Fully aqueous and air-compatible cross-coupling of primary alkyl halides with aryl boronic species : a possible and facile method
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.
Citation
Molyneux , S & Goss , R 2023 , ' Fully aqueous and air-compatible cross-coupling of primary alkyl halides with aryl boronic species : a possible and facile method ' , ACS Catalysis , vol. 13 , no. 9 , pp. 6365-6374 . https://doi.org/10.1021/acscatal.3c00252
Publication
ACS Catalysis
Status
Peer reviewed
ISSN
2155-5435Type
Journal article
Description
Funding: The authors thank the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT) for financial support [Ph.D. studentship to S.M.; Grant code: EP/L016419/1].Collections
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