Flow chemistry articles from across Nature Portfolio

Flavin-based biocatalysis using flavin mononucleotide (FMN) cofactor attracts significant attention for its application in asymmetric alkene reduction and various other reactions, however, the scale-up of flavin-based biocatalysis in flow remains unexplored. Here, the authors develop a closed-loop flow platform for H₂-driven regeneration of cofactor FMNH₂ and ene-reduction using immobilized Old Yellow Enzyme, achieving >99% conversion of ketoisophorone to levodione.

Microflow catalysis represents a cutting-edge method for advancing chemical synthesis and manufacturing, though developing efficient and stable multiphase catalysts remains challenging. Here the authors demonstrate the incorporation of amine-containing metal-organic cages into automated microfluidic reactors through covalent bonds, facilitating highly continuous flow catalysis.

De novo syntheses of 1,2-arylheteroaryl ethanes, key scaffolds in drug discovery, are challenging, typically relying on pre-functionalized synthons, harsh conditions and multi-step processes. Now a modular assembly of arenes, ethylene and heteroarenes yields diverse drug-like 1,2-arylheteroaryl ethanes, highlighting the importance of radical polarity matching in selective multi-component couplings.

Sulfur-containing scaffolds originating from small alkyl fragments play a crucial role in various pharmaceuticals, agrochemicals, and materials, but their synthesis presents significant challenges. Herein, the authors report the photocatalytic conversion of C(sp3)–H bonds originating from lightweight alkanes into alkyl sulfinates, employing SO2.

Optimizing the transport, mobility and diffusion of reactants and intermediates in a confined space can accelerate reactions. Here the authors study the reaction of highly reactive intermediates such as short-lived cationic and anionic species in a flow reactor.

Stereoselective production of trans-4-substituted cyclohexane-1-amines—including a key intermediate in the synthesis of antipsychotic drug cariprazine—remains challenging. Here, the authors develop a process catalyzed by a single transaminase to produce trans-4-substituted cyclohexane-1-amines from the corresponding cis/trans-diastereomeric mixtures via a cis-deamination approach in continuous-flow, to achieve a dynamic cis-to-trans isomerization.

In this Issue, we focus on reaction outcomes which are unique to flow setups and their application in synthesis.

Flow chemistry provides a platform for the α-metallation and functionalization of tetrahydrofuran (THF).

Small-molecule drug discovery and development is limited by the ability of chemists to readily synthesize and purify new compounds with suitable chemical diversity. Now, a new twist on solid-phase chemical synthesis has enabled rapid and simplified synthesis of pharmaceutically relevant small molecules.

Fusion systems have been designed that link enzymes to cofactors and immobilization modules through appropriate synthetic spacers. These modular biocatalysts (assembling catalysis, cofactor provision/regeneration and assisted immobilization) are suited to heterogeneous biocatalysis systems and can be efficiently used in continuous flow reactors.

A rapid synthesis of the antibacterial drug linezolid using flow chemistry has been reported that does not require isolation or purification of any intermediates and is completed in seven synthetic steps