Charlotte. E. Willans

The platform intermediate K ₂ [Ir(OH) ₆ ] is isolated from complex chloroiridate mixtures and can be used to make technologically useful Ir( iii ) cooridnation complexes.

Aryl halides are convenient, stable precursors to synthetically versatile aryl radicals, but the generation of the latter typically requires either stoichiometric tin/silicon reagents or precious metal photocatalysts, in both cases typically under conditions of high dilution. Here, we show that tertiary amines can mediate reductive cyclisations of aryl halides under photochemical conditions by (i) facilitating generation of aryl radicals through formation of photo‐active halogen bonding complexes, and (ii) acting as a source of mild terminal reductant. The absence of strong stoichiometric reductants allows the reactions to be conducted under untypically concentrated conditions without competing bimolecular aryl halide reduction, with associated benefits for productivity and sustainability metrics.

Exploiting continuous flow for optimising Ni-catalyzed Suzuki–Miyaura reactions; a versatile, sustainable methodology translated directly to the synthesis of complex APIs savolitinib and baxdrostat.

Polymer supported Mn acts as an efficient catalyst in the hydrosilylation of aldehydes, esters and an amide.

Following Ni-catalysed Suzuki–Miyaura cross coupling reactions, Ni is electrochemically removed on to the cathode, offering potential for recovery and reuse.

A theoretical and practical frameworkfor predicting, rationalizing,and adapting water-accelerated reactions into holistically sustainableflow processes has been demonstrated. Water-accelerated reactions, wherein at least one organicreactantis not soluble in water, are an important class of organic reactions,with a potentially pivotal impact on sustainability of chemical manufacturingprocesses. However, mechanistic understanding of the factors controllingthe acceleration effect has been limited, due to the complex and variedphysical and chemical nature of these processes. In this study, atheoretical framework has been established to calculate the rate accelerationof known water-accelerated reactions, giving computational estimationsof the change to Delta G (double dagger) whichcorrelate with experimental data. In-depth study of a Henry reactionbetween N-methylisatin and nitromethane using ourframework led to rationalization of the reaction kinetics, its lackof dependence on mixing, kinetic isotope effect, and different salteffects with NaCl and Na2SO4. Based on thesefindings, a multiphase flow process which includes continuous phaseseparation and recycling of the aqueous phase was developed, and itssuperior green metrics (PMI-reaction = 4 and STY = 0.64 kg L-1 h(-1)) were demonstrated. These findings form theessential basis for further in silico discovery and development ofwater-accelerated reactions for sustainable manufacturing.

A novel semi-automated, high-throughput computational workflow for ligand/catalyst discovery based on the Cambridge Structural Database is reported.

The development of an integrated multistep flow platform that incorporates high-throughput electrochemical synthesis of metal catalysts and catalysis screening is described. Ligand libraries can be screened through the implementation of an autosampler, and online HPLC analysis facilitates continuous monitoring of the reaction. The equipment is controlled via a computer which enables the process to be automated, with the platform running ligand/catalysis screens autonomously. The platform has been validated using a ubiquitous Cu–NHC catalysed click reaction, with conditions chosen so that the reaction does not run at full conversion, which allows the effect of different ligand precursors to be observed. An efficient cleaning step is crucial to the reproducibility of reactions, and alternating polarity ensures the long-term stability of the electrochemical reactor. This technology will enable the profiling of catalysts in continuous systems and accelerate the process of developing more sustainable base-metal catalysts in manufacturing processes.