# Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling in Continuous Flow
## 1 Introduction  
Among the main reactions in organic chemistry, C-C bond formation via a cross-coupling reaction catalyzed by transition metals is undoubtedly the most important and has been exploited very widely in the recent years. Palladium, the most widely used metal, enables the synthesis of complex and functionalized organic molecules and its chemistry possesses different interesting facets such as heterogeneous and homogeneous catalysis under mild experimental conditions compatible with many functional groups [1; 2; 3; 4; 5]. Several palladium catalyzed cross-coupling reactions such as [PERSON] [6; 7; 8; 9; 10; 11], [PERSON] [12; 13; 14; 15; 16], Songosharina [17; 18; 19; 20; 21], [PERSON] [22; 23; 24; 25], Hiyama [26], Negishi [27], [PERSON] [28], [PERSON] [29] and Buchwald-Hartwig [30; 31] have been developed over the years.  
Due to current impetus in promoting green chemistry for sustainable development, both for academic and industrial research, chemists have recently established catalytic reactions based on renewable resources, atom economy, less hazardous chemical steps, safer (least toxic) solvents, auxiliaries and alternative technologies such as continuous flow, microwave irradiation, ultrasound irradiation, etc. In the context of green chemistry, catalysis and alternative media, different cross-coupling reactions such as Suzuki-Miyaura in batch reactors have been developed in aqueous media or in water as sole green safer solvent via conventional heating or microwave irradiation [32; 33; 34; 35; 36; 37; 38; 39; 40; 41; 42; 43]. Continuous flow chemistry as alternative technology offers significant processing advantages including improved thermal management, mixing control, application to a wider range of reaction conditions, scalability, energy efficiency, waste reduction, safety, use of heterogeneous catalysis, multistep synthesis and much more [44; 45; 46; 47; 48; 49]. Two different reactors, micro and meso (or flow) reactors, exist and the devices depend on the channeldimensions, from 10 to 300 \(\upmu\)m for the micro reactor (also called milli or mini) and from 300 \(\upmu\)m to more than 5 mm for the meso reactor. Several advantages and disadvantages are associated with the micro and meso reactors. The main advantages for the micro reactor are the low material input, low waste output, excellent mass transfer properties, fast diffusive mixing and the disadvantages are the low throughput, tendency to channel blockage and high pressure drop. In the case of solid handling due to confined conditions and increasing of the concentration to have a better productivity, the use of continuous sonication could prevent clogging [50]. For the meso reactor, the advantages are the high throughput, low pressure drop and possibility to handle solids for heterogeneous catalysis. Few disadvantages for meso reactors are poor mass transfer property, slower mixing, etc. Different studies have described the theory and practicalities of scaled-out micro and meso reactors but no practical examples of large-scale production have been described. Palladium-catalyzed cross-coupling reactions in continuous flow reactors have been reported in the literature at temperatures higher than 60 \({}^{\circ}\)C [51; 52; 53; 54; 55; 56; 57; 58; 59; 60; 61; 62; 63], while only few studies have described micro and meso reactors for the C-C bond formation at temperature lower than 60 \({}^{\circ}\)C. In parallel with the synthesis of low molecular weight compounds, this technique has been applied by academic and industrial groups for the production of polymers [64; 65; 66; 67]. For the sake of clarity, this review describes continuous flow selective palladium-catalyzed cross-coupling reactions having a good energy efficiency at temperatures ranging between 0 \({}^{\circ}\)C and 80 \({}^{\circ}\)C.