Organometallic Flow Chemistry

Table of Contents

1. Frontmatter

2. Beyond Organometallic Flow Chemistry: The Principles Behind the Use of Continuous-Flow Reactors for Synthesis

   Timothy Noël, Yuanhai Su, Volker Hessel

   Abstract

   Flow chemistry is typically used to enable challenging reactions which are difficult to carry out in conventional batch equipment. Consequently, the use of continuous-flow reactors for applications in organometallic and organic chemistry has witnessed a spectacular increase in interest from the chemistry community in the last decade. However, flow chemistry is more than just pumping reagents through a capillary and the engineering behind the observed phenomena can help to exploit the technology’s full potential. Here, we give an overview of the most important engineering aspects associated with flow chemistry. This includes a discussion of mass-, heat-, and photon-transport phenomena which are relevant to carry out chemical reactions in a microreactor. Next, determination of intrinsic kinetics, automation of chemical processes, solids handling, and multistep reaction sequences in flow are discussed. Safety is one of the main drivers to implement continuous-flow microreactor technology in an existing process and a brief overview is given here as well. Finally, the scale-up potential of microreactor technology is reviewed.

3. Organic Photoredox Chemistry in Flow

   Matthew B. Plutschack, Camille A. Correia, Peter H. Seeberger, Kerry Gilmore

   Abstract

   The recent movement toward greener, more sustainable chemistry has led to the emergence of photoredox chemistry, capable of catalyzing a wide berth of chemical transformations by channeling the energy of light to reach otherwise unobtainable levels of reactivity and selectivity. A recent parallel development in the field of flow chemistry has led to the enhancement of reactivity and productivity of these photoredox processes, making it a practical method for organic synthesis. This chapter discusses recent advances in the field of organic photoredox chemistry whose reactivity or productivity has been enhanced by flow chemistry.

4. Organometallic-Catalysed Gas–Liquid Reactions in Continuous Flow Reactors

   Paul Watts

   Abstract

   Continuous flow processing significantly enhances gas–liquid mixing. Given that reactive gases are highly valuable reagents for many chemical transformations, flow reactor technology has been extended to enable gas–liquid reactions to be facilitated. This chapter describes how hydrogenation, hydroformylation and trifluoromethylation reactions may be performed exploiting continuous flow technology.

5. Aerobic Oxidations in Continuous Flow

   Bartholomäus Pieber, C. Oliver Kappe

   Abstract

   In recent years, the high demand for sustainable processes resulted in the development of highly attractive oxidation protocols utilizing molecular oxygen or even air instead of more uneconomic and often toxic reagents. The application of these sustainable, gaseous oxidants in conventional batch reactors is often associated with severe safety risks and process challenges especially on larger scales. Continuous flow technology offers the possibility to minimize these safety hazards and concurrently allows working in high-temperature/high-pressure regimes to access highly efficient oxidation protocols. This review article critically discusses recent literature examples of flow methodologies for selective aerobic oxidations of organic compounds. Several technologies and reactor designs for biphasic gas/liquid as well as supercritical reaction media are presented in detail.

6. Preparation and Use of Organolithium and Organomagnesium Species in Flow

   Aiichiro Nagaki, Jun-Ichi Yoshida

   Abstract

   This chapter presents a brief overview regarding the use of flow microreactors for the preparation and reactions of organometallic species, with special emphasis on the synthetic transformations using highly reactive species such as organolithiums and organomagnesiums that are difficult or impossible to achieve using conventional batch reactors.

7. Preparation of Nanomaterials in Flow at Supercritical Conditions from Coordination Complexes

   Samuel Marre, Cyril Aymonier

   Abstract

   The development of nanosciences and nanotechnologies in the twenty-first century is linked to the progresses made with the nanomaterial synthesis approaches. Control, reproducibility, scalability, and sustainability are the key issues for the design of advanced nanostructured materials. Among the synthesis methods, the supercritical fluid-based flow process presents an efficient alternative for the continuous, controlled, scalable, and sustainable synthesis of nanomaterials, especially from coordination complexes, which is the main topic of this book chapter. First, the supercritical fluids are defined and their specific properties introduced with the possibility to adjust them playing with pressure, temperature, and composition for mixtures. The case of water is also described underlining the remarkable evolution from a polar solvent in normal conditions of pressure and temperature to a nonpolar one at supercritical conditions. After, the typical supercritical flow processes of nanomaterials are technically described in details with the different elements, namely injection, mixers, reactors, and pressure regulators. This allows introducing the main operating parameters giving access to a continuous and control synthesis of nanomaterials by mastering thermodynamics, hydrodynamics, and chemistry. Coupling chemistry of coordination complexes and chemical engineering in supercritical fluids leads to the design of high-quality and unique nanostructures. This is in particular illustrated with the synthesis of nanooxides from flow supercritical sol–gel syntheses. The access to highly crystallized oxides with controlled compositions is discussed with the synthesis of BaTiO₃-based materials. The supercritical route is also a versatile method. Beyond the continuous production of nanooxides, it is also possible to prepare in flow nitrides, sulfides, selenides, phosphides, …, nanocrystals (GaN, CdS, CdSe, InP, …). Adding surfactants in situ or ex situ playing with the process offers the possibility to design hybrid organic/inorganic nanoparticles with a control of the strength of the bond at the interface between the inorganic core and the organic shell. This chapter is ended with the description of supercritical coflow reactors, which allow a high level of control of the synthesis operating conditions. All the bricks are now available from a chemical engineering and coordination complex chemistry point of view to go towards multisteps and one pot processes for the continuous and sustainable design of advanced and multifunctional nanomaterials.

8. Enantioselective Organometallic Catalysis in Flow

   Haruro Ishitani, Yuki Saito, Shū Kobayashi

   Abstract

   Enantioselective chemical transformations using chiral metal catalysts under continuous-flow conditions are described. Although flow methods have several advantages over batch methods in terms of environmental compatibility, efficiency, and safety, synthesis by flow methods is more difficult than by batch methods. Some pioneering efforts on the topic were conducted in the early 1990s; major contributions have been started very recently. While some fruitful results have been reported in enantioselective hydrogenation, other reactions such as enantioselective oxidation, C–X bond formation, and C–C bond formation are still limited. More advances is expected because flow methods are leading candidates for the next generation of manufacturing methods that can mitigate environmental concerns.

9. Catalysis in Flow: Why Leaching Matters

   King Kuok (Mimi) Hii, Klaus Hellgardt

   Abstract

   The ability to deploy heterogeneous catalysts in continuous flow depends on their stability against deactivation and for reactions in the liquid phase (leaching). This article will discuss the current understanding how leaching can affect catalyst activity and deactivation. Future prospects for the development of the field are proposed.

10. Backmatter