Catalyst shuttling enabled by thermoresponsive polymeric ligand: facilitating efficient cross-couplings with continuously recyclable ppm levels of palladium

A polymeric monophosphine ligand WePhos has been synthesized and complexed with Pd(OAc)2 to generate a thermoresponsive pre-catalyst that can shuttle between water and organic phases as regulated by temperature. The structure of polymeric ligand was confirmed with MALDI-TOF mass spectrometry, SEC analysis, as well as NMR measurements. This polymeric metal complex enables highly efficient Pd-catalyzed cross-couplings and tandem reactions using 50 to 500 ppm palladium, and facilitates reactions that are tolerant to a broad spectrum of (hetero)aryl substrates and functional groups as demonstrated with 73 examples in up to 99% isolated yields. Notably, 97% Pd was remained in the aqueous phase after 10 runs of catalyst recycling experiments as determined by ICP-AES measurement, indicating the highly efficient catalyst transfer. Furthermore, a continuous-catalyst-recycling approach has been successfully developed based on flow chemistry in combination with the catalyst shuttling behavior, allowing Suzuki-Miyaura couplings to be conducted at gram-scales with down to 10 ppm Pd loading. Given the significance of transition-metal-catalyzed cross-coupling and increasing interests in sustainable chemistry, this work takes an important step towards the development of responsive catalyst in addition to high activity by tuning the structures of ligands in combination with polymer science.