully aqueous and air-compatible cross-coupling of primary alkyl halides with aryl boronic species: a possible and facile method

Samuel Molyneux, Rebecca Goss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Downloads (Pure)

Abstract

Aqueous transformations confer many advantages, including decreased environmental impact and increased opportunity for biomolecule modulation. Although several studies have been conducted to enable the cross-coupling of aryl halides in aqueous conditions, until now a process for the cross-coupling of primary alkyl halides in aqueous conditions was missing from the catalytic toolbox and considered impossible. Alkyl halide coupling in water suffers from severe problems. The reasons for this include the strong propensity for β-hydride elimination, the need for highly air- and water-sensitive catalysts and reagents, and the intolerance of many hydrophilic groups to cross-coupling conditions. Here, we report a broadly applicable and readily accessible process for the cross-coupling of water-soluble alkyl halides in water and air by using simple and commercially available bench-stable reagents. The trisulfonated aryl phosphine TXPTS in combination with a water-soluble palladium salt Na2PdCl4 allowed for the Suzuki−Miyaura coupling of water-soluble alkyl halides with aryl boronic acids, boronic esters, and borofluorate salts in mild, fully aqueous conditions. Multiple challenging functionalities, including unprotected amino acids, an unnatural halogenated amino acid within a peptide, and herbicides can be diversified in water. Structurally complex natural products were used as testbeds to showcase the late-stage tagging methodology of marine natural products to enable liquid chromatography−mass spectrometry (LC−MS) detection. This enabling methodology therefore provides a general method for the environmentally friendly and biocompatible derivatization of sp3 alkyl halide bonds.
Original languageEnglish
Pages (from-to)6365-6374
Number of pages10
JournalACS Catalysis
Volume13
Issue number9
Early online date24 Apr 2023
DOIs
Publication statusPublished - 5 May 2023

Keywords

  • Aqueous
  • Cross-coupling
  • Sustainable
  • Biocompatible
  • Late-stage diversification

Fingerprint

Dive into the research topics of 'Fully aqueous and air-compatible cross-coupling of primary alkyl halides with aryl boronic species: a possible and facile method'. Together they form a unique fingerprint.

Cite this