39 research outputs found
Mechanochemical SimmonsâSmith cyclopropanation via ball-milling-enabled activation of zinc(0)
The bulk solvent-free synthesis of cyclopropanes via a ball-milling-enabled SimmonsâSmith reaction is herein described
Evolution of Solid Processing Methods in Continuous Flow Technology: Reactive Extrusion
The frustrations of precipitation, fouling and blockages of liquid-based flow reactors is familiar to all researchers that have worked with continuous flow equipment. There have been many innovative solutions to try and circumvent this issue. This short review will highlight the emerging technique of mechanochemistry and reactive extrusion as a continuous process that can directly work on solid (and liquid) materials and elicit chemical transformations
Regioselective Transition-Metal-Catalyzed CâH Functionalization of Anilines
Anilines are a vital synthetic core of pharmaceuticals, agrochemicals, natural products and building blocks. Metal-catalyzed CâH functionalization has emerged as a powerful tool to derivatize biologically relevant molecules. To this end, the derivation of anilines via catalytic CâH functionalization has been the subject of important new synthetic methodology. This review focuses on the tactics used to allow regioselective CâH functionalization of anilines.1 Introduction2 ortho-Selective CâH Functionalization2.1 Palladium2.2 Rhodium2.3 Ruthenium2.4 Nickel3 meta-Selective CâH Functionalization4 para-Selective CâH Functionalization5 Conclusion</jats:p
Temperature-Controlled Mechanochemistry for the Nickel-Catalyzed Suzuki-Miyaura-Type Coupling of Aryl Sulfamates via Ball Milling and Twin-Screw Extrusion
The use of temperature-controlled mechanochemistry to enable the mechanochemical nickel-catalyzed Suzuki-Miyaura coupling is herein described. Transitioning from a capricious room-temperature protocol, through to a heated, PID-controlled programmable jar heater manifold was required to deliver an efficient method for the coupling of aryl sulfamates (derived from ubiquitous phenols) and aryl boronic acid species. Furthermore, this process is conducted using a base-metal nickel catalyst, in the absence of bulk solvent, and in the absence of air/moisture sensitive reaction set-ups. This methodology is showcased through translation to large-scale twin-screw extrusion methodology enabling 200-fold scale increase, producing decagram quantities of C-C coupled material
Beyond C2 and C3: Transition-Metal-Catalyzed CâH Functionalization of Indole
The indole scaffold will continue to play a vital part in the future of drug discovery and agrochemical development. Because of this, the necessity for elegant techniques to enable selective CâH functionalization is vast. Early developments have led to primarily C2 and C3 functionalization because of the inherent reactivity of the pyrrole ring. Despite this, elegant methods have been developed to enable selective CâH functionalization on the benzenoid moiety at C4, C5, C6, and C7. This review focuses on the contributions made in benzenoid CâH functionalization of indoles and other related heteroaromatics such as carbazoles
Continuous flow mechanochemistry: reactive extrusion as an enabling technology in organic synthesis
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
A ball-milling-enabled cross-electrophile coupling
The nickel-catalyzed cross-electrophile coupling of aryl halides and alkyl halides enabled by ball-milling is herein described. Under a mechanochemical manifold, the reductive CâC bond formation was achieved in the absence of bulk solvent and air/moisture sensitive setups, in reaction times of 2 h. The mechanical action provided by ball milling permits the use of a range of zinc sources to turnover the nickel catalytic cycle, enabling the synthesis of 28 cross-electrophile coupled products
Remote C6-Selective Ruthenium-Catalyzed C-H Alkylation of Indole Derivatives via Ï-Activation
The
site-selective functionalization of an indole template offers
exciting possibilities for the derivatization of molecules with useful
biological properties. Herein, we report the remote C6-selective CâH
alkylation of indole derivatives enabled by dual cyclometalation/redox
ruthenium catalysis. Remote alkylation was achieved using <i>N</i>-pyrimidinyl indoles with an ancillary ester directing
group at the C3 position. This ancillary directing group proved pivotal
to reactivity at C6, with yields up to 92% achieved. A one-pot procedure
to install this directing group followed by remote C6 functionalization
has also been reported; both processes are shown to proceed via ruthenium
redox catalysis. Computationally calculated Fukui indices elucidated
that the C6 position was the most reactive vacant CâH site
toward potential functionalization. When this investigation was coupled
with deuterium incorporation studies, a C2-cyclometalation/remote
Ï-activation pathway was deduced
Formation and utility of reactive ketene intermediates under continuous flow conditions
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
Continuous flow mechanochemistry: reactive extrusion as an enabling technology in organic synthesis
apid 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 â or highly solvent-minimised â 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 âbatch-modeâ ball-milling to âflow-modeâ reactive extrusion, using twin-screw extrusion