Research highlights

Dynamic control of chirality and self-assembly of double-stranded helicates with light

Posted on 2017-02-24

Helicity switching in biological and artificial systems is a fundamental process that allows for the dynamic control of structures and their functions. In contrast to chemical approaches to responsive behaviour in helicates, the use of light as an external stimulus offers unique opportunities to invert the chirality of helical structures in a non-invasive manner with high spatiotemporal precision. Here, we report that unidirectional rotary motors with connecting oligobipyridyl ligands, which can dynamically change their chirality upon irradiation, assemble into metal helicates that are responsive to light. The motor function controls the self-assembly process as well as the helical chirality, allowing switching between oligomers and double-stranded helicates with distinct handedness. The unidirectionality of the light-induced motion governs the sequence of programmable steps, enabling the highly regulated self-assembly of fully responsive helical structures. This discovery paves the way for the future development of new chirality-dependent photoresponsive systems including smart materials, enantioselective catalysts and light-driven molecular machines.

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Depeng Zhao, Thomas van Leeuwen, Jinling Cheng & Ben L. Feringa, Nature Chemistry 9, 250–256 (2017) (DOI: 10.1038/nchem.2668)


Emerging Targets in Photopharmacology

Posted on 2016-07-13

The field of photopharmacology uses molecular photoswitches to establish control over the action of bioactive molecules. It aims to reduce systemic drug toxicity and the emergence of resistance, while achieving unprecedented precision in treatment. By using small molecules, photopharmacology provides a viable alternative to optogenetics. We present here a critical overview of the different pharmacological targets in various organs and a survey of organ systems in the human body that can be addressed in a non-invasive manner. We discuss the prospects for the selective delivery of light to these organs and the specific requirements for light-activatable drugs. We also aim to illustrate the druggability of medicinal targets with recent findings and emphasize where conceptually new approaches have to be explored to provide photopharmacology with future opportunities to bring “smart” molecular design ultimately to the realm of clinical use.

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Michael M. Lerch, Mickel J. Hansen, Gooitzen M. van Dam, Wiktor Szymanski and Ben L. Feringa, Angewandte Chemie International Edition, 2016, ASAP (DOI: 10.1002/anie.201601931) (DOI: 10.1002/anie.201601931)


A chemically powered unidirectional rotary molecular motor based on a palladium redox cycle

Posted on 2016-06-13

The conversion of chemical energy to drive directional motion at the molecular level allows biological systems, ranging from subcellular components to whole organisms, to perform a myriad of dynamic functions and respond to changes in the environment. Directional movement has been demonstrated in artificial molecular systems, but the fundamental motif of unidirectional rotary motion along a single-bond rotary axle induced by metal-catalysed transformation of chemical fuels has not been realized, and the challenge is to couple the metal-centred redox processes to stepwise changes in conformation to arrive at a full unidirectional rotary cycle. Here, we present the design of an organopalladium-based motor and the experimental demonstration of a 360° unidirectional rotary cycle using simple chemical fuels. Exploiting fundamental reactivity principles in organometallic chemistry enables control of directional rotation and offers the potential of harnessing the wealth of opportunities offered by transition-metal-based catalytic conversions to drive motion and dynamic functions.

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Beatrice S. L. Collins, Jos C. M. Kistemaker, Edwin Otten, Ben L. Feringa, Nature Chemistry (2016) doi:10.1038/nchem.2543 (DOI: 10.1038/nchem.2543)


Intramolecular transport of small-molecule cargo in a nanoscale device operated by light

Posted on 2016-05-16

An intramolecular cargo transport device, based on a light-driven molecular motor, is presented. Detailed UV-vis and 1H NMR studies demonstrate that the gripper attached to the upper half of the molecular motor is able to pick up an acetyl group from one side of the lower stator and, after a photochemical Z–E isomerization, drop it on the opposite side.

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Jiawen Chen, Sander J. Wezenberga, Ben L. Feringa, Chem. Commun., 2016,52, 6765-6768 (DOI: 10.1039/C6CC02382G)


Unraveling the Photoswitching Mechanism in Donor–Acceptor Stenhouse Adducts

Posted on 2016-05-11

Molecular photoswitches have opened up a myriad of opportunities in applications ranging from responsive materials and control of biological function to molecular logics. Here, we show that the photoswitching mechanism of donor–acceptor Stenhouse adducts (DASA), a recently reported class of photoswitches, proceeds by photoinduced Z–E isomerization, followed by a thermal, conrotatory 4π-electrocyclization. The photogenerated intermediate is manifested by a bathochromically shifted band in the visible absorption spectrum of the DASA. The identification of the role of this intermediate reveals a key step in the photoswitching mechanism that is essential to the rational design of switching properties via structural modification.

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Michael M. Lerch, Sander J. Wezenberg, Wiktor Szymanski, and Ben L. Feringa,, J. Am. Chem. Soc., 2016, Article ASAP (DOI: 10.1021/jacs.6b01722)


Amphiphilic Molecular Motors for Responsive Aggregation in Water

Posted on 2016-02-09

The novel concept of amphiphilic molecular motors that self-assemble into responsive supramolecular nanotubes in water is presented. The dynamic function of the molecular motor units inside the supramolecular assemblies was studied using UV–vis absorption spectroscopy and cryo-transmission electron microscopy (cryo-TEM) microscopy. Reorganization between distinct, well-defined nanotubes and vesicles can be reversibly induced by light, going through the rotation cycle of the motor, i.e. driven by alternate photochemical and thermal isomerization steps in the system. This is the first example in which a molecular rotary motor shows self-assembly in an aqueous medium with full retention of its functionality, paving the way to increasingly complex, highly dynamic artificial nanosystems in water.

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Derk Jan van Dijken, Jiawen Chen, Marc C. A. Stuart, Lili Hou, and Ben L. Feringa, J. Am. Chem. Soc., 2016, 138 (2), pp 660–669 (DOI: 10.1021/jacs.5b11318)


Dynamic Inversion of Stereoselective Phosphate Binding to a Bisurea Receptor Controlled by Light and Heat

Posted on 2015-01-19

A chiral bisurea anion receptor, derived from a first-generation molecular motor, can undergo photochemical and thermal isomerization operating as a reconfigurable system. The two possible cis configurations in the isomerization cycle are opposite in helicity, as is shown by CD spectroscopy. 1H NMR titrations demonstrate that the P and M helical cis isomers hold opposite enantioselectivity in the binding of binol phosphate, while anion complexation by the intermediate trans isomer is not selective. The difference in the binding affinity of the enantiomers was rationalized by DFT calculations, revealing very distinct binding modes. Thus, the enantiopreferred substrate binding in this receptor can be inverted in a dynamic fashion using light and heat.

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Matea Vlatković, Ben L. Feringa, Sander J. Wezenberg, Angew. Chem. Int. Ed. 2016, 55, 1001 (DOI: 10.1002/anie.201509479)


Visible-Light-Driven Photoisomerization and Increased Rotation Speed of a Molecular Motor Acting as a Ligand in a Ruthenium(II) Complex

Posted on 2015-09-30

Toward the development of visible-light-driven molecular rotary motors, an overcrowded alkene-based ligand and the corresponding ruthenium(II) complex is presented. In our design, a 4,5-diazafluorenyl coordination motif is directly integrated into the motor function. The photochemical and thermal isomerization behavior has been studied by UV/Vis and NMR spectroscopy. Upon coordination to a RuII bipyridine complex, the photoisomerization process can be driven by visible (λmax=450 nm) instead of UV light and furthermore, a large increase of the speed of rotation is noted. DFT calculations point to a contraction of the diazafluorenyl lower half upon metal-coordination resulting in reduced steric hindrance in the “fjord region” of the molecule. Consequently, it is shown that metal-ligand interactions can play an important role in the adjustment of both photophysical and thermodynamic properties of molecular motors.

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Sander J. Wezenberg, Kuang-Yen Chen, Ben L. Feringa, Angew. Chem. Int. Ed. 2015, 54, 11457 –11461 (DOI: 10.1002/anie.201505781)


Molekulare Motoren, Nobelpreisträger und ein holländischer Ritter

Posted on 2015-09-08

Professor Ben Feringa von der der Universität Groningen (Niederlande) ist der diesjährige Preisträger der Diels-Planck-Lecture. Der Preis wird jährlich durch die Mitglieder des Kieler Nano-Forschungsschwerpunktes (KINSIS) an führende Wissenschaftlerinnen und Wissenschaftler in den Bereichen Nano- und Oberflächenwissenschaften vergeben. Die Vortragsreihe ehrt die Begründer der Nanowissenschaften in Kiel, die Nobelpreisträger Max Planck und Otto Diels. In seinem Vortrag „The Art of Building Small: From Molecular Switches to Molecular Motors“ berichtete der Preisträger am Donnerstag, 3. September, im Audimax der Christian-Albrechts-Universität zu Kiel (CAU) über die bahnbrechenden Beiträge aus seiner Arbeitsgruppe auf dem Gebiet der molekularen Nanowissenschaften. Seine interdisziplinäre Forschung machtFeringa zu einem idealen Kandidaten für die Verleihung der Diels-Planck-Medaille, betonte CAU-Vizepräsidentin Professorin Karin Schwarz: „Auch Max Planck als Physiker und Otto Diels als Chemiker waren Pioniere in den Nanowissenschaften.“

„Ben Feringa ist einer der kreativsten und produktivsten Chemiker der Gegenwart. Mit über 900 Publikationen in den angesehensten Zeitschriften, zahlreichen Patenten und Büchern hat er wichtige Beiträge in vielen Bereichen der Chemie erbracht“, sagt Professor Rainer Herges vom Kieler Otto Diels-Institut für Organische Chemie in seiner Laudatio. Am bekanntesten sei Feringas Arbeitsgruppe für die Entwicklung des ersten mit Licht betriebenen molekularen Motors. „Damit hat er den entscheidenden Beitrag zur Entwicklung der molekularen Nanotechnologie in den 90er Jahren geliefert. Seine wissenschaftliche Pionierarbeit begründete einen neuen wichtigen Forschungszweig in den Nanowissenschaften“, erläutert Herges. Für die Entwicklung molekularer Schalter, des „Feringa-Motors“ und seiner Anwendungen wurde der Preisträger bereits mit zahlreichen internationalen Preisen geehrt und im Jahr 2008 von der Königin der Niederlande zum Ritter geschlagen.

Molekulare Motoren gibt es in der Natur zuhauf: Jede Zellteilung, jede Muskelbewegung und selbst Gehirnfunktionen sind nur möglich, wenn Moleküle gezielt von einem Ort im Körper an einen anderen transportiert werden. Durch die Nachbildung solcher „Motoren“ sind beispielsweise auch an- und abschaltbare Antibiotika möglich geworden, die nur an dem Ort der Krankheit wirken. Professor Feringa sieht viele gesellschaftliche Herausforderungen der Zukunft auch als Herausforderungen seiner Disziplin: „Nahrung, Medikamente, sauberes Wasser oder Energie könnten mit den richtigen Werkzeugen durch chemische Prozesse erzeugt werden.“ In seiner motivierenden Keynote sprach Feringa daher gezielt den wissenschaftlichen Nachwuchs an: „Haben Sie keine Angst, Neuland zu betreten. Überschreiten Sie Grenzen und versuchen Sie, Neues zu entwickeln – denn es gibt viel zu tun.“

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Palladium-Catalyzed C(sp3)–C(sp2) Cross-Coupling of (Trimethylsilyl)methyllithium with (Hetero)Aryl Halides

Posted on 2015-06-10

The palladium-catalyzed direct cross-coupling of a range of organic chlorides and bromides with the bifunctional C(sp3)-(trimethylsilyl)methyllithium reagent is reported. The use of Pd-PEPPSI-IPent as the catalyst allows for the preparation of structurally diverse and synthetically versatile benzyl- and allylsilanes in high yields under mild conditions (room temperature) with short reaction times.

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Heijnen, Dorus; Hornillos, Valentin; Corbet, Brian P; Giannerini, Massimo; Feringa, Ben L, Organic letters, 2015, 17 (9), 2262


Catalyst-controlled reverse selectivity in C–C bond formation: NHC-Cu-catalyzed α-selective allylic alkylation with organolithium reagents

Posted on 2015-06-10

An efficient and highly α-selective copper-catalyzed allylic alkylation of allylic halides with organolithium reagents is presented. The use of N-heterocyclic carbenes as ligands is key to reverse the common γ-selectivity of this transformation and gives rise to the corresponding linear products with high levels of regioselectivity.

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Pizzolato, Stefano F.; Giannerini, Massimo; Bos, Pieter H.; Fananas-Mastral, Martin ; Feringa, Ben L.


Direct catalytic cross-coupling of alkenyllithium compounds

Posted on 2015-03-10

A catalytic method for the direct cross-coupling of alkenyllithium reagents with aryl and alkenyl halides is described. The use of a catalyst comprising Pd2(dba)3/XPhos allows for the stereoselective preparation of a wide variety of substituted alkenes in high yields under mild conditions. In addition (1-ethoxyvinyl)lithium can be efficiently converted into substituted vinyl ethers which, after hydrolysis, give readily access to the corresponding methyl ketones in a one pot procedure.

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Valentín Hornillos, Massimo Giannerini, Carlos Vila, Martín Fañanás-Mastral and Ben L. Feringa, Chem. Sci., 2015,6, 1394-1398 (DOI: 10.1039/c4sc03117b)


Bacterial patterning controlled by light exposure

Posted on 2015-03-10

Patterning of multiple bacterial strains in one system is achieved by employing a single photo-activated antibiotic. Varying the light-exposure time results in zones with mixed and single populations.

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Willem A. Velema, Jan Pieter van der Berg, Wiktor Szymanski, Arnold J. M. Driessen and Ben L. Feringa, Org. Biomol. Chem., 2015,13, 1639-1642 (DOI: 10.1039/c4ob02483d)


Photo-controlled deactivation of immobilised lipase

Posted on 2014-09-02

Chem.Comm. 2014, DOI:10.1039/c4cc06087c

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Facile Assembly of Light-Driven Molecular Motors onto a Solid Surface

Posted on 2014-09-02

Chem.Comm. 2014, DOI:10.1039/c4cc04440a

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Photocaging of Carboxylic Acids: A Modular Approach

Posted on 6 MAY 2014

Mix and match: the multicomponent Passerini reaction is used for the preparation of photocaged carboxylic acids, both in dichloromethane and water. The choice of the aldehyde allows for tuning the deprotection wavelength and the preparation of orthogonally protected products. The isocyanide component may be used for immobilization on a solid support or introduction of either a reactive tag or a photosensitizer.

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W. Szymanski, W. A. Velema, B. L. Feringa


Supramolecular Chemistry on Graphene Field‐Effect Transistors

Posted on 5 March 2014

The electronic properties of large‐area graphene transistors (1 mm - 1 mm) prepared from commercially available graphene on silicon/silicon dioxide modified by self‐assembled bis‐urea‐terthiophene (T3) and bis‐urea‐nonane (C9) molecular wires are reported. Gate spectroscopy on molecularly modified graphene transistors show that the electronic interaction between the molecular wires and the graphene is weak compared to the effect of unwanted dopants.

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Xiaoyan Zhang, Everardus H. Huisman, Mallikarjuna Gurram, Wesley R. Browne, Bart J. van Wees, Ben L. Feringa, 2014, Small, in press (DOI: 10.1002/smll.201303098)


Autoamplification of Molecular Chirality through the Induction of Supramolecular Chirality

Posted on 24 February 2014

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D.J.van Dijken, J.M. Beierle, M.C.A. Stuart, W. Szymański, W.R. Browne, B.L. Feringa, 2014, Angew. Chem. Int. Ed., in press (DOI: 10.1002/anie.201311160)


Photopharmacology: beyond proof of principle

Posted on 7 February 2014

Pharmacotherapy is often severely hindered by issues related to poor drug selectivity, including side-effects, environmental toxicity and the emergence of resistance. Lack of selectivity is caused by the inability to control drug activity in time and space. Photopharmacology aims at solving these issues by incorporating photoswitchable groups into the molecular structure of bioactive compounds. These switching units allow for the use of light as an external control element for pharmacological activity, which can be delivered with very high spatiotemporal precision. This perspective presents the reader with the current state and outlook on photopharmacology. In particular, the principles behind photoregulation of bioactivity, the challenges of molecular design and the possible therapeutic scenarios are discussed.

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Willem A. Velema, Wiktor Szymanski, and Ben L. Feringa, J. Am. Chem. Soc. 2014 (DOI: 10.1021/ja413063e)


Light controlled formation of vesicles and supramolecular organogels by a cholesterol bearing amphiphilic molecular switch

Posted on 3 February 2014

A unique single molecule system has been designed that shows responsive self-assembly both in water and organic solvents. Light triggered reversible vesicle formation in aqueous solutions is reported. The cholesterol-bearing amphipihilic dithienyl ethene molecule behavior shows different behavior in organic media, where light controlled organogel formation is observed. The light triggered aggregating behavior of this molecule in both aqueous and non-aqueous media is described, opening new avenues in responsive soft materials.

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Jochem T. van Herpt, Jetsuda Areephong, Marc C. A. Stuart, Wesley R. Browne, Ben L. Feringa, Chem. Eur. J. 2014, 20 (6), 1737-1742 (DOI: 10.1002/chem.201302902)


Photochemical control of the generation of 1O2 by a photosensitizer using diarylethene switches

Posted on 30 Jan. 2014

Singlet oxygen (1O2), the first excited state of molecular oxygen, is highly reactive and can damage organic materials and biological tissues. One of the most important applications of singlet oxygen generation is in photodynamic therapy (PDT), which is used clinically to treat diseases through exposure of tissue to light. Reversible noninvasive control over the generation of singlet oxygen is now demonstrated in a bicomponent system comprising a diarylethene photo-chromic switch and a porphyrin photosensitized by selective irradiation at distinct wavelengths.

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Lili Hou, Xiaoyan Zhang, Thomas C. Pijper, Wesley R. Browne, Ben L. Feringa, J. Am. Chem. Soc. 2014, 136, 910 (DOI: 10.1021/ja4122473)


Hindered Aryllitihum Reagents as Highly Efficient Partners in Pd-Catalyzed Cross-Coupling Reactions: Synthesis of Tri- and Tetra-ortho-Substituted Biaryls Under Ambient Conditions

Posted on 7 November 2013

Elegant like a butterfly, sting like a lithium reagent: Highly hindered mono- and di-ortho substituted aryllithium reagents were coupled in the presence of PEPPSI-Ipent with hindered aryl bromides to form tri- and tetra-ortho-substituted biaryls. In virtue of the high reactivity of lithium reagents the reaction proceeds rapidly at room temperature, and represent one of the few methodologies to afford tetra-ortho-substituted biaryls under ambient conditions.

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Massimo Giannerini, Valentín Hornillos, Carlos Vila, Martín Fañanás-Mastral, Ben L. Feringa, Angew. Chem. Int. Ed. 2013,52,13329-13333 (DOI: 10.1002/anie.201306427)


Photo-Pharma: Optical control of antibiotic activity with light

Posted on 15 Sept. 2013

Build-up of antibiotics in the environment is turning into a major problem, leading to bacterial resistance. Novel molecular approaches that allow antibiotic activity to be limited both in space and time are therefore highly desirable. We have developed a responsive, broad-spectrum, antibacterial agent that can be temporarily activated by light, enabling antibiotic activity to be highly localized. This finding was published in Nature Chemistry in September 2013.

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Willem A. Velema, Jan Pieter van der Berg, Mickel J. Hansen, Wiktor Szymanski, Arnold J. M. Driessen & Ben L. Feringa, 2013, Nature Chemistry, 5, 924-928 (DOI: 10.1038/nchem.1750)


Tuning the Temperature Dependence for Switching in Dithienylethene Photochromic Switches

Posted on 29 July 2013

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Tibor Kudernac, Takao Kobayashi, Ayaka Uyama, Kingo Uchida, Shinichiro Nakamura, and Ben L. Feringa, J. Phys. Chem. A, 2013,117,8222-8229 (DOI: 10.1021/jp404924q)


Palladium-Catalyzed Selective Anti-Markovnikov Oxidation of Allylic Esters

Posted on 17 May 2013

An aldol alternative: The palladium(II)catalyzed anti-Markovnikov oxidation of allylic esters to aldehydes at room temperature provides a viable alternative to valuable cross aldol products. High regioselectivity towards the aldehyde product was achieved using the ester protecting group for the allylic alcohol. Rapid isomerization and the much higher rate of oxidation of the branched isomerresult in the same product forming from both linear and branched allylic esters.

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Jia Jia Dong, Martín Fañanás-Mastral, Paul L. Alsters, Wesley R. Browne, Ben L. Feringa, Angew. Chem. Int. Ed. 2013,52,5561-5565 (DOI: 10.1002/anie.201301809)


Bright Ion Channels and Lipid Bilayers

Posted on 18 April 2013

If we look at a simple organism such as a zebrafish under a microscope, we would see many cells working in harmony. If we zoomed in, we would observe each unit performing its own tasks in a special aqueous environment isolated from the other units by a lipid bilayer just about 5 nm thick. These confined units are social: they communicate with one another by sensing and responding to the chemical changes in their environment through receptors and ion channels. These channels control the highly specific and selective passage of ions from one side of the cell to the other and are embedded in lipid bilayers. The movement of ions through ion channels supports excitation and electrical signaling in the nervous system.
on channels have fascinated scientists not only because of their specificity and selectivity, but also for their functions, the serious consequences when they malfunction and the other potential applications of these molecules. Light offers a useful trigger to control and manipulate ion channels externally. With the many state-of-the-art optical technologies available, light offers a high degree of spatial and temporal control, millisecond precision and non-invasive intervention and does not change the chemical environment of the system of interest.
In this Account, we discuss research toward the dynamic control of lipid bilayer assembly and channel function, particularly the transport across the lipid bilayer-ion channel barrier of cells using light. We first summarize the manipulation of ion channel activity with light to modulate the channel's natural activity. Based on the type of photoswitch employed, we can achieve novel functionalities with these channels, and control neural activity. Then we discuss the recent developments in light-induced transport through lipid bilayers. We focus on three different approaches: the incorporation of photoswitchable copolymers into the lipids, the doping of the lipid bilayer with photosensitive amphiphiles and the preparation of the lipid bilayers solely from photoswitchable lipids.
These examples reflect the versatility of what we can achieve by manipulating biological systems with light, from triggering the permeability of a specific area of a lipid bilayer to controlling the behavior of a whole organism.

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Wiktor Szymanski, Duygu Yilmaz, ArmaĞan Koçer, and Ben L. Feringa, Acc. Chem.Res. 2013,46,2910-2923 (DOI: 10.1021/ar4000357)


Copper-Catalyzed Enantioselective Allyl-Allyl Cross-Coupling

Posted on 27 January 2013

A Cu(I)-phosphoramidite-based catalytic system that allows asymmetric allyl-allyl cross coupling with high enantioselectivity is reported. This transformation tolerates a large variety of functionalized substrates. The versatility of this new reaction is illustrated in the catalytic asymmetric synthesis of the Martinelline alkaloids chromene derivate-core.

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Valentín Hornillos, Manuel Pérez, Martín Fañanás-Mastral, and Ben L. Feringa, J. Am. Chem. Soc. 2013,135,2140-2143 (DOI: 10.1021/ja312487r)