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 (PS-PPh3), 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. Post-constructional peptide modification was also demonstrated, affording two N-beta-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.