A simple concept, namely exploiting the structural and stereochemical complexity of octahedral metal complexes, can have unexpected impact in different areas of chemical research, from medicinal ...chemistry and chemical biology to asymmetric catalysis and photoredox chemistry.
Visible light driven organic chemistry has sparked much excitement over the last several years. This review summarizes recent progress in combining visible light activation with asymmetric catalysis, ...processes that are either mediated by photoinduced electron or energy transfer. The tasks of photoactivation and asymmetric catalysis are typically accomplished by dual catalyst systems but several recent reports demonstrate that they can also be effectively executed by single catalysts. Beyond the discovery of novel asymmetric transformations under mild reaction conditions, this contemporary area of organic chemistry holds promise for the development of economical and environmentally friendly methods for the asymmetric synthesis of chiral compounds.
Recent advances in merging visible light activated photochemistry with asymmetric catalysis are summarized and discussed.
The tremendous challenge presented by the specific molecular recognition of single biomacromolecular targets within complex biological systems demands novel and creative design strategies. This ...Minireview discusses some conventional and unusual approaches for the design of target‐selective enzyme inhibitors with a focus on the underlying chemical scaffolds. These include complicated natural‐product‐like organic molecules, stable octahedral metal complexes, fullerenes, carboranes, polymetallic clusters, and even polymers. Thus the whole repertoire of organic, inorganic, and macromolecular chemistry can be applied to tackle the problem of target‐specific enzyme inhibition.
Creativity in demand: Enzyme inhibitor scaffolds ranging from typical small organic molecules to inorganic clusters and even to polymers demonstrate that the whole repertoire of organic, inorganic, and macromolecular chemistry can be used to meet the challenge of specific molecular recognition in complex biological systems.
In contrast to stereoselective organic chemistry, which has established sophisticated synthetic strategies to control the relative and absolute configuration at tetrahedral carbon atoms, the ...stereochemical control of octahedral coordination spheres is much less understood. This microreview reflects on the state of the art of asymmetric coordination chemistry of octahedral complexes within the historical context, including asymmetric coordination chemistry evolved by nature, the predetermination of metal‐centered chirality with tailored chiral ligands, chiral‐anion‐mediated asymmetric synthesis, chiral‐auxiliary‐mediated asymmetric coordination chemistry, and finally, very recent work on the catalytic asymmetric synthesis of an octahedral coordination complex. The stereocontrolled synthesis of octahedral metal complexes is an important problem of contemporary coordination chemistry and will ultimately provide the necessary synthetic tools to fully exploit the opportunities provided by the rich stereochemistry of octahedral coordination geometries.
This microreview provides an overview of the asymmetric coordination chemistry of octahedral metal complexes within the historical context, including examples from nature, the predetermination of metal‐centered chirality with tailored chiral ligands, chiral‐anion‐mediated and chiral‐auxiliary‐mediated asymmetric synthesis, and a recent example of the catalytic asymmetric synthesis of an octahedral coordination complex.
New methods for the stereocontrolled synthesis of octahedral metal complexes are needed in order to fully exploit the stereochemical richness of the octahedron in the fields of catalysis, materials ...sciences, and life sciences. Whereas a large body of work exists regarding the diastereoselective coordination chemistry with chiral ligands, such efforts are restricted to certain carefully designed chiral ligands which remain in the coordination sphere. The emerging strategy of chiral‐auxiliary‐mediated asymmetric synthesis holds promise to solve the problem of controlling relative and absolute configuration in octahedral metal complexes in a general fashion, thus hopefully in the future providing access to any desired optical active octahedral metal complex without the need for chiral separations. This short review will summarize reported examples of chiral auxiliaries applied to the asymmetric synthesis of octahedral metal complexes.
Complicated octahedron: New methods for the stereocontrolled synthesis of octahedral metal complexes are urgently needed in order to fully exploit the stereochemical richness of the octahedral coordination sphere. This short review discusses reported examples of chiral auxiliaries applied to the asymmetric synthesis of octahedral metal complexes (see scheme).
•Bioorthogonal activation of caged substrates by transition metal compounds.•Organopalladium-mediated modulation of protein activity within cells.•Palladium-nanoparticle-mediated activation of ...toxigenic prodrugs in the extracellular space.•Organoruthenium-mediated activation of a toxigenic prodrug within cells.•Organoiron-mediated activation of a fluorogenic compound within cells.
Photolabile protecting groups have been widely used for activation strategies of caged substrates within living cells. However, an alternative uncaging method in which, instead of light, chemical compounds are used as activators (chemical uncaging) is still in its infancy. The recent advances in bioorthogonal reactions mediated by transition metals have shown that bioorthogonal catalysts have the potential to yield such a chemical activator. By now we have seen transition metal compounds that activate caged enzymes, toxigenic prodrugs and other small molecules such as fluorophores within living human cells. In this review we will focus on metal catalysts based on palladium, ruthenium and iron and we will mainly discuss their biocompatibility and catalytic efficiency in uncaging reactions within biological environments.
A new class of chiral iron catalysts is introduced that contains exclusively achiral ligands with the overall chirality being the result of a stereogenic iron center. Specifically, iron(II) is ...cis-coordinated to two N-(2-pyridyl)-substituted N-heterocyclic carbene (PyNHC) ligands in a bidentate fashion in addition to two monodentate acetonitriles, and the dicationic complex is complemented by two hexafluorophosphate ions. Depending on the helical twist of the PyNHC ligands, the metal center adopts either a Λ or Δ absolute configuration. Importantly, the two PyNHC ligands are constitutionally and configurationally inert, while the two acetonitriles are labile and allow asymmetric transition metal catalysis. This is demonstrated with an enantioselective Cannizzaro reaction (96% yield, 88% ee) and an asymmetric Nazarov cyclization (89% yield, >20:1 dr, 83% ee).
Enantioenriched 1,4‐dicarbonyl compounds are versatile synthons in natural product and pharmaceutical drug synthesis. We herein report a mild pathway for the efficient enantioselective synthesis of ...these compounds directly from aldehydes through synergistic cooperation between a neutral eosin Y hydrogen atom transfer photocatalyst and a chiral rhodium Lewis acid catalyst. This method is distinguished by its operational simplicity, abundant feedstocks, atom economy, and ability to generate products in high yields (up to 99 %) and high enantioselectivity (up to 99 % ee).
It takes two: Enantioselective synthesis of 1,4‐dicarbonyl compounds directly from readily available aldehydes was accomplished with good yield and enantioselectivity through the synergistic combination of a neutral eosin Y hydrogen atom transfer photocatalyst and a bis‐cyclometalated rhodium catalyst.
Combining single electron transfer between a donor substrate and a catalyst‐activated acceptor substrate with a stereocontrolled radical–radical recombination enables the visible‐light‐driven ...catalytic enantio‐ and diastereoselective synthesis of 1,2‐amino alcohols from trifluoromethyl ketones and tertiary amines. With a chiral iridium complex acting as both a Lewis acid and a photoredox catalyst, enantioselectivities of up to 99 % ee were achieved. A quantum yield of <1 supports the proposed catalytic cycle in which at least one photon is needed for each asymmetric CC bond formation mediated by single electron transfer.
Combining single electron transfer between a donor substrate and a catalyst‐activated acceptor substrate with a stereocontrolled radical–radical recombination enables the visible‐light‐driven synthesis of 1,2‐amino alcohols from trifluoromethyl ketones and tertiary amines. With a chiral iridium complex acting as both a Lewis acid and a photoredox catalyst, enantioselectivities of up to 99 % ee were achieved.
Chemical (as opposed to light‐induced) activation of caged molecules is a rapidly advancing approach to trigger biological processes. We previously introduced the ruthenium‐catalyzed release of ...allyloxycarbonyl (alloc)‐protected amines in human cells. A restriction of this and all other methods is the limited lifetime of the catalyst, thus hampering meaningful applications. In this study, we addressed this problem with the development of a new generation of ruthenium complexes for the uncaging of alloc‐protected amines with superior catalytic activity. Under biologically relevant conditions, we achieved a turnover number >300, a reaction rate of 580 m−1 s−1, and we observed high activity in blood serum. Furthermore, alloc‐protected doxorubicin, as an anticancer prodrug, could be activated in human cell culture and induced apoptosis with a single low dose (1 μm) of the new catalyst.
Addressing the challenge of catalytic uncaging: A new generation of ruthenium complexes for the uncaging of alloc‐protected amines with superior catalytic activity under biorelevant conditions is reported. It was applied to the catalytic uncaging of the allyloxycarbonyl‐protected anticancer drug doxorubicin.
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