A comparison of immobilised triphenylphosphine and 1-hydroxybenzotriazole as mediators of catch-and-release acylation under flow conditions

Described herein is a comparative study of immobilised triphenylphosphine (PS-PPh3) and 1-hydroxybenzotriazole (PS-HOBt) to mediate amide couplings under continuous flow. Compared to Appel-type amidations (PSPPh3), the developed 'catch-and-release' approach (PS-HOBt) afforded near-quantitative amide conversions. Utilising this strategy, sulfonyl chloride amenability enabled facile access to an expanded library of sulfonate and sulfonamides. Postconstructional peptide modification was also demonstrated, affording two Nβ -functionalised pentapeptides in high yields and purities. In contrast to frequently utilised coupling agents, the PS-HOBt resin could be recycled six times without a reduction in efficacy or regeneration requirements.