Continuous Flow Synthesis of [Au(NHC)(Aryl)] (NHC=N‐Heterocyclic Carbene) Complexes

Abstract

The use of weak and inexpensive bases has recently opened promising perspectives towards the simpler and more sustainable synthesis of Au(I)-aryl complexes with valuable applications in catalysis, medicinal chemistry, and materials science. In recent years, continuous manufacturing has shown to be a reliable partner in establishing sustainable and controlled process scalability. Herein, the first continuous flow synthesis of a range of Au(I)-aryl starting from widely available boronic acids and various [Au(NHC)Cl] (NHC = N-heterocyclic carbene) complexes in unprecedentedly short reaction times and high yields is reported. Successful synthesis of previously non-or poorly accessible complexes exposed fascinating reactivity patterns. Via a gram-scale synthesis, convenient process scalability of the developed protocol was showcased.

Advances in the Synthesis and Applications of N-Heterocyclic Carbene Metal Complexes with a Focus on the Weak Base Route

“…Inspired by their recent exploration of the synthesis of metal-NHC complexes in flow, the Nolan and Stevens groups have developed an efficient and simple microreactor for the preparation of thioureas and selenoureas . These NHC and chalcogen adducts have been widely studied for their properties and coordination chemistry with different transition metals.…”

Gold(I)‐N‐Heterocyclic Carbene Synthons in Organometallic Synthesis

“…This simple continuous flow procedure proved to be compatible with a wide range of aryl-boronic acids and NHCs. [65] With a similar procedure, Pilarski and colleagues were able to obtain N-heterocyclic gold(I)-aryl complexes using pre-synthesized triol-boronates of the type K[ArB(triol)] and [Au(IPr)Cl] (1) as starting materials (Scheme 26E). [66] The reaction proceeds at room temperature, in green solvents (2-MeTHF) and gave a wide range of products in high yield, displaying notable functional group tolerance.…”

Continuous Flow Synthesis of NHC‐Coinage Metal Amido and Thiolato Complexes: A Mechanism‐based Process Development

“…We have recently developed a scalable continuous flow procedure – inspired by the weak base batch protocol – for the synthesis of NHC‐copper(I), ‐gold(I) and ‐palladium(II) complexes from the corresponding imidazolium salt and metal precursor, in unprecedentedly short reaction times [18] . The efficacy of this process to access other complexes was further assessed in the synthesis of a range of gold(I)‐aryl complexes [19] . Encouraged by these initial findings, we hypothesized that the use of continuous flow protocols towards N−H and S−H activation, in a way to further demonstrate the weak base versatility and potential, could further capitalize on our mechanistic understanding of the underlying chemistry to provide easy access to complexes possessing catalytic and photochemical potential.…”

“…[18] The efficacy of this process to access other complexes was further assessed in the synthesis of a range of gold(I)-aryl complexes. [19] Encouraged by these initial findings, we hypothesized that the use of continuous flow protocols towards NÀ H and SÀ H activation, in a way to further demonstrate the weak base versatility and potential, could further capitalize on our mechanistic understanding of the underlying chemistry to provide easy access to complexes possessing catalytic and photochemical potential. We now report on the continuous synthesis of coinage metal-carbazolyl and -thiolato complexes as a proof-of-concept showcasing the synthetic potential of simple, mechanistically based flow processes.…”