Microwave‐Assisted Suzuki Coupling Reactions with an Encapsulated Palladium Catalyst for Batch and Continuous‐Flow Transformations

Abstract

This article describes the design, optimisation and development of a Suzuki cross-coupling protocol mediated by an efficient palladium-encapsulated catalyst (Pd EnCat) under microwave irradiation. The methodology has been used in both batch mode for classical library preparation and in continuous-flow applications furnishing multigram quantities of material. Described is a method that uses direct focused microwave heating whilst applying an external cooling source. This enables a lower than normal bulk temperature to be maintained throughout the reaction period leading to significant improvements in the overall yield and purity of the reaction products. Additional aspects of this novel heating protocol are discussed in relation to the prolonged lifetime and enhanced reactivity of the immobilised catalyst system.

Chemical reaction engineering, process design and scale-up issues at the frontier of synthesis: Flow chemistry

“…MW-assisted Suzuki-Miyaura coupling using an encapsulated palladium catalyst has been also proposed [31]. The direct focused MW heating was coupled with an external cooling source.…”

Accessing Novel Process Windows in a High‐Temperature/Pressure Capillary Flow Reactor

“…Traditionally, most synthetic transformations performed in microreactors have involved ambient or even low-temperature conditions in order to safely conduct highly exothermic reactions [7][8][9][10][11][12][13][14][15][16][17][18][19]. More recently, following the concepts of "Process Intensification" and "Novel Process Windows", flow chemistry at elevated temperature conditions in sealed/pressurized microreaction devices [20][21][22][23][24][25][26] and related continuous flow reactors [27][28][29][30][31][32][33][34][35][36][37][38], have been reported, although the number of publications describing synthetically valuable transformations in a genuine combined high-temperature and high-pressure flow regime, i.e., > 200°C and > 50 bar, is rather limited, with most applications focusing on the generation of high-temperature or supercritical water (scH 2 O) [39][40][41][42][43].…”

Palladium(0) Nanoparticles on Glass‐Polymer Composite Materials as Recyclable Catalysts: A Comparison Study on their Use in Batch and Continuous Flow Processes

“…[37] Several recent publications have demonstrated the feasibility and benefits of carrying out metal-mediated flow chemistry under microwave conditions, although the influence of microwave irradiation on the heterogeneous metal catalyst itself has not been studied in detail. [38] One of the advantages of microwave dielectric heating over conventional heating in the work described here is the fact that strongly absorbing materials such as metal particles can be heated selectively in a reaction mixture. [36,39] It can therefore be imagined that the intrinsic temperature localized around those particles is significantly higher than that of the bulk solution.…”