Visible light-promoted iron-catalyzed C(sp2)-C(sp3) Kumada cross-coupling in flow

X.-J.W., I.A., J.A., and T.N. would like to acknowledge the European Union for a Marie Curie ITN Grant (Photo4Future, Grant No. 641861). C.S. acknowledges the European Union for a Marie Curie European post-doctoral fellowship (FlowAct, Grant No. 794072). We would like to thank the Engineering and Physical Sciences Research Council for financial support (EP/M02105X/1). C. L. thanks the Prof. & Mrs Purdie Bequests Scholarship and AstraZeneca for his PhD Studentship.A continuous‐flow, visible‐light‐promoted method has been developed to overcome the limitations of iron‐catalyzed Kumada–Corriu cross‐coupling reactions. A variety of strongly electron rich aryl chlorides, previously hardly reactive, could be efficiently coupled with aliphatic Grignard reagents at room temperature in high yields and within a few minutes’ residence time, considerably enhancing the applicability of this iron‐catalyzed reaction. The robustness of this protocol was demonstrated on a multigram scale, thus providing the potential for future pharmaceutical application.Publisher PDFPeer reviewe

The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic, Cardiovascular, and Anthropometric Traits

PMCID: PMC3410907This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Visible-Light Photocatalytic Difluoroalkylation-Induced 1, 2‑Heteroarene Migration of Allylic Alcohols in Batch and Flow

A convenient method for the preparation of sp³-rich heterocycles is reported. The method comprises a photocatalytic difluoroalkylation-induced 1,2-heteroarene migration of allylic alcohols. Here we describe for the first time the benefits of using flow to facilitate such migration reactions, including shorter reaction times, higher selectivities, and opportunities to scale the chemistry

Hydrogen Chloride Gas in Solvent-Free Continuous Conversion of Alcohols to Chlorides in Microflow

Chlorides represent a class of valuable intermediates that are utilized in the preparation of bulk and fine chemicals. An earlier milestone to convert bulk alcohols to corresponding chlorides was reached when hydrochloric acid was used instead of toxic and wasteful chlorinating agents. This paper presents the development of an intensified solvent-free continuous process by using hydrogen chloride gas only. The handling of corrosive hydrogen chloride became effortless when the operating platform was split into dry and wet zones. The dry zone is used to deliver gas and prevent corrosion, while the wet zone is used to carry out the chemical transformation. The use of gas instead of hydrochloric acid allowed a decrease in hydrogen chloride equivalents from 3 to 1.2. In 20 min residence time, full conversion of benzyl alcohol yielded 96 wt % of benzyl chloride in the product stream. According to green chemistry and engineering principles, the developed process is of an exemplary type due to its truly continuous nature, no use of solvent and formation of water as a sole byproduct

Aerobic C–H Olefination of Indoles via a Cross-Dehydrogenative Coupling in Continuous Flow

Herein, we report the first site-selective, Pd­(II)-catalyzed, cross-dehydrogenative Heck reaction of indoles in micro flow. By use of a capillary microreactor, we were able to boost the intrinsic kinetics to accelerate former hour-scale reaction conditions in batch to the minute range in flow. The synergistic use of microreactor technology and oxygen, as both terminal oxidant and mixing motif, highlights the sustainable aspect of this process

Visible-Light Photocatalytic Decarboxylation of α,β-Unsaturated Carboxylic Acids: Facile Access to Stereoselective Difluoromethylated Styrenes in Batch and Flow

The development of synthetic methodologies which provide access to both stereoisomers of α,β-disubstituted olefins is a challenging undertaking. Herein, we describe the development of an operationally simple and stereoselective synthesis of difluoromethylated styrenes via a visible-light photocatalytic decarboxylation strategy using <i>fac</i>-Ir­(ppy)₃ as the photocatalyst. Meta- and para-substituted cinnamic acids provide the expected <i>E</i>-isomer. In contrast, <i>ortho</i>-substituted cinnamic acids yield selectively the less stable <i>Z</i>-product, whereas the <i>E</i>-isomer can be obtained via continuous-flow processing through accurate control of the reaction time. Furthermore, our protocol is amenable to the decarboxylative difluoromethylation of aryl propiolic acids

Flow Synthesis of Diaryliodonium Triflates

A safe and scalable synthesis of diaryliodonium triflates was achieved using a practical continuous-flow design. A wide array of electron-rich to electron-deficient arenes could readily be transformed to their respective diaryliodonium salts on a gram scale, with residence times varying from 2 to 60 s (44 examples)

Visible light-promoted iron-catalyzed C(sp²)-C(sp³) Kumada cross-coupling in flow

A continuous‐flow, visible‐light‐promoted method has been developed to overcome the limitations of iron‐catalyzed Kumada–Corriu cross‐coupling reactions. A variety of strongly electron rich aryl chlorides, previously hardly reactive, could be efficiently coupled with aliphatic Grignard reagents at room temperature in high yields and within a few minutes’ residence time, considerably enhancing the applicability of this iron‐catalyzed reaction. The robustness of this protocol was demonstrated on a multigram scale, thus providing the potential for future pharmaceutical application

Palladium-Catalyzed Aerobic Oxidative Coupling of <i>o</i>‑Xylene in Flow: A Safe and Scalable Protocol for Cross-Dehydrogenative Coupling

Herein, the first continuous cross-dehydrogenative homocoupling of an unactivated arene using oxygen as sole oxidant is reported. Employing microreactor technology which enables the use of elevated temperatures and pressures leads to a boost of the catalytic reaction. Hence, a major reduction in reaction time is achieved. Due to the significance as precursor for MOFs as well as high-tech and high-value polymers, the study focused on the production of 3,4,3′,4′-tetramethyl-biphenyl