Direct Oxidation of Csp3 -H bonds using in Situ Generated Trifluoromethylated Dioxirane in Flow.

A fast, scalable, and safer Csp 3 -H oxidation of activated and un-activated aliphatic chains can be enabled by methyl(trifluoromethyl)dioxirane (TFDO). The continuous flow platform allows the in situ generation of TFDO gas and its rapid reactivity toward tertiary and benzylic Csp3 -H bonds. The process exhibits a broad scope and good functional group compatibility (28 examples, 8-99 %). The scalability of this methodology is demonstrated on 2.5 g scale oxidation of adamantane.

A Hybridised Optimisation of an Automated Photochemical Continuous Flow Reactor.

A new hybridized algorithm that combines process optimisation with response surface mapping was developed and applied in an automated continuous flow reaction. Moreover, a photochemical cascade CSTR was developed and characterised by chemical actinometry, showing photon flux density of ten times greater than previously reported in batch. The success of the algorithm was then evaluated in the aerobic oxidation of sp³ C-H bonds using benzophenone as photosensitizer in the newly developed photo reactor.

Photochemical Homologation for the Preparation of Aliphatic Aldehydes in Flow.

Cheap and readily available aqueous formaldehyde was used as a formylating reagent in a homologation reaction with nonstabilized diazo compounds, enabled by UV photolysis of bench-stable oxadiazolines in a flow photoreactor. Various aliphatic aldehydes were synthesized along with the corresponding derivatized alcohols and benzimidazoles. No transition-metal catalyst or additive was required to affect the reaction, which proceeded at room temperature in 80 min.

Preparation of homoallylic amines via a three-component coupling process.

A three-component synthesis of homoallylic amines is described. The allylboronic species were generated in situ by homologation of vinyl boroxines with trimethylsilyldiazomethane, then followed by trapping of the allylboron intermediate with imines. Twenty-seven compounds were successfully prepared in moderate to high yields. Imines bearing various functional groups were tolerated, including aliphatic, aromatic and heteroaromatic substituents. Further elaboration of some of the homoallylic amines to form azeditines is also reported.

Cyclopropanation using flow-generated diazo compounds.

We have devised a room temperature process for the cyclopropanation of electron-poor olefins using unstabilised diazo compounds, generated under continuous flow conditions. This protocol was applied to a wide range of different diazo species to generate functionalised cyclopropanes which are valuable 3D building blocks.

Autonomous optimisation of a nanoparticle catalysed reduction reaction in continuous flow.

An automated continuous flow reactor system equipped with inline analysis, was developed and applied in the self-optimisation of a nanoparticle catalysed reaction. The system was used to optimise the experimental conditions of a gold nanoparticle catalysed 4-nitrophenol reduction reaction, towards maximum conversion in under 2.5 hours. The data obtained from this optimisation was then used to generate a kinetic model, allowing us to predict the outcome of the reaction under different conditions. By combining continuous flow nanoparticle synthesis with this approach, the development timeline for these emerging catalysts could be significantly accelerated.

Organic photocatalysis for the radical couplings of boronic acid derivatives in batch and flow.

We report an acridium-based organic photocatalyst as an efficient replacement for iridium-based photocatalysts to oxidise boronic acid derivatives by a single electron process. Furthermore, we applied the developed catalytic system to the synthesis of four active pharmaceutical ingredients (APIs). A straightforward scale up approach using continuous flow photoreactors is also reported affording gram an hour throughput.

C-H functionalisation of aldehydes using light generated, non-stabilised diazo compounds in flow.

The difficulty in accessing and safely utilising non-stabilised diazo species has in the past limited the application of this class of compounds. Here we explore further the use of oxadiazolines, non-stabilised diazo precursors which are bench stable, in direct, non-catalytic, aldehyde C-H functionalisation reactions under UV photolysis in flow and free from additives. Commercially available aldehydes are coupled to afford unsymmetrical aryl-alkyl and alkyl-alkyl ketones while mild conditions and lack of transition metal catalysts allow for exceptional functional group tolerance. Examples are given on small scale and in a larger scale continuous production.