Continuous decoupled redox electrochemical CO capture.

Electrochemical CO capture driven by renewable electricity holds significant potential for efficient decarbonization. However, the widespread adoption of this approach is currently limited by issues such as instability, discontinuity, high energy demand, and challenges in scaling up. In this study, we propose a scalable strategy that addresses these limitations by transforming the conventional single-step electrochemical redox reaction into a stepwise electrochemical-chemical redox process.

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation.

The rising popularity of bioconjugate therapeutics has led to growing interest in late-stage functionalization (LSF) of peptide scaffolds. α,β-Unsaturated amino acids like dehydroalanine (Dha) derivatives have emerged as particularly useful structures, as the electron-deficient olefin moiety can engage in late-stage functionalization reactions, like a Giese-type reaction. Cheap and widely available building blocks like organohalides can be converted into alkyl radicals by means of photoinduced silane-mediated halogen-atom transfer (XAT) to offer a mild and straightforward methodology of alkylation.

Light-assisted carbon dioxide reduction in an automated photoreactor system coupled to carbonylation chemistry.

Continuous-flow methodologies offer promising avenues for sustainable processing due to their precise process control, scalability, and efficient heat and mass transfer. The small dimensions of continuous-flow reactors render them highly suitable for light-assisted reactions, as can be encountered in carbon dioxide hydrogenations. In this study, we present a reactor system emphasizing reproducibility, modularity, and automation, facilitating streamlined screening of conditions and catalysts for these processes.

Enhancing electrochemical reactions in organic synthesis: the impact of flow chemistry.

Utilizing electrons directly offers significant potential for advancing organic synthesis by facilitating novel reactivity and enhancing selectivity under mild conditions. As a result, an increasing number of organic chemists are exploring electrosynthesis. However, the efficacy of electrochemical transformations depends critically on the design of the electrochemical cell.

In-Flow Generation of Thionyl Fluoride (SOF) Enables the Rapid and Efficient Synthesis of Acyl Fluorides from Carboxylic Acids.

Herein, we report an approach for generating thionyl fluoride (SOF) from the commodity chemicals thionyl chloride (SOCl) and potassium fluoride (KF). The methodology relies on a microfluidic device that can efficiently produce and dose this toxic gaseous reagent under extremely mild and safe conditions. Subsequently, the in situ-generated thionyl fluoride is reacted with an array of structurally and electronically differing carboxylic acids, leading to the direct and efficient synthesis of highly sought-after acyl fluorides.

A unified flow strategy for the preparation and use of trifluoromethyl-heteroatom anions.

The trifluoromethyl group (CF) is a key functionality in pharmaceutical and agrochemical development, greatly enhancing the efficacy and properties of resulting compounds. However, attaching the CF group to heteroatoms such as sulfur, oxygen, and nitrogen poses challenges because of the lack of general synthetic methods and reliance on bespoke reagents. Here, we present a modular flow platform that streamlines the synthesis of heteroatom-CF motifs.

C1-4 Alkylation of Aryl Bromides with Light Alkanes enabled by Metallaphotocatalysis in Flow.

The homologous series of gaseous C1-4 alkanes represents one of the most abundant sources of short alkyl fragments. However, their application in synthetic organic chemistry is exceedingly rare due to the challenging C-H bond cleavage, which typically demands high temperatures and pressures, thereby limiting their utility in the construction of complex organic molecules. In particular, the formation of C(sp)-C(sp) bonds is crucial for constructing biologically active molecules, including pharmaceuticals and agrochemicals.

Visible light-induced halogen-atom transfer by N-heterocyclic carbene-ligated boryl radicals for diastereoselective C(sp)-C(sp) bond formation.

Photoinduced halogen-atom transfer (XAT) has rapidly emerged as a programmable approach to generate carbon-centered radical intermediates, mainly relying on silyl and α-aminoalkyl radicals as halogen abstractors. More recently, ligated boryl radicals have also been proposed as effective halogen abstractors under visible-light irradiation. In this study, we describe the use of this approach to enable C(sp)-C(sp) bond formation radical addition of carbon-centered radicals generated XAT onto chloroalkynes.

C(sp)-H sulfinylation of light hydrocarbons with sulfur dioxide via hydrogen atom transfer photocatalysis in flow.

Sulfur-containing scaffolds originating from small alkyl fragments play a crucial role in various pharmaceuticals, agrochemicals, and materials. Nonetheless, their synthesis using conventional methods presents significant challenges. In this study, we introduce a practical and efficient approach that harnesses hydrogen atom transfer photocatalysis to activate volatile alkanes, such as isobutane, butane, propane, ethane, and methane.

Graphitic Carbon Nitride as a Photocatalyst for Decarboxylative C(sp)-C(sp) Couplings via Nickel Catalysis.

The development of robust and reliable methods for the construction of C(sp)-C(sp) bonds is vital for accessing an increased array of structurally diverse scaffolds in drug discovery and development campaigns. While significant advances towards this goal have been achieved using metallaphotoredox chemistry, many of these methods utilise photocatalysts based on precious-metals due to their efficient redox processes and tuneable properties. However, due to the cost, scarcity, and toxicity of these metals, the search for suitable replacements should be a priority.

Rapid and scalable photocatalytic C(sp)-C(sp) Suzuki-Miyaura cross-coupling of aryl bromides with alkyl boranes.

In recent years, there has been a growing demand for drug design approaches that incorporate a higher number of sp-hybridized carbons, necessitating the development of innovative cross-coupling strategies to reliably introduce aliphatic fragments. Here, we present a powerful approach for the light-mediated B-alkyl Suzuki-Miyaura cross-coupling between alkyl boranes and aryl bromides. Alkyl boranes were easily generated via hydroboration from readily available alkenes, exhibiting excellent regioselectivity and enabling the selective transfer of a diverse range of primary alkyl fragments onto the arene ring under photocatalytic conditions.

Photocatalytic Functionalization of Dehydroalanine-Derived Peptides in Batch and Flow.

Unnatural amino acids, and their synthesis by the late-stage functionalization (LSF) of peptides, play a crucial role in areas such as drug design and discovery. Historically, the LSF of biomolecules has predominantly utilized traditional synthetic methodologies that exploit nucleophilic residues, such as cysteine, lysine or tyrosine. Herein, we present a photocatalytic hydroarylation process targeting the electrophilic residue dehydroalanine (Dha).

Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes.

In contemporary drug discovery, enhancing the sp-hybridized character of molecular structures is paramount, necessitating innovative synthetic methods. Herein, we introduce a deoxygenative cross-electrophile coupling technique that pairs easily accessible carboxylic acid-derived redox-active esters with aldehyde sulfonyl hydrazones, employing Eosin Y as an organophotocatalyst under visible light irradiation. This approach serves as a versatile, metal-free C(sp)-C(sp) cross-coupling platform.

Automated self-optimization, intensification, and scale-up of photocatalysis in flow.

The optimization, intensification, and scale-up of photochemical processes constitute a particular challenge in a manufacturing environment geared primarily toward thermal chemistry. In this work, we present a versatile flow-based robotic platform to address these challenges through the integration of readily available hardware and custom software. Our open-source platform combines a liquid handler, syringe pumps, a tunable continuous-flow photoreactor, inexpensive Internet of Things devices, and an in-line benchtop nuclear magnetic resonance spectrometer to enable automated, data-rich optimization with a closed-loop Bayesian optimization strategy.

Modular synthesis of congested β-amino acids the merger of photocatalysis and oxidative functionalisations.

A two-step protocol for the modular synthesis of β- and α-quaternary β-amino acid derivatives is reported. The key steps are a photocatalytic hydroalkylation reaction, followed by an oxidative functionalisation to access -protected β-amino acids, esters, and amides. This strategy can be effectively scaled up continuous-flow technology.

Multiphasic Continuous-Flow Reactors for Handling Gaseous Reagents in Organic Synthesis: Enhancing Efficiency and Safety in Chemical Processes.

The use of reactive gaseous reagents for the production of active pharmaceutical ingredients (APIs) remains a scientific challenge due to safety and efficiency limitations. The implementation of continuous-flow reactors has resulted in rapid development of gas-handling technology because of several advantages such as increased interfacial area, improved mass- and heat transfer, and seamless scale-up. This technology enables shorter and more atom-economic synthesis routes for the production of pharmaceutical compounds.

Solar-Driven Continuous CO Reduction to CO and CH using Heterogeneous Photothermal Catalysts: Recent Progress and Remaining Challenges.

The urgent need to reduce the carbon dioxide level in the atmosphere and keep the effects of climate change manageable has brought the concept of carbon capture and utilization to the forefront of scientific research. Amongst the promising pathways for this conversion, sunlight-powered photothermal processes, synergistically using both thermal and non-thermal effects of light, have gained significant attention. Research in this field focuses both on the development of catalysts and continuous-flow photoreactors, which offer significant advantages over batch reactors, particularly for scale-up.

Accelerated Electrophotocatalytic C(sp )-H Heteroarylation Enabled by an Efficient Continuous-Flow Reactor.

Electrophotocatalytic transformations are garnering attention in organic synthesis, particularly for accessing reactive intermediates under mild conditions. Moving these methodologies to continuous-flow systems, or flow ElectroPhotoCatalysis (f-EPC), showcases potential for scalable processes due to enhanced irradiation, increased electrode surface, and improved mixing of the reaction mixture. Traditional methods sequentially link photochemical and electrochemical reactions, using flow reactors connected in series, yet struggle to accommodate reactive transient species.

Efficient C(sp )-H Carbonylation of Light and Heavy Hydrocarbons with Carbon Monoxide via Hydrogen Atom Transfer Photocatalysis in Flow.

Despite their abundance in organic molecules, considerable limitations still exist in synthetic methods that target the direct C-H functionalization at sp -hybridized carbon atoms. This is even more the case for light alkanes, which bear some of the strongest C-H bonds known in Nature, requiring extreme activation conditions that are not tolerant to most organic molecules. To bypass these issues, synthetic chemists rely on prefunctionalized alkyl halides or organometallic coupling partners.

Ni-Catalyzed Electro-Reductive Cross-Electrophile Couplings of Alkyl Amine-Derived Radical Precursors with Aryl Iodides.

In recent years, the "Escape-from-Flatland" trend has prompted the synthetic community to develop a set of cross-coupling strategies to introduce sp-carbon-based fragments in organic compounds. This study presents a novel nickel-catalyzed electrochemical methodology for reductive cross-electrophile coupling. The method enables C(sp)-C(sp) linkages using inexpensive amine-derived radical precursors and aryl iodides.

A field guide to flow chemistry for synthetic organic chemists.

Flow chemistry has unlocked a world of possibilities for the synthetic community, but the idea that it is a mysterious "black box" needs to go. In this review, we show that several of the benefits of microreactor technology can be exploited to push the boundaries in organic synthesis and to unleash unique reactivity and selectivity. By "lifting the veil" on some of the governing principles behind the observed trends, we hope that this review will serve as a useful field guide for those interested in diving into flow chemistry.

Scale-Up of Photochemical Reactions: Transitioning from Lab Scale to Industrial Production.

In the past two decades, we have witnessed a rapid emergence of new and powerful photochemical and photocatalytic synthetic methods. Although these methods have been used mostly on a small scale, there is a growing need for efficient scale-up of photochemistry in the chemical industry. This review summarizes and contextualizes the advancements made in the past decade regarding the scale-up of photo-mediated synthetic transformations.

Photoinduced Halogen-Atom Transfer by -Heterocyclic Carbene-Ligated Boryl Radicals for C(sp)-C(sp) Bond Formation.

Herein, we present a comprehensive study on the use of -heterocyclic carbene (NHC)-ligated boryl radicals to enable C(sp)-C(sp) bond formation under visible-light irradiation via Halogen-Atom Transfer (XAT). The methodology relies on the use of an acridinium dye to generate the boron-centered radicals from the corresponding NHC-ligated boranes via single-electron transfer (SET) and deprotonation. These boryl radicals subsequently engage with alkyl halides in an XAT step, delivering the desired nucleophilic alkyl radicals.

Photocatalytic Alkylation of C(sp )-H Bonds Using Sulfonylhydrazones.

The ability to construct C(sp )-C(sp ) bonds from easily accessible reagents is a crucial, yet challenging endeavor for synthetic organic chemists. Herein, we report the realization of such a cross-coupling reaction, which combines N-sulfonyl hydrazones and C(sp )-H donors through a diarylketone-enabled photocatalytic hydrogen atom transfer and a subsequent fragmentation of the obtained alkylated hydrazide. This mild and metal-free protocol was employed to prepare a wide array of alkyl-alkyl cross-coupled products and is tolerant of a variety of functional groups.