Recent research endeavors have established that the mechanochemical activation of piezoelectric materials can open new avenues in redox chemistry. Impact forces, such as those imparted by a ball ...mill, have been shown to transform piezoelectric materials such as barium titanate (BaTiO3) into a highly polarized state, which can then donate an electron to a suitable oxidant and receive an electron from a suitable reductant, mimicking established photoredox catalytic cycles. Proof‐of‐concept studies have elucidated that mechanoredox chemistry holds great potential in sustainable and efficient radical‐based synthesis.
The application of mechanical force to a material can lead to the generation of electric charge; piezoelectricity. For the first time, this effect has been harnessed and applied to radical reactions under ball‐milling conditions, this Concept briefly describes the first appearances of this ground‐breaking technique in the literature.
Mechanochemistry is becoming more widespread as a technique for molecular synthesis with new mechanochemical reactions being discovered at increasing frequency. Whilst mechanochemical methods are ...solvent free and can therefore lead to improved sustainability metrics, it is more likely that the significant differences between reaction outcomes, reaction selectivities and reduced reaction times will make it a technique of interest to synthetic chemists. Herein, we provide an overview of mechanochemistry reaction examples, with 'direct' comparators to solvent based reactions, which collectively seemingly show that solid state grinding can lead to reduced reaction times, different reaction outcomes in product selectivity and in some instances different reaction products, including products not accessible in solution.
Mechanochemistry is becoming more widespread as a technique for molecular synthesis with new mechanochemical reactions being discovered at increasing frequency. This perspective explores what more it can offer, aside from the clear benefit of reduced solvent consumption.
Sulfonamides are key motifs in pharmaceuticals and agrochemicals, spurring the continuous development of novel and efficient synthetic methods to access these functional groups. Herein, we report an ...environmentally benign electrochemical method which enables the oxidative coupling between thiols and amines, two readily available and inexpensive commodity chemicals. The transformation is completely driven by electricity, does not require any sacrificial reagent or additional catalysts and can be carried out in only 5 min. Hydrogen is formed as a benign byproduct at the counter electrode. Owing to the mild reaction conditions, the reaction displays a broad substrate scope and functional group compatibility.
A form independent activation of zinc, concomitant generation of organozinc species and engagement in a Negishi cross‐coupling reaction via mechanochemical methods is reported. The reported method ...exhibits a broad substrate scope for both C(sp3)–C(sp2) and C(sp2)–C(sp2) couplings and is tolerant to many important functional groups. The method may offer broad reaching opportunities for the in situ generation organometallic compounds from base metals and their concomitant engagement in synthetic reactions via mechanochemical methods.
Complement the synthetic toolkit: A form‐independent activation of zinc, concomitant generation of organozinc species, and engagement in a Negishi cross‐coupling reaction via mechanochemical methods is reported. The reported method exhibits a broad substrate scope for both C(sp3)–C(sp2) and C(sp2)–C(sp2) couplings.
A reaction manifold has been discovered in which the chemoselectivity can be altered by switching between neat milling and liquid assisted grinding (LAG) with polar additives. After investigation of ...the reaction mechanism, it has been established that this switching in reaction pathway is due to the neat mechanochemical conditions exhibiting different kinetics for a key step in the transformation. This proof of concept study demonstrates that mechanochemistry can be used to trap the kinetic product of a reaction. It is envisaged that, if this concept can be successfully applied to other transformations, novel synthetic processes could be discovered and known reaction pathways perturbed or diverted.
Shaking things up: A reaction manifold has been discovered in which the covalent structure of the obtained product is dependent on whether the reaction is conducted under neat milling or in solution. Further investigation has highlighted that the kinetic product is produced by milling and the thermodynamic by solution‐phase reaction.
The development and application of continuous flow chemistry methods for synthesis is a rapidly growing area of research. In particular, natural products provide demanding challenges to this ...developing technology. This review highlights successes in the area with an emphasis on new opportunities and technological advances.
The development and application of continuous flow chemistry methods for synthesis have been ongoing in research laboratories for more than a decade, during which time a number of natural product syntheses have been investigated and reported using such tools.
A means to trifluoromethylate: The beneficial properties imparted by the trifluoromethylation of aromatic compounds continue to drive the discovery of novel reagents and reactions for the late‐stage ...introduction of such moieties. Highlighted here is the recently discovered Sandmeyer trifluoromethylation approach, which now permits aromatic amines to be substrates in a direct trifluoromethylation strategy.
Rapid and wide-ranging developments have established mechanochemistry as a powerful avenue in sustainable organic synthesis. This is primarily due to unique opportunities which have been offered in ...solvent-free - or highly solvent-minimised - reaction systems. Nevertheless, despite elegant advances in ball-milling technology, limitations in scale-up still remain. This tutorial review covers the first reports into the translation from "batch-mode" ball-milling to "flow-mode" reactive extrusion, using twin-screw extrusion.
Reactive extrusion provides a scale-up opportunity to turn a mechanochemical process from a ball-mill into continuous flow. This tutorial review summarises some of the early ground-breaking work in this area.
We have identified an example of a mechanochemically milled organic reaction where liquid-assisted grinding controls the selectivity, such a phenomenon has not been reported/observed before. It was ...found that upon milling dibenzoylmethane with Selectfluor in the absence of any solvent, a 3 : 1 ratio of monofluorinated : difluorinated product was observed. Whereas, addition of 0.125 mL of acetonitrile ( similar to 10% of the total volume of materials present) to the ground reaction mixture afforded 50 : 1 selectivity. Furthermore, this phenomenon is applicable to a small range of diketone substrates thus far explored. Additionally, we have demonstrated that difluorination can be achieved by simply switching from adding acetonitrile to addition of sodium carbonate. Most notable, in the latter case, is the reduced reaction time compared to a conventional solvent approach, 2 hours in the mill and 24 hours in the flask.
A manganese-catalyzed electrochemical deconstructive chlorination of cycloalkanols has been developed. This electrochemical method provides access to alkoxy radicals from alcohols and exhibits a ...broad substrate scope, with various cyclopropanols and cyclobutanols converted into synthetically useful β- and γ-chlorinated ketones (40 examples). Furthermore, the combination of recirculating flow electrochemistry and continuous inline purification was employed to access products on a gram scale.
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