26 publications

26. Diverse Visible-Light-Promoted Functionalizations of Benzotriazoles Inspired by Mechanism-Based Luminescence Screening

M. Teders, A. Gómez-Suárez, L. Pitzer, M. N. Hopkinson, F. Glorius*

Angewandte Chemie International Edition | 2017

Angew. Chem. Int. Ed. 2017, 56, 902-906; Angew. Chem. 2017, 129, 921-925

Full Text (English)Full Text (Deutsch)

Drei neuartige, durch sichtbares Licht vermittelte Funktionalisierungen von Benzotriazolen als Quencher-Substratklasse, entdeckt mithilfe einer mechanismusbasierten Screening-Methode, wurden entwickelt. Mit dieser Synthesestrategie wurden unter milden Bedingungen ortho-thiolierte, borylierte und alkylierte N-Arylbenzamide erhalten. Die Verträglichkeit der Borylierungsreaktion mit funktionellen Gruppen wurde durch die erste Anwendung eines additivbasierten Robustheits-Screens einer photokatalytischen Transformation untersucht. Allen Funktionalisierungen liegen photokatalytisch initiierte Kettenmechanismen zugrunde, wie durch die Bestimmung der Reaktionsquantenausbeute und durch Stern-Volmer-Analysen ermittelt werden konnte.

Three new visible-light-promoted functionalizations of benzotriazole substrates were discovered using a mechanism-based screening method. ortho-Thiolated, borylated, and alkylated N-arylbenzamide products were obtained under mild reaction conditions in a new denitrogenative synthetic approach to functionalized aniline derivatives. The functional group tolerance of the borylation reaction was further analyzed in the first application of an additive-based robustness screen in a photocatalytic transformation. All the functionalizations proceed via photocatalytically initiated chain mechanisms as indicated by determination of the reaction quantum yields and Stern–Volmer analyses.

25. Merging Visible Light Photoredox and Gold Catalysis

M. N. Hopkinson,* A. Tlahuext-Aca, F. Glorius*

Accounts of Chemical Research | 2016

Acc. Chem. Res. 2016, 49, 2261-2272

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Since the beginning of this century, π-Lewis acidic gold complexes have become the catalysts of choice for a wide range of organic reactions, especially those involving nucleophilic addition to carbon–carbon multiple bonds. For the most part, however, the gold catalyst does not change oxidation state during the course of these processes and two-electron redox cycles of the kind implicated in cross-coupling chemistry are not easily accessible. In order to address this limitation and expand the scope of gold catalysis beyond conventional hydrofunctionalization, extensive efforts have been made to develop new oxidative reactions using strong external oxidants capable of overcoming the high potential of the AuI/AuIII redox couple. However, these processes typically require superstoichiometric amounts of the oxidant and proceed under relatively harsh conditions. Moreover, to date, gold-catalyzed oxidative coupling reactions have remained somewhat limited in scope because, for many systems, the desired cross-coupling does not favorably compete with homodimerization or conventional hydrofunctionalization. In 2013, we disclosed a new concept for gold-catalyzed coupling reactions that, rather than involving external oxidants, employs aryl radicals that act as both the oxidant and the coupling partner in overall redox-neutral transformations. For this, we developed a dual catalytic system combining homogeneous gold catalysis with the emerging field of visible light photoredox catalysis. Using aryldiazonium salts, which are known to act as sources of aryl radicals upon activation with reducing photocatalysts, we could achieve intramolecular oxy- and aminoarylations of alkenes upon irradiating the reaction mixtures with visible light. Further studies on this transformation, in which nucleophilic addition onto a gold-activated alkene is followed by C(sp3)–C(sp2) bond formation, expanded the scope of the process to intermolecular, three-component oxyarylation, while inexpensive organic dyes and user-friendly diaryliodonium salts could be employed as alternative photocatalysts and aryl radical sources, respectively. The potential of dual gold/photoredox catalysis was quickly realized by several research groups and a range of diverse new coupling reactions involving nucleophilic addition to π-systems and even P–H and C(sp)–H functionalization have been developed. In addition to the ambient reaction conditions and the simple setup using household light sources or even sunlight, a key advantage of dual gold/photoredox catalysis results from the simultaneous oxidation of gold(I) and coordination of the coupling partner, which results in high levels of selectivity for the cross-coupled products over homodimers. Furthermore, when gold complexes that are not catalytically active prior to oxidation by the aryl radical are employed, background reactions not involving coupling can be suppressed. Notably, this feature has allowed for the successful use of allenes and alkynes, for which conventional hydrofunctionalization pathways are highly favored, opening the door to new transformations involving the most common substrate classes for gold catalysis. In this Account, we provide an overview of dual gold/photoredox catalysis and highlight the potential of this concept to greatly expand the scope of homogeneous gold catalysis and enable the efficient construction of complex organic molecules. Moreover, recent studies on the visible light-promoted synthesis of novel gold(III) complexes suggest that photoredox activation could yet find further applications in gold chemistry beyond coupling.

24. Oxidative Addition to Gold(I) by Photoredox Catalysis: Straightforward Access to Diverse (C,N)-Cyclometalated Gold(III) Complexes

A. Tlahuext-Aca, M. N. Hopkinson, C. G. Daniliuc, F. Glorius*

Chemistry - A European Journal (Very Important Paper) | 2016

Chem. Eur. J. 2016, 22, 11587-11592

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Herein, we report the oxidative addition of aryldiazonium salts to ligand-supported gold(I) complexes under visible light photoredox conditions. This method provides experimental evidence for the involvement of such a process in dual gold/photoredox-catalyzed reactions and delivers well-defined (C,N)-cyclometalated gold(III) species. The remarkably mild reaction conditions and the ability to widely vary the ancillary ligand make this method a potentially powerful synthetic tool to access diverse gold(III) complexes for systematic studies into their properties and reactivity. Initial studies show that these species can undergo chloride abstraction to afford Lewis acidic dicationic gold(III) species.

23. Mild Metal-Catalyzed C–H Activation: Examples and Concepts

T. Gensch, M. N. Hopkinson, F. Glorius,* J. Wencel-Delord*

Chemical Society Reviews | 2016

Chem. Soc. Rev. 2016, 45, 2900-2936

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Organic reactions that involve the direct functionalization of non-activated C–H bonds represent an attractive class of transformations which maximize atom- and step-economy, and simplify chemical synthesis. Due to the high stability of C–H bonds, these processes, however, have most often required harsh reaction conditions, which has drastically limited their use as tools for the synthesis of complex organic molecules. Following the increased understanding of mechanistic aspects of C–H activation gained over recent years, great strides have been taken to design and develop new protocols that proceed efficiently under mild conditions and duly benefit from improved functional group tolerance and selectivity. In this review, we present the current state of the art in this field and detail C–H activation transformations reported since 2011 that proceed either at or below ambient temperature, in the absence of strongly acidic or basic additives or without strong oxidants. Furthermore, by identifying and discussing the major strategies that have led to these improvements, we hope that this review will serve as a useful conceptual overview and inspire the next generation of mild C–H transformations.

22. Accelerated Discovery in Photocatalysis using a Mechanism-based Screening Method

M. N. Hopkinson, A. Gómez-Suárez, M. Teders, B. Sahoo, F. Glorius*

Angewandte Chemie International Edition | 2016

Angew. Chem. Int. Ed. 2016, 55, 4361-4366; Angew. Chem. 2016, 128, 4434-4439

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Ein konzeptionell neuartiger mechanismusbasierter Screeningansatz zur schnellen Entdeckung photokatalytischer Reaktionen wird beschrieben. Im Unterschied zu herkömmlichen Screeningmethoden, in denen die gesamte Reaktion betrachtet wird, wird bei diesem Ansatz nur ein einzelner mechanistischer Schritt einer katalytischen Reaktion analysiert. Durch Verwendung von Lumineszenzspektroskopie zur Identifizierung des Quenching-Schlüsselschritts in photokatalytischen Reaktionen wurden in einem initialen Screening von 100 Komponenten zwei vielversprechende Substratklassen identifiziert. Ein zweites, fokussierteres Screening lieferte mechanistische Einblicke, die zur Entwicklung von Proof-of-Concept-Reaktionen verwendet wurden. Zusammenfassend erleichtert diese schnelle und intuitive Herangehensweise die Entdeckung und Entwicklung neuer photokatalytischer Reaktionen.

Herein, we report a conceptually novel mechanism-based screening approach to accelerate discovery in photocatalysis. In contrast to most screening methods, which consider reactions as discrete entities, this approach instead focuses on a single constituent mechanistic step of a catalytic reaction. Using luminescence spectroscopy to investigate the key quenching step in photocatalytic reactions, an initial screen of 100 compounds led to the discovery of two promising substrate classes. Moreover, a second, more focused screen provided mechanistic insights useful in developing proof-of-concept reactions. Overall, this fast and straightforward approach both facilitated the discovery and aided the development of new light-promoted reactions and suggests that mechanism-based screening strategies could become useful tools in the hunt for new reactivity.

21. Alkyne Difunctionalization by Dual Gold/Photoredox Catalysis

A. Tlahuext-Aca, M. N. Hopkinson,† R. A. Garza-Sanchez,† F. Glorius*

Chemistry - A European Journal | 2016

Chem. Eur. J. 2016, 22, 5909-5913

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Highly selective tandem nucleophilic addition/cross-coupling reactions of alkynes have been developed using visible-light-promoted dual gold/photoredox catalysis. The simultaneous oxidation of AuI and coordination of the coupling partner by photo-generated aryl radicals, and the use of catalytically inactive gold precatalysts allows for high levels of selectivity for the cross-coupled products without competing hydrofunctionalization or homocoupling. As demonstrated in representative arylative Meyer–Schuster and hydration reactions, this work expands the scope of dual gold/photoredox catalysis to the largest class of substrates for gold catalysts and benefits from the mild and environmentally attractive nature of visible-light activation.

20. Visible Light-Promoted Trifluoromethylthiolation of Styrenes via Dual Photoredox/Halide Catalysis

R. Honeker,† R. A. Garza-Sanchez,† M. N. Hopkinson,* F. Glorius*

Chemistry - A European Journal (Hot Paper) | 2016

Chem. Eur. J. 2016, 22, 4395-4399

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Herein, we report a new visible-light-promoted strategy to access radical trifluoromethylthiolation reactions by combining halide and photoredox catalysis. This approach allows for the synthesis of vinyl–SCF3 compounds of relevance in pharmaceutical chemistry directly from alkenes under mild conditions with irradiation from household light sources. Furthermore, alkyl–SCF3-containing cyclic ketone and oxindole derivatives can be accessed by radical-polar crossover semi-pinacol and cyclization processes. Inexpensive halide salts play a crucial role in activating the trifluoromethylthiolating reagent towards photoredox catalysis and aid the formation of the SCF3 radical.

19. Dual Gold/Photoredox-Catalyzed C(sp)−H Arylation of Terminal Alkynes with Diazonium Salts

A. Tlahuext-Aca,† M. N. Hopkinson,† B. Sahoo, F. Glorius*

Chemical Science | 2015

Chem. Sci. 2015, 7, 89-93

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The arylation of alkyl and aromatic terminal alkynes by a dual gold/photoredox catalytic system is described. Using aryldiazonium salts as readily available aryl sources, a range of diversely-functionalized arylalkynes could be synthesized under mild, base-free reaction conditions using visible light from simple household sources or even sunlight. This process, which exhibits a broad scope and functional group tolerance, expands the range of transformations amenable to dual gold/photoredox catalysis to those involving C–H bond functionalization and demonstrates the potential of this concept to access AuI/AuIII redox chemistry under mild, redox-neutral conditions.

18. External-Photocatalyst-Free Visible-Light-Mediated Synthesis of Indolizines

B. Sahoo,† M. N. Hopkinson,† F. Glorius*

Angewandte Chemie International Edition | 2015

Angew. Chem. Int. Ed. 2015, 54, 15545-15549; Angew. Chem. 2015, 127, 15766-15770

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Eine durch sichtbares Licht vermittelte Synthese von wertvollen, polycyclischen Indolizin-Heterocyclen aus leicht zugänglichen bromierten Pyridinen und Enolcarbamaten wurde entwickelt. Dieser Prozess, welcher bei Raumtemperatur unter Bestrahlung mit sichtbarem Licht stattfindet, läuft auch ohne die Zugabe eines externen Photokatalysators ab. Mechanistische Experimente deuten darauf hin, dass die Indolizinprodukte ihre eigene Bildung beschleunigen können. Zudem sind sie in der Lage, andere durch sichtbares Licht vermittelte Reaktionen zu beschleunigen.

A visible-light-mediated synthesis of valuable polycyclic indolizine heterocycles from easily accessed brominated pyridine and enol carbamate derivatives has been developed. This process, which operates at room temperature under irradiation from readily available light sources, does not require the addition of an external photocatalyst. Instead, an investigation into the reaction mechanism indicates that the indolizine products themselves may be in some way involved in mediating and accelerating their own formation. Preliminary studies also show that these simple heterocyclic compounds may be capable of facilitating other visible-light-mediated transformations.

17. Dual Photoredox and Gold Catalysis: Intermolecular Multicomponent Oxyarylation of Alkenes

M. N. Hopkinson, B. Sahoo, F. Glorius*

Advanced Synthesis and Catalysis | 2014

Adv. Synth. Catal. 2014, 356, 2794-2800

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Intermolecular three-component oxyarylation reactions of simple alkenes have been developed using a dual gold and photoredox catalytic system. Inexpensive organic dyes could be employed as the photocatalyst using aryldiazonium salts, while the combination of gold and iridium catalysts allowed for diaryliodonium compounds to be employed as the source of the arene coupling partner. In both cases, α-arylated ether products were generated under remarkably mild conditions using readily accessible visible light sources.

16. An Overview of N-Heterocyclic Carbenes

M. N. Hopkinson, C. Richter, M. Schedler, F. Glorius*

Nature | 2014

Nature 2014, 510, 485-496

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The successful isolation and characterization of an N-heterocyclic carbene in 1991 opened up a new class of organic compounds for investigation. From these beginnings as academic curiosities, N-heterocyclic carbenes today rank among the most powerful tools in organic chemistry, with numerous applications in commercially important processes. Here we provide a concise overview of N-heterocyclic carbenes in modern chemistry, summarizing their general properties and uses and highlighting how these features are being exploited in a selection of pioneering recent studies.

15. Using Rh(III)-Catalyzed C−H Activation as a Tool for the Selective Functionalization of Ketone-Containing Molecules

M. Boultadakis-Arapinis, M. N. Hopkinson, F. Glorius*

Organic Letters | 2014

Org. Lett. 2014, 16, 1630-1633

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Due to the strong potential of C–H activation in many areas of organic chemistry, the use of a pre-existing carbonyl group for the installation of a directing group to enable selective and predictable α-alkenylation with activated olefins as coupling partners is described. This Heck-type reaction would then lead either to β,γ-unsaturated ketones or to variously substituted 1,4-butadienes depending on the conditions used for the cleavage of the directing group.

14. Dual Catalysis sees the Light: Combining Photoredox with Organo-, Acid and Transition Metal Catalysis

M. N. Hopkinson,† B. Sahoo,† J.-L. Li, F. Glorius*

Chemistry - A European Journal | 2013

Chem. Eur. J. 2014, 20, 3874-3886

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The photoredox activation of organic substrates with visible light is a powerful methodology that generates reactive radical species under very mild conditions. When combined with another catalytic process in a dual catalytic system, novel, visible-light-promoted transformations have been realized that do not proceed using either catalyst in isolation. In this minireview, the state of the art in organic reactions mediated by dual catalytic systems merging photoredox activation with organo-, acid or metal catalysis is discussed.

13. Combining Gold and Photoredox Catalysis: Visible Light-Mediated Oxy- and Aminoarylation of Alkenes

B. Sahoo, M. N. Hopkinson, F. Glorius*

Journal of the American Chemical Society | 2013

J. Am. Chem. Soc. 2013, 135, 5505-5508

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A room-temperature intramolecular oxy- and aminoarylation of alkenes with aryldiazonium salts has been developed using a novel gold and photoredox dual-catalytic system. The compatibility of these two catalytic modes has been established for the first time and demonstrates the potential of this system as a method to expand the scope of nucleophilic addition reactions to carbon–carbon multiple bonds.

12. Beyond Directing Groups: Transition Metal-Catalyzed C–H Activation of Simple Arenes

N. Kuhl, M. N. Hopkinson, J. Wencel-Delord, F. Glorius*

Angewandte Chemie International Edition | 2012

Angew. Chem. Int. Ed. 2012, 51, 10236-10254; Angew. Chem. 2012, 124, 10382-10401

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Der Einsatz von koordinierenden Gruppen als dirigierende Gruppen ist eine zuverlässige Methode zur Kontrolle von Reaktivität und Selektivität bei der Aktivierung von Aryl-C-H-Bindungen. Im Hinblick auf die Anwendbarkeit von C-H-Aktivierungen in der Synthese besteht derzeit ein großes Interesse daran, Reaktionen zu entwickeln, in denen völlig auf dirigierende Gruppen verzichtet werden kann und somit die Funktionalisierung einfacher Benzolderivate möglich wird. Dieser Ansatz erfordert jedoch neue Strategien zur Reaktivitäts- und Selektivitätskontrolle. In diesem Kurzaufsatz werden aktuelle Fortschritte in dem noch jungen Gebiet der nicht-chelatvermittelten C-H-Aktivierung diskutiert, wobei einige inspirierende Beispiele zur Reaktivitäts- und Selektivitätsinduktion hervorgehoben werden.

The use of coordinating moieties as directing groups for the functionalization of aromatic C-H bonds has become an established tool to enhance reactivity and induce regioselectivity. Nevertheless, with regard to the synthetic applicability of C-H activation, there is a growing interest in transformations in which the directing group can be fully abandoned, thus allowing the direct functionalization of simple benzene derivatives. However, this approach requires the disclosure of new strategies to achieve reactivity and to control selectivity. In this review, recent advances in the emerging field of non-chelate-assisted C-H activation are discussed, highlighting some of the most intriguing and inspiring examples of induction of reactivity and selectivity.

11. Selective Rh(III)-Catalyzed Cross-Dehydrogenative Coupling of Furan and Thiophene Derivatives

N. Kuhl, M. N. Hopkinson, F. Glorius*

Angewandte Chemie International Edition | 2012

Angew. Chem. Int. Ed. 2012, 51, 8230-8234; Angew. Chem. 2012, 124, 8354-8358

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Eine heiße Verbindung: Eine Rhodium(III)-katalysierte gekreuzte dehydrierende Kupplung (CDC) von Furan- und Thiophenderivaten wird vorgestellt, die wertvolle 2,2′-Biheteroaryle in guten Ausbeuten und Selektivitäten liefert. Die Verwendung von Pyrrolen und Indolen als Kupplungspartner in dieser Reaktion ist ebenfalls möglich und führt zu den entsprechenden C3-arylierten Produkten.

A hot couple: An unprecedented rhodium(III)-catalyzed cross-dehydrogenative coupling (CDC) of various furan and thiophene derivatives leads to valuable 2,2′-bi(heteroaryl) products in good yields and selectivities (see scheme). In addition, pyrroles and indoles can also be used as coupling partners, giving C3-arylated products.

10. Metal-Free Oxidative Fluorination of Phenols with [18F]Fluoride

Z. Gao, Y. H. Lim, M. Tredwell, L. Li, S. Verhoog, M. Hopkinson, W. Kaluza, T. L. Collier, J. Passchier, M. Huiban, V. Gouverneur*

Angewandte Chemie International Edition | 2012

Angew. Chem. Int. Ed. 2012, 51, 6733-6737

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Die radiochemische Synthese von [18F]4-Fluorphenolen basiert auf einer Phenol-Umpolung unter oxidativen Bedingungen und der direkten nucleophilen Fluorierung mit [18F]Fluorid (siehe Schema, TBAF=Tetra-n-butylammoniumfluorid, TFA=Trifluoressigsäure). Einfach zugängliche O-ungeschützte 4-tert-Butylphenole dienen als Vorstufen in diesem Eintopf-Protokoll. Die Reaktion ist in 30 min bei Raumtemperatur abgeschlossen und kann mit Standard- und Mikrofluidiktechniken durchgeführt werden.

The radiochemical synthesis of [18F]4-fluorophenols is based on phenol umpolung under oxidative conditions and direct nucleophilic fluorination with [18F]fluoride (see scheme, TBAF=tetra-n-butylammonium fluoride, TFA=trifluoroacetic acid). Readily available O-unprotected 4-tert-butyl phenols are used as precursors in this one-pot protocol. The reaction is completed in less than 30 minutes at room temperature and can be performed using standard or microfluidic technology.

9. Gold-Catalyzed Coupling Reactions

M. N. Hopkinson, V. Gouverneur

Thieme: Stuttgart: Science of Synthesis Knowledge Updates | 2011

Science of Synthesis Knowledge Updates; Thieme: Stuttgart, (2011), Vol. 2011/2, Section 3.6.13, p101

This chapter covers homo- and cross-coupling reactions mediated by gold complexes under homogeneous conditions. In the first two sections, coupling reactions mediated by stoichiometric gold(III) complexes and catalytic cross-coupling reactions involving oxidative addition to gold(I) are presented. This is followed in the subsequent two sections by a discussion of recently developed gold-catalyzed homo- and cross-coupling processes using external oxidants.

8. AuI/AuIII Catalysis: An Alternative Approach for C−C Oxidative Coupling

M. N. Hopkinson,* A. D. Gee, V. Gouverneur*

Chemistry - A European Journal | 2011

Chem. Eur. J. 2011, 17, 8248-8262

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When reacted in the presence of external oxidants, gold complexes are capable of catalyzing oxidative homo- and cross-coupling reactions involving the formation of new C-C bonds. Over the last few years, several cascade processes have been reported in which coupling is preceded by a gold-mediated aryl C-H functionalization or nucleophilic addition. These reactions combine the unique reactivity of gold with oxidative coupling, enabling the construction of C-C bonds between coupling partners that are not easily accessed using alternative catalysts. In this Concept paper, the development of gold-catalyzed oxidative coupling reactions is discussed focusing on C-C bond-forming reactions of broad synthetic appeal.

7. Palladium-Catalyzed Allylic Fluorination

C. Hollingworth, A. Hazari, M. N. Hopkinson, M. Tredwell, E. Benedetto, M. Huiban, A. D. Gee, J. M. Brown,* V. Gouverneur*

Angewandte Chemie International Edition (Hot Paper) | 2011

Angew. Chem. Int. Ed. 2011, 50, 2613-2617

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Schnell und mild: Die Titelreaktion, die eine Fülle von Allylfluoriden zugänglich macht, beruht auf dem Einsatz der p-Nitrobenzoat-Abgangsgruppe (siehe Schema; TBAF=Tetra-n-butylammoniumfluorid, THF=Tetrahydrofuran, dba=Dibenzylidenaceton). Das katalytische metallorganische Fluorierungsverfahren eignet sich für radioaktive Markierungen mit 18F.

Mild and rapid: The title reaction is presented and its applicability to 18F radiolabeling is demonstrated (see scheme; TBAF=tetra-n-butylammonium fluoride, THF=tetrahydrofuran, dba=dibenzylideneacetone). The use of p-nitrobenzoate as the leaving group is significant to the success of this catalytic organometallic fluorination process. A range of allylic fluorides were synthesized by this method.

6. Convergent 18F Radiosynthesis: A New Dimension for Radiolabelling

L. Li, M. N. Hopkinson, R. Leuma Yona, R. Bejot, A. D. Gee, V. Gouverneur*

Chemical Science | 2011

Chem. Sci. 2011, 2, 123-131

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The availability of radiolabelled probes is important for in vivo studies by positron emission tomography (PET). Among the frontier challenges in 18F-radiochemistry are the interconnected goals of increasing synthetic efficiency and diversity in the construction of 18F-labelled radiotracers. 18F-Radioretrosynthetic strategies implemented to date are typically linear sequences of transformations designed with the aim of introducing the 18F-label ideally in the last step or at least as late as possible. Here we report that convergent 18F-radiochemistry allows for the rapid assembly of functionalised 18F-radiotracers from readily accessible 18F-labelled prosthetic groups. Using multicomponent reactions for proof of concept, Ugi-4CR, Passerini-3CR, Biginelli-3CR and Groebke-3CR were performed successfully using 18F-benzaldehydes and these highly convergent reactions delivered, in high radiochemical yield (RCY), structurally complex 18F-radiotracers with the label positioned on an aryl motif not responsive to direct nucleophilic fluorination. These data establish an unprecedented connection between radiochemistry for PET and the field of multicomponent chemistry and demonstrate that convergent retroradiosynthesis is a powerful strategy expanding dramatically the scope of 18F-prosthetic group radiochemistry. The preparation of 18F-labelled prosthetic groups from [18F]fluoride ion is commonly performed in many labelling laboratories, so the concept of convergent 18F-radiosynthesis can easily be applied immediately.

5. Gold Catalysis and Fluorine

M. N. Hopkinson, A. D. Gee, V. Gouverneur*

Israel Journal of Chemistry | 2010

Isr. J. Chem. 2010, 50, 675-690

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Performing gold-catalyzed organic transformations in the presence of fluorinating reagents can lead to both fluorinated and non-fluorinated products. Gold(I) complexes can activate alkynes towards nucleophilic attack by fluoride leading to fluoroalkenes under mild conditions. Fluorinated products can also be prepared upon performing gold-catalyzed transformations in the presence of electrophilic sources of fluorine. In most cases, however, the combination of gold and electrophilic fluorinating reagents does not lead to fluorination but delivers products of oxidative homo- or cross-coupling. In these processes the “F+” source is likely acting as a sacrificial two-electron external oxidant performing the key oxidation of gold(I) to gold(III) in the redox cycle. Oxidative coupling is an emerging field of gold catalysis which, when combined with the well-established reactivity of gold as a soft π-acid, holds promise as a mild and efficient method for the construction of complex organic molecules.

4. Gold-Catalyzed Cascade Cyclization-Oxidative Alkynylation of Allenoates

M. N. Hopkinson, J. E. Ross, G. T. Giuffredi, A. D. Gee, V. Gouverneur*

Organic Letters | 2010

Org. Lett. 2010, 12, 4904-4907

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A gold(I)-catalyzed cascade cyclization−oxidative cross-coupling process has been applied to prepare β-alkynyl-γ-butenolides directly from allenoates and various terminal alkynes. Following an initial gold-catalyzed C−O bond forming allenoate cyclization, a mechanism based on a AuI/AuIII redox cycle has been proposed with Selectfluor acting as the external oxidant.

3. Gold-Catalyzed Diastereoselective Synthesis of α-Fluoroenones from Propargyl Acetates

M. N. Hopkinson, G. T. Giuffredi, A. D. Gee, V. Gouverneur*

Synlett | 2010

Synlett 2010, 2737-2742

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A diastereoselective preparation of α-fluoroenones from propargyl acetates has been developed proceeding via a gold-catalyzed rearrangement-fluorination cascade. Control reactions are consistent with a mechanism involving a gold-mediated 3,3-sigmatropic shift followed by a direct, nongold-catalyzed electrophilic fluorination of the allenyl acetate intermediate.

2. Gold-Catalyzed Intramolecular Oxidative Cross-Coupling of Non-Activated Arenes

M. N. Hopkinson, A. Tessier, A. Salisbury, G. T. Giuffredi, L. E. Combettes, A. D. Gee, V. Gouverneur*

Chemistry - A European Journal | 2010

Chem. Eur. J. 2010, 16, 4739-4743

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An (Au)some coupling! Gold-catalyzed cascade C-O cyclizations of benzyl-substituted allenoate esters followed by intramolecular oxidative C-C cross-coupling involving aryl C-H functionalization were performed with Selectfluor as the oxidant (see scheme). This operationally simple and mild procedure benefits from complete axis-to-center chirality transfer and allows for the preparation of surprisingly uncommon tricyclic motifs.

1. Diastereoselective Fluorination of Silylated 1,2-Oxazines to Access Fluorinated N,O-Heterocycles

Y.-h. Lam, M. N. Hopkinson, S. J. Stanway, V. Gouverneur*

Synlett | 2007

Synlett 2007, 3022-3026

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The electrophilic fluorination of silylated N,O-heterocycles, prepared from a nitroso-Diels-Alder reaction of silylated dienes, afforded fluorinated 1,2-oxazines with the fluorine substituent on a stereogenic centre in moderate to high diastereoselectivities. The sense and level of diastereocontrol were found to be dependent of the substitution pattern of the heterocycle.