: Late-stage functionalization (LSF) can introduce important chemical groups in the very last steps of the synthesis. LSF has the potential to speed up the preparation of novel chemical entities and ...diverse chemical libraries and have a major impact on drug discovery. Functional group tolerance and mild conditions allows access to new molecules not easily accessible by conventional approaches without the need for laborious
chemical synthesis.
: A historical overview of late-stage functionalization and its applicability to drug discovery is provided. Pioneering methodologies that laid the foundations for the field are briefly covered and archetypal examples of their application to drug discovery are discussed. Novel methodologies reported in the past few years mainly stemming from the recent renaissances of photoredox catalysis and radical chemistry are reviewed and their application to drug discovery considered.
: It is envisioned that late-stage functionalization will improve the efficiency and efficacy of drug discovery. There is evidence of the widespread uptake of LSF by the medicinal chemistry community and it is expected that the recent and continuing endeavors of many academic laboratories and pharmaceutical companies will soon have an impact on drug development.
The gold‐catalyzed CH annulation of anthranil derivatives with alkynes offers a facile, flexible, and atom‐economical one‐step route to unprotected 7‐acylindoles. An intermediate α‐imino gold ...carbene, generated by an intermolecular reaction, promotes ortho‐aryl CH functionalization to afford the target products. The transformation proceeds with a broad range of substrates under mild conditions. Moreover, the obtained functionalized indole products represent a versatile platform for the construction of diverse indolyl frameworks.
Good as gold: The gold‐catalyzed CH annulation of anthranil derivatives with alkynes offers a facile, flexible, and atom‐economical one‐step route to unprotected 7‐acylindoles. The reaction proceeds via an α‐imino gold carbene intermediate, which promotes ortho‐aryl CH functionalization to afford the product. The transformation proceeds with a broad range of substrates under mild conditions.
Over the past decade, the most significant, conceptual advances in the field of fluorination were enabled most prominently by organo‐ and transition‐metal catalysis. The most challenging ...transformation remains the formation of the parent CF bond, primarily as a consequence of the high hydration energy of fluoride, strong metal—fluorine bonds, and highly polarized bonds to fluorine. Most fluorination reactions still lack generality, predictability, and cost‐efficiency. Despite all current limitations, modern fluorination methods have made fluorinated molecules more readily available than ever before and have begun to have an impact on research areas that do not require large amounts of material, such as drug discovery and positron emission tomography. This Review gives a brief summary of conventional fluorination reactions, including those reactions that introduce fluorinated functional groups, and focuses on modern developments in the field.
Although known for more than 100 years, fluorination still remains a challenge today. Recent advances, to a large extent enabled by catalysis, have resulted in more efficient methods to introduce fluorine and fluorine‐containing functional groups into functionalized molecules. This Review focuses on new strategies for fluorination, with a brief introduction to conventional fluorination, so that the modern methods can be put into perspective.
Short and efficient syntheses of mono‐ and tris‐functionalized resorcin4arenes were developed. The co‐condensation of resorcinol and 2‐methylresorcinol was optimized, targeting for the ...trimethylresorcin4arene, easy to isolate. Complementary regiospecific conditions for the mono‐ and tris‐halogenation in almost quantitative yields are setting the stage for subsequent functionalizations: radicalic bromination leads to the trisbromomethyl compound, while the polar bromination and iodination via the mono‐lithiated species leads to the aryl bromide and iodide in excellent yields.
The reaction conditions for the co‐condensation of resorcinol and 2‐methylresorcinol were optimized, targeting for the trimethylresorcin4arene to be separated easily. Complementary regiospecific reaction conditions for the syntheses of mono‐ and tri‐halogenated resorcin4arenes in almost quantitative yields are setting the stage for subsequent functionalizations
In this feature article, the grafting of hyperbranched polymers to different substrates is reviewed. Both grafting onto macromolecules with different topologies (homogeneous grafting) and the ...resulting complex polymer architectures containing highly branched segments as well as their applications are discussed. In the second part grafting of hyperbranched polymers on surfaces, i.e., planar surfaces and spherical particles (heterogeneous grafting), with respect to specific applications, such as bio-repellent surfaces or soluble carbon nanotubes is described. In all cases, the one-step synthesis and the resulting highly branched topology of the hyperbranched building blocks is beneficial for the convenient introduction of a large number of functional groups to the substrates. These multifunctional hybrid materials open interesting options for applications, e.g., for highly functional nanoparticles or nanocomposites.
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Pre‐impregnated carbon fiber/epoxy resin (CF/epoxy prepreg) gained its popularity for significant stress applications, especially in the aerospace industry, owing to its excellent resistance and low ...specific mass. However, these CF/epoxy prepregs have a tendency to crack propagation. A solution for the prepregs fragility is the addition of carbon nanotubes (CNTs), especially those functionalized with amino groups, reinforcing the material due to its exceptional mechanical properties. In this work, the influence of the carbon chain length of two different amino‐functionalized CNTs from diverse backgrounds (commercial and laboratory growth CNTs) is studied. The nanofillers were added in CF/epoxy prepregs by dry spraying without solvent aid. CNTs' samples were characterized by X‐ray photoelectron spectroscopy, Raman spectroscopy, transmission electron microscopy, and thermogravimetric analysis (TGA), while the composites were analyzed by TGA, dynamic‐mechanical analysis, and field emission scanning electron microscopy. The various surface treatment occurred at different levels according to the CNTs background, and all samples exhibited a distinct behavior. These differences were also observed in the composites' thermomechanical performance: CNTs functionalized with larger carbon chain amine presented the best results, with an increase of almost 100% in the storage moduli (E'), confirming the efficiency of amino‐functionalized CNTs in the reinforcement of CF/epoxy prepregs.
Carbon fiber (CF) reinforced composites are widely used in many applications due to their excellent mechanical properties. However, the fiber/matrix interface is fragile, particularly in the interlaminar region where delamination can occur. Therefore, for optimizing the interface microstructure, we propose reinforcing CF/epoxy resin prepregs with amino‐functionalized carbon nanotubes (CNTs) to promote improved interaction between the composite's interlaminar layers, enhancing its mechanical properties and expanding the materials’ application.
The pyridine moiety is an important core structure for a variety of drugs, agrochemicals, catalysts, and functional materials. Direct functionalization of C-H bonds in pyridines is a straightforward ...approach to access valuable substituted pyridines. Compared to the direct ortho- and para-functionalization, meta-selective pyridine C-H functionalization is far more challenging due to the inherent electronic properties of the pyridine entity. This review summarizes currently available methods for pyridine meta-C-H functionalization using a directing group, non-directed metalation, and temporary dearomatization strategies. Recent advances in ligand control and temporary dearomatization are highlighted. We analyze the advantages as well as limitations of current techniques and hope to inspire further developments in this important area.
The direct α‐arylation of cyclic and acyclic ethers with heteroarenes has been accomplished through the design of a photoredox‐mediated CH functionalization pathway. Transiently generated α‐oxyalkyl ...radicals, produced from a variety of widely available ethers through hydrogen atom transfer (HAT), were coupled with a range of electron‐deficient heteroarenes in a Minisci‐type mechanism. This mild, visible‐light‐driven protocol allows direct access to medicinal pharmacophores of broad utility using feedstock substrates and a commercial photocatalyst.
Use visible light! The direct α‐arylation of cyclic and acyclic ethers with heteroarenes can be achieved at room temperature through a photoredox‐mediated CH functionalization pathway. This mild, visible‐light‐driven protocol allows direct access to medicinal pharmacophores of broad utility using feedstock substrates and a commercial photocatalyst. SET=single‐electron transfer.
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•Current trends in the alkoxylation chemistry of polyoxometalates.•Challenge: the controllable alkoxylation of polyoxometalates.•Synthetic strategies and structures of alkoxylated ...polyoxometalates are summarized.•Applications and future perspectives are reviewed.
Polyoxometalates (POMs), an exceptional family of coordination clusters consisting of Mo, W, V, etc. early transition metal ions in their highest oxidation states, have received significant attention over recent years due to their structural versatility and unique and diverse chemical and physical properties. The functionalization of POMs with organic ligands provides a novel strategy to precisely incorporate POMs with advanced functional organic moieties on their surfaces and enhance their compatibility in organic media. Among the various organically functionalized synthetic strategies for POM-based organic–inorganic hybrid materials, alkoxylation of POMs stands for one of the hottest topics during the past decades, since the diverse and tunable alkoxyl ligands are able to anchor on the surface of many POMs clusters, forming novel and flexible organically functionalized POM clusters, which can be further exploited as building blocks to design various functionalized POM-based hybrids with charming catalytic properties, and biomedicine, energy, or functional materials applications. In this review, recent advances in alkoxylation chemistry of POMs from synthetic strategies, structural overviews to their functional applications have been discussed.
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