A Self-Assembling NHC-Pd-Loaded Calixarene as a Potent Catalyst for the Suzuki-Miyaura Cross-Coupling Reaction in Water.

Arnaud Peramo,Vincent Huc,Julie Mougin,Ibrahim Abdellah,Didier Desmaële,Patrick Couvreur,Cyril Martini,Shannon Pecnard

doi:10.3390/molecules25061459

Abstract

Nanoformulated calix[8]arenes functionalized with N-heterocyclic carbene (NHC)-palladium complexes were found to be efficient nano-reactors for Suzuki-Miyaura cross-coupling reactions of water soluble iodo- and bromoaryl compounds with cyclic triol arylborates at low temperature in water without any organic co-solvent. Combined with an improved one-step synthesis of triol arylborates from boronic acid, this remarkably efficient new tool provided a variety of 4′-arylated phenylalanines and tyrosines in good yields at low catalyst loading with a wide functional group tolerance.

Highlights

The water and functional group tolerance of the Suzuki-Miyaura reaction culminated in the cross-coupling of iodoarylated proteins under physiological conditions opening the way to a realm of chemical-biology applications [17,18,19,20]
Chlorobutyl appendages were first bound to the eight free phenol groups of benzyloxycalix[8]arene and the chlorides displaced with 3-(mesityl)-2,3-dihydro-1H-imidazole
N-heterocyclic carbene (NHC)-palladium complexes gave highly stable nanosuspension endowed with high catalytic activity for the Suzuki–Miyaura couplings in pure water

Summary

Introduction

The Suzuki-Miyaura reaction has emerged as one of the most powerful tool for C–C bond formation because of its compatibility with a broad range of functional groups giving rise to numerous applications throughout organic chemistry, synthesis of pharmaceutical compounds [1,2,3] and materials science [4,5].Aqueous Suzuki-Miyaura cross-coupling reactions are promising due to the water tolerance of boronic acids compared with the organometallic reagents required for other cross-coupling protocols.As a consequence, the Suzuki-Miyaura reaction has been widely developed under homogenous or heterogenous catalytic conditions in water media and a large array of different ligands and palladium complexes including micellar catalysis conditions nanoparticulate formulations have been designed to increase efficiency under aqueous conditions [6,7,8,9,10,11,12,13,14,15,16]. Reactions in water are not restricted to those with biomolecules: due to water’s ideal proprieties (abundance, environmental compatibility, non-toxicity and nonflammability) a wide range of catalytic and organic reactions have been developed in water as solvent [21]. In this context, calixarene macromolecules have been used for Suzuki-Miyaura cross-coupling reactions as supports for palladium catalyst. There are a few examples of the use of calix[4]arenes as Molecules 2020, 25, 1459; doi:10.3390/molecules25061459 www.mdpi.com/journal/molecules

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Conclusion