Frank Glorius

• Prof. Dr.
• University of Münster

This review provides atomic-level insights into the binding, self-assembly, surface reactions, and electronic properties of N-heterocyclic carbenes on surfaces, emphasizing their potential in surface science and materials design.

Despite their unique physical properties and diverse applications in materials science, poor solubility of polycyclic aromatic hydrocarbons (PAHs) limits further fine-tuning and investigation of these systems. Herein, we report a sulfoniumization strategy to solubilize and functionalize a diverse range of PAHs in a one-step protocol using a triethy...

The energy transfer (EnT)-catalyzed ring opening and further decarboxylation of isoxazole-5(4H)-ones enables the in situ generation of strained 2H-azirines. Subsequent selective C(sp²)–C(sp³) bond cleavage of the azirine intermediate allows a formal [3 + 2] cycloaddition with a wide range of electrophiles, unlocking access to valuable pyrroline-typ...

Radical‐polar crossover (RPC) is a classic concept that bridges one‐ and two‐electron chemistry. It has been widely used in Cr‐catalyzed carbonyl addition reactions to clarify the formation of alkyl chromium(III) intermediate and subsequent carbonyl insertion. Herein, we proposed an orthogonal bonding model, the radical buffering scenario, for Cr‐c...

N-substituted phenothiazines are prominent and highly effective organic photoredox catalysts, particularly known for their strong reducing capabilities. Despite their wide utility, the closely related phenothiazine sulfoxides, which easily form upon oxidation, have been largely overlooked and have not been explored in the context of photocatalysis....

Radical‐polar crossover is a classic concept that bridges one‐ and two‐electron chemistry. It has been widely used in Cr‐catalyzed carbonyl addition reactions to clarify the formation of alkyl chromium(III) intermediate and subsequent carbonyl insertion. Herein, we proposed an orthogonal bonding model, the radical buffering scenario, for Cr‐catalyz...

So you've discovered a reaction. But how do you turn this new discovery into a fully-fledged program that maximises the potential of your novel transformation? Herein, we provide a student's checklist to serve as a helpful guide for synthesis development, allowing you to thoroughly investigate the chemistry in question while ensuring that no key as...

Ring scaffolds constitute important sub-structures in nature and across the chemical industries. However, their straight-forward introduction into a target molecule or cross-linkage between cyclic motifs of choice comprise major challenges for methodology development. Herein, the interconnection of two prominent representatives of the 2D and 3D cyc...

Herein we report a simple BF3-catalyzed cycloaddition of dihydropyridines with bicyclobutanes for the expedient synthesis of novel three-dimensional azacycle-fused bicyclo[2.1.1]hexane scaffolds. The reaction utilizes easily accessible starting materials and proceeds...

In this study, the solvent‐dependent divergent 1,2‐ and 1,3‐cyclization of bicyclo[1.1.0]butanes were achieved. This protocol straightforwardly led to a diverse range of oxa‐bicyclic heptanes, which may serve as lead bioisosteres in drug discovery, as well as highly functionalized cyclobutanes with exceptional diastereoselectivity. Mechanistic inve...

Bicyclo[1.1.0]butanes (BCBs) have recently garnered significant research interest as versatile precursors for synthesizing potential [n.1.1] bioisosteres and multi‐functionalized cyclobutanes in a straightforward and atom‐economical manner. Here, we report a solvent‐dependent divergent cyclization of BCBs that providecs highly diastereospecific dec...

The accelerated generation of reaction data through high-throughput experimentation and automation has the potential to boost organic synthesis. However, efforts to generate diverse reaction datasets or identify generally applicable reaction conditions are still hampered by limitations in reaction yield quantification. In this work, we present an a...

Despite the prominence of C−N bond forming cross‐coupling reactions as a strategy to assemble molecular fragments, aminative coupling approaches, in which two fragments are assembled directly at the heteroatom, represents a rarely exploited retrosynthetic strategy. Herein, we report the design, synthesis, and implementation of an anomeric amide rea...

Despite the prominence of C−N bond forming cross‐coupling reactions as a strategy to assemble molecular fragments, aminative coupling approaches, in which two fragments are assembled directly at the heteroatom, represents a rarely exploited retrosynthetic strategy. Herein, we report the design, synthesis, and implementation of an anomeric amide rea...

Replacing planar aromatic rings in drug molecules with C(sp³)-rich isosteric mimetics, such as bicyclo[n.1.1]alkanes, can significantly alter their physicochemical and pharmacokinetic properties, often leading to higher clinical success rates. However, unlike a benzene ring, the structurally rigid C(sp³)-rich isosteric mimetics of heteroaromatic ri...

Azoarene isomerization lies at the heart of numerous applications, from catalysis or energy storage to photopharmacology. While efficient switching between their E and Z isomers predominantly relies on UV light, a recent study by Klajn and co‐workers introduced visible light sensitization of E azoarenes and their subsequent isomerization as a tool...

Dynamic covalent polymer networks exhibit a cross‐linked structure like conventional thermosets and elastomers, although their topology can be reorganized through externally triggered bond exchange reactions. This characteristic enables a unique combination of repairability, recyclability and dimensional stability, crucial for a sustainable industr...

Organocatalysis has established itself as a third pillar of homogeneous catalysis, besides transition metal catalysis and biocatalysis, as its use for enantioselective reactions has gathered significant interest over the last decades. Concurrent to this development, machine learning (ML) has been increasingly applied in the chemical domain to effic...

The fluctuating reproducibility of scientific reports presents a well-recognised issue, frequently stemming from insufficient standardisation, transparency and a lack of information in scientific publications. Consequently, the incorporation of newly developed synthetic methods into practical applications often occurs at a slow rate. In recent year...

The targeted and selective replacement of a single atom in an aromatic system represents a powerful strategy for the rapid interconversion of molecular scaffolds. Herein, we report a pyridine-to-benzene transformation via nitrogen-to-carbon skeletal editing. This approach proceeds via a sequence of pyridine ring-opening, imine hydrolysis, olefinati...

Azoarene isomerization lies at the heart of numerous applications from catalysis or energy storage to photopharmacology. While efficient switching between their E and Z isomers predominantly relies on UV light, a recent study by Klajn and co‐workers introduced visible light sensitization of E azoarenes and subsequent isomerization as a tool coined...

Cholesterol is an important lipid playing a crucial role in mediating essential cellular processes as well as maintaining the basic structural integrity of biological membranes. Given its vast biological importance, there is an unabated need for sophisticated strategies to investigate cholesterol-mediated biological processes. Raman-tagged sterol a...

The accelerated generation of reaction data through high-throughput experimentation and automation has the potential to boost organic synthesis. However, efforts to generate diverse reaction datasets or identify generally applicable reaction con-ditions are still hampered by limitations in reaction yield quantification. In this work, we present a s...

Dynamic covalent polymer networks exhibit a cross-linked structure like conventional thermosets and elastomers, although their topology can be reorganized by thermoactivated bond exchange. This characteristic enables a unique combination of repairability, recyclability and dimensional stability, crucial for a sustainable industrial economy. We here...

Organocatalysis has established itself as a third pillar of homogeneous catalysis, besides transition metal catalysis and biocatalysis, as its use for enantioselective reactions has gathered significant interest over the last decades. Concurrent to this development, machine learning (ML) has been increasingly applied in the chemical domain to effic...

Synthesis of bicyclic scaffolds has emerged as an important research topic in modern drug development because they can serve as saturated bioisosters to enhance the physicochemical properties and metabolic profiles of drug candidates. Here we report a remarkably simple silver‐enabled strategy to access polysubstituted 3‐azabicyclo[3.1.1]heptanes in...

The available methods of chemical synthesis have arguably contributed to the prevalence of aromatic rings, such as benzene, toluene, xylene, or pyridine, in modern pharmaceuticals. Many such sp²-carbon-rich fragments are now easy to synthesize using high-quality cross-coupling reactions that click together an ever-expanding menu of commercially ava...

With over 10,000 new reaction protocols arising every year, only a handful of these procedures transition from academia to application. A major reason for this gap stems from the lack of comprehensive knowledge about a reaction’s scope, i.e., to which substrates the protocol can or cannot be applied. Even though chemists invest substantial effort t...

In the long-standing quest to synthesize fundamental building blocks with key functional group motifs, photochemistry in the recent past has comprehensively established its attractiveness. Amino alcohols are not only functionally diverse but are ubiquitous in the biologically active realm of compounds. We developed bench-stable bifunctional reagent...

The light-induced N=N double bond isomerization of azoarenes lies at the heart of numerous applications ranging from catalysis, energy storage, or drug release to optogenetics and photopharmacology. While efficient switching between their E and Z states has predominantly relied on direct UV light excitation, a recent study by Klajn and co-workers i...

Heteroaromatic rings play a prominent role in medicinal chemistry, featuring in numerous biologically relevant molecules. However, unlike benzene ring the saturated and structurally rigid bioisosteric mimetics of heteroaromatic rings are rarely known, mainly due to the inherent challenges associated with the stability and synthesis of heteroatom-su...

The varying quality of scientific reports is a well-recognized problem and often results from a lack of standardization and transparency in scientific publications. This situation ultimately leads to prominent complications such as reproducibility issues and the slow uptake of newly developed synthetic methods for pharmaceutical and agrochemical ap...

As the chemistry that surrounds the field of strained hydrocarbons, such as bicyclo[1.1.0]butane, continues to expand, it becomes increasingly advantageous to develop alternative reactivity modes that harness their unique properties to access new regions of chemical space. Herein, we report the use of photoredox catalysis to promote the single-elec...

Synthesis of bicyclic scaffolds has emerged as an important research topic in modern drug development because they can serve as saturated bioisosters to enhance the physicochemical properties and metabolic profiles of drug candidates. Here we report a remarkably simple silver‐enabled strategy to access polysubstituted 3‐azabicyclo[3.1.1]heptanes in...

Skeletal editing has received unprecedented attention as an emerging technology for the late-stage manipulation of molecular scaffolds. The direct achievement of functionalized carbon-atom insertion in aromatic rings is challenging. Despite ring-expanding carbon-atom insertion reactions, such as the Ciamician–Dennstedt re-arrangement, being perform...

Excited (triplet) states offer a myriad of attractive synthetic pathways, including cycloadditions, selective homolytic bond cleavages and strain-release chemistry, isomerizations, deracemizations, or the fusion with metal catalysis. Recent years have seen enormous advantages in enabling these reactivity modes through visible-light-mediated triplet...

The adsorption of N‐heterocyclic olefins (NHOs) on silicon is investigated in a combined scanning tunneling microscopy, X‐ray photoelectron spectroscopy, and density functional theory study. We find that both of the studied NHOs bind covalently, with ylidic character, to the silicon adatoms of the substrate and exhibit good thermal stability. The a...

The adsorption of N‐heterocyclic olefins (NHOs) on silicon is investigated in a combined scanning tunneling microscopy, X‐ray photoelectron spectroscopy, and density functional theory study. We find that both of the studied NHOs bind covalently, with ylidic character, to the silicon adatoms of the substrate and exhibit good thermal stability. The a...

Being an essential multifunctional platform and interface to the extracellular environment, the cell membrane constitutes a valuable target for the modification and manipulation of cells and cellular behavior, as well as for the implementation of artificial, new-to-nature functionality. While bacterial cell surface functionalization via expression...

The synthesis and properties of photoswitchable electron-rich phosphines containing N-heterocyclic imines equipped with a photochromic dithienylethene unit are reported. Heteronuclear NMR spectroscopy and UV/vis studies reveal that the imine substituents...

Surface modification of indium tin oxide (ITO) electrodes with organic molecules is known to tune their work function which results in higher charge carrier selectivity in corresponding organic electronic devices and hence influences the performance of organic solar cells. In recent years, N‐heterocyclic carbenes (NHCs) have also been proven to be...

N-Heterocyclic carbenes (NHCs) are established ligands for metal complexes and surfaces. Here we go beyond monomeric NHCs and report on the synthesis of NHC polymers on gold surfaces, consisting of ballbot-type repeating units bound to single Au adatoms. We designed, synthesized and deposited precursors containing different halogens on gold surface...

N-Heterocyclic carbene (NHC)-modified planar gold surfaces (NHC@Au) were found to be more susceptible toward wet chemical etching than undecorated surface areas. Site-selective decoration of NHCs on Au was achieved by microcontact printing (μCP) of the NHC precursors 1,3-bis(diisopropylphenyl)imidazol-3-ium hydrogen carbonate (IPr(H)[HCO3]) or 1,3-...

The highly enantioselective and complete hydrogenation of protected indoles and benzofurans has been developed, affording facile access to a range of chiral three-dimensional octahydroindoles and octahydrobenzofurans, which are prevalent in many bioactive molecules and organocatalysts. Remarkably, we are in control of the nature of the ruthenium N-...

(Hetero)aromatic compounds are vastly available and easy to functionalise building blocks in the chemical industry. Asymmetric arene hydrogenation enables direct access to complex three-dimensional scaffolds with (multiple) defined stereocentres in a single catalytic process and, by this, the rapid installation of molecular complexity. The potentia...

Multi-catalytic reaction modes have attracted widespread attention in synthetic chemistry. The merger of nickel catalysis with photoredox catalysis has offered a powerful platform for synthesis of molecules with attractive properties. Nonetheless, the conceptual development of nickel-catalysed, sensitized electron transfer is of pivotal relevance,...

Skeletal ring enlargement is gaining renewed interest in synthetic chemistry and has recently focused on insertion of one or two atoms. Strategies for heterocyclic expansion through small-ring insertion remain elusive, although they would lead to the efficient formation of bicyclic products. Here, we report a photoinduced dearomative ring enlargeme...

Laser desorption/ionization-mass spectrometry (LDI-MS) is introduced as a complementary technique for the analysis of interphases formed at electrode|electrolyte interfaces in lithium ion batteries (LIBs). An understanding of these interphases is crucial for designing interphase-forming electrolyte formulations and increasing battery lifetime. Espe...

Given the current global climate and health challenges, sustainability and cost-effectiveness are becoming unavoidable factors that must be considered in the development of new synthetic methodologies. In a recent publication, Kavthe et al. (R. D. Kavthe, K. S. Iyer, J. C. Caravez and B. H. Lipshutz, Chem. Sci., 2023, 14, 6399, https://doi.org/10.1...

Cholesterol is a sterol lipid found in all higher eukaryotic organisms. It is required to consolidate the basic structural integrity and dynamic principles of cellular membranes and participates in many essential cellular processes that range from signal transduction to membrane traffic and metabolism. Moreover, a growing number of clinically highl...

Dearomative photocycloadditions are valuable chemical transformations, serving as an efficient platform to create three-dimensional molecular complexity. However, the photolability of the original addition product especially within the context of ortho cycloadditions often causes undesired consecutive rearrangements, rendering these ortho cycloaddu...

Target occupancy is often insufficient to elicit biological activity, particularly for RNA, compounded by the longstanding challenges surrounding the molecular recognition of RNA structures by small molecules. Here we studied molecular recognition patterns between a natural-product-inspired small-molecule collection and three-dimensionally folded R...

The nongenetic modification of cell membranes with proteins is a straightforward way of cellular engineering. In these processes, it is important to specifically address the proteins to liquid-ordered (Lo) or liquid-disordered (Ld) domains as this can largely affect their biological functions. Herein, we report a cholesterol analogue (CHIM) with a...

A catalytic approach of synthesizing the cis-selective saturated carbo- and heterocyclic germanium compounds (3D framework) is reported via the hydrogenation of readily accessible aromatic germanes (2D framework). Among the numerous catalysts tested, Nishimura's catalyst (Rh2O3/PtO2·H2O) exhibited the best hydrogenation reactivity with an isolated...

Intermolecular carboamination of olefins offers a powerful platform for the rapid construction of structurally complex amines from abundant feedstocks. However, these reactions often require transition-metal catalysis, and are mainly limited to 1,2-carboamination. Herein, we report a novel radical relay 1,4-carboimination across two distinct olefin...

The Phosphatidylinositol 3-phosphate 5-kinase Type III PIKfyve is the main source for selectively generated phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), a known regulator of membrane protein trafficking. PI(3,5)P2 facilitates the cardiac KCNQ1/KCNE1 channel plasma membrane abundance and therewith increases the macroscopic current amplitude. F...

The emergence of modern photocatalysis, characterized by mildness and selectivity, has significantly spurred innovative late-stage C–H functionalization approaches that make use of low energy photons as a controllable energy source. Compared to traditional late-stage functionalization strategies, photocatalysis paves the way toward complementary an...

Sulfur(VI) fluoride exchange (SuFEx) gives rise to a plethora of high-valent sulfur linkages; however, the availability of (aliphatic) sulfonyl fluoride manifolds lag behind, owing to the limited sources of introducing the SO2F moiety via a classical two-electron approach. Recently, radical-based methodologies have emerged as a complementary strate...

Stereochemical editing has recently risen to prominence, allowing the direct editing of organic molecules with stereocenter(s) to adjust their relative stereochemistry at a late‐stage. Several seminal light‐driven stereochemical editing reactions such as deracemization and epimerization have been successively developed. Recently, Wendlandt and co‐w...

Silicon is the element of choice in semiconductor devices and a functionalization of silicon surfaces is highly desirable for electronic industries. N-Heterocyclic carbenes have been demonstrated to be promising modifiers...

A coordination-induced trigger for catalytic activity is proposed on an N-heterocyclic carbene (NHC)-decorated ceria catalyst incorporating Cr and Rh (ICy-r-Cr0.19Rh0.06CeOz). ICy-r-Cr0.19Rh0.06CeOz was prepared by grafting 1,3-dicyclohexylimidazol-2-ylidene (ICy) onto H2-reduced Cr0.19Rh0.06CeOz (r-Cr0.19Rh0.06CeOz) surfaces, which went on to exhi...

Vicinal diamines, especially unsymmetrical ones, are among the most common structural motifs in biologically active molecules, natural products and pharmaceuticals. While the catalytic diamination of carbon–carbon double bonds provides rapid access to diamines, these reactions are often limited to installation of undifferentiated amino functionalit...

Being the principal component of biological membranes lipids are essential building blocks of life. Given their huge biological importance, the investigation of lipids, their properties, interactions and metabolic pathways is of prime importance for the fundamental understanding of living cells and organisms as well as the emergence of diseases. Di...

Stereochemical editing has recently risen to prominence, allowing the direct editing of organic molecules with stereocenter(s) to adjust their relative stereochemistry at a late‐stage. Several seminal light‐driven stereochemical editing reactions such as deracemization and epimerization have been successively developed. Recently, Wendlandt and co‐w...

Radical addition reactions of olefins have emerged as an attractive tool for the rapid assembly of complex structures, and have plentiful applications in organic synthesis, however, such reactions are often limited to polymerization or 1,2-difunctionalization. Herein, we disclose an unprecedented radical relay 1,4-oxyimination of two electronically...

Herein, a Cr/Photoredox‐catalyzed general synthetic strategy to access α‐benzylic alcohols, isochromanones, oxy alcohols and thio alcohols is unveiled. Alkylation of aldehydes being a crucial C−C bond forming reaction, designing competent catalytic systems would render an attractive and decorated set of diverse alcohol motifs. Considering the chall...

Synthesis of bicyclic scaffolds has attracted growing interest because they are of high importance in modern pharmaceutical development. Here we report a strategy to access polysubstituted 2-oxabicyclo[2.1.1]hexanes in a single operation from readily accessible benzoylformate esters and bicyclo[1.1.0]butanes via visible-light-induced triplet energy...

Herein, a Cr/Photoredox‐catalyzed general synthetic strategy to access α‐benzylic alcohols, isochromanones, oxy alcohols and thio alcohols is unveiled. Alkylation of aldehydes being a crucial C–C bond forming reaction, designing competent catalytic systems would render an attractive and decorated set of diverse alcohol motifs. Considering the chall...

Photochemical dearomative cycloaddition has emerged as a useful strategy to rapidly generate molecular complexity. Within this context, stereo- and regiocontrolled intermolecular para-cycloadditions are rare. Herein, a method to achieve photochemical cycloaddition of quinolines and alkenes is shown. Emphasis is placed on generating sterically conge...

Tuning the properties of oxide surfaces through the adsorption of designed ligands is highly desirable for several applications, such as catalysis. N-Heterocyclic carbenes (NHCs) have been successfully employed as ligands for the modification of metallic surfaces. On the other hand, their potential as modifiers of ubiquitous oxide surfaces still ne...

Cationic amphiphiles have been reported to show broad antimicrobial activity. The potential for antimicrobial resistance to these molecules is low owing to their general cell membrane permeabilizing mode of action. However, their applications are often limited by toxicity resulting from their low selectivity for microbial cell membranes. Herein, we...

Natural product (E)-anethole was isomerized to (Z)-anethole in a photocatalytic reaction. For this purpose, a self-designed cheap photoreactor was constructed. Among 11 photosensitizers (organo and metal complex compounds), Ir(p-tBu-ppy)3 led to the highest conversion. Triplet energies of (E)- and (Z)-anethole were predicted theoretically by DFT ca...

Cycloaddition reactions─epitomized by the Diels-Alder reaction─offer an arguably unmatched springboard for achieving chemical complexity, often with excellent selectivity, in a modular single step. We report the synthesis of aza-acenaphthenes in a single step by an unprecedented formal peri-(3 + 2) cycloaddition of simple quinolines with alkynes. A...

Heterogeneous palladium catalysts modified by N-heterocyclic carbenes (NHCs) are shown to be highly effective toward the direct synthesis of hydrogen peroxide (H2O2), in the absence of the promoters which are typically required to enhance both activity and selectivity. Catalytic evaluation in a batch regime demonstrated that through careful selecti...

Vicinal diamines, especially unsymmetrical ones, are among the most common structural motifs in biologically active molecules, natural products, and pharmaceuticals. While the catalytic diamination of carbon–carbon double bonds provides rapid access to diamines, these reactions are often limited to installing undifferentiated amino functionalities...

A new class of saturated boron‐incorporated cyclic molecules has been synthesized employing an arene‐hydrogenation methodology. cis‐Selective hydrogenation of easily accessible, and biologically important molecules comprising benzoxaborole, benzoxaborinin, and benzoxaboripin derivatives is reported. Among the various catalysts tested, rhodium cycli...