An operationally simple mechanochemical C-S coupling of aryl halides with thiols has been developed. The reaction process operates under bench-top conditions without the requirement for (dry) solvent, inert atmosphere, or catalyst pre-activation. The reaction is finished within three hours. The reaction is demonstrated across a broad range of substrates; the inclusion of zinc metal has been found to be critical in some instances, especially for coupling of alkyl thiols.

The mechanochemical synthesis of 2,4,5,6-tetra­(9H-carbazol-9-yl)­isophthalonitrile and related organic fluorophores/photocatalysts via a solvent-minimized four-fold SNAr pathway is herein described. Employing sodium tert-butoxide as base, and negating the need for any air/moisture-sensitive reaction set-ups, a selection of organic dyes was synthesized in just 1 h using this ball-milling technique. Furthermore, the transformation was then showcased on a multigram scale.

Continuous flow systems offer unique benefits in the generation and manipulation of sensitive reactive intermediates such as ketenes. To this end, the last decade has witnessed the development of continuous flow methods for the generation of ketenes by means of chemical, thermal, and photochemical activation modes. This perspective covers these advances and the downstream reactivity of ketenes in continuous flow technology.

The versatility of olefin metathesis is evident from its successful applications ranging from natural product synthesis to the valorization of renewable feedstocks. On the other side, flow chemistry has recently gained particular interest among the synthetic community, offering valuable alternatives to classic batch chemistry and paving the way to the development of new transformations. The application of continuous flow to olefin metathesis represents one of the most promising evolutions in the field at the interface of industrially relevant synthesis and reactor engineering, significantly improving some of the typical problems such as undesired self-reactions and ethylenemediated catalyst de-activation. This review aims to provide a small survey covering the major aspects of those techniques which we hope may be of interest for the chemical community, but also those interested in catalysis, continuous processing, enabling technologies and reactor design.

A flow chemistry process for the generation and use of acylketene precursors through extrusion of nitrogen gas is reported. Key to the development of a suitable continuous protocol is the balance of reaction concentration against pressure in the flow reactor. The resulting process enables access to intercepted acylketene scaffolds using volatile amine nucleophiles and has been demonstrated on the gram scale. Thermal gravimetric analysis was used to guide the temperature set point of the reactor coils for a variety of acyl ketene precursors. The simultaneous generation and reaction of two reactive intermediates (both derived from nitrogen extrusion) is demonstrated.