7th CaRLa Winter School 2014...

7th CaRLa Winter School 2014 Heidelberg

February 22 – 28, 2014

Final Program

Welcome to the 7th CaRLa Winter School Welcome to the picturesque town of Heidelberg, welcome to CaRLa, the joint research laboratory of BASF and University of Heidelberg and welcome to our CaRLa Winter School on Homogeneous Catalysis!

With our Winter School, we aim to foster intense scientific exchange between established and young researchers in the field of homogeneous catalysis.

The conference takes place from February 22-28, 2014 at the German-American-Institute downtown Heidelberg, within walking distance to the old town.

Our scientific program consists of 1 Keynote Lecture, 10 lectures, 10 problem set sessions and poster presentations.

The days are organized as a morning and afternoon session. Each session is divided into two parts; the first part consists of a scientific lecture while the second part has a more educational focus. Between the two sessions of the day, we have scheduled a prolonged lunch break for individual use. In the evening, we have planned short poster presentations of selected poster contributions, after which a light dinner is served in parallel with the poster sessions. All presentations are scheduled to leave enough room for discussion and we encourage every participant to use this time to make our Winter School an exciting event for science. The conference is fully sponsored by BASF and we are happy to announce, that we will have the opportunity for making an excursion to BASF on Thursday afternoon. We hope that all participants will have a pleasant and scientifically stimulating stay in Heidelberg during our Winter School. If we can assist you in any way to make your stay in Heidelberg more pleasant, please do not hesitate to contact us

Michael Limbach Peter Hofmann

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Saturday, 22nd February

until 16:00 Arrival and Welcome Coffee

16:45 Welcome Address A. Stephen K. Hashmi Prorector Research of Heidelberg University

17:00 Key Note Lecture Peter Schuhmacher “Raw Material Change in the President Process Research & Chemical Chemical Industry” Engineering BASF SE

18:00 Light Dinner and “Get-together”

Sunday, 23rd February

9:00 Lecture: Design of Selective Catalytic Cycles that are Fuelled by a Proton (Amir Hoveyda)

10:00 Coffee Break

10:15 Training Session: Design of Mo-, W- and Ru-Based Stereogenic-at-Metal Complexes for Z-Selective Olefin Metathesis Reactions (Amir Hoveyda)

11:15 Coffee Break

11:30 Flash Poster Presentations: Posters 2, 4, 6, 8, 10

12:00 Free Time (Lunch)

14:30 Lecture: Catalytic Systems for Aerobic Oxidation and Tandem Dehydrogenation / Hydrogenation (Catherine S. Cazin)

15:30 Coffee Break

15:45 Training Session: Green Chemistry: Concepts and Limitations (Catherine S. Cazin)

16:45 Coffee Break


17:30 Poster Session including light dinner

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Monday, 24th February

9:00 Lecture: Why Do Weaker Metal-Carbon Bonds Lead to More Stable Complexes? What’s going on? (William D. Jones)

10:00 Coffee Break

10:15 Training Session: Determination of Kinetic and Thermodynamic Parameters in Organometallic Reactions (William D. Jones)

11:15 Coffee Break



14:30 Lecture: Recent Advances in Gold-NHC Catalysis (Steve Nolan)

15:30 Coffee Break

15:45 Training Session: A Tutorial on NHCs (Steve Nolan)

16:45 Coffee Break


17:30 Poster Session including light dinner

Tuesday, 25th February

9:00 Lecture: Theoretical Studies of Biocatatysis (Walter Thiel)

10:00 Coffee Break

10:15 Training Session: Theoretical Studies of Homogeneous Catalysis (Walter Thiel)

11:15 Coffee Break



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14:30 Lecture: Controlled Cross-Coupling Reactions Under Iron-Catalysis: New Mechanism, Reactivity and Selectivity (Masaharu Nakamura) 15:30 Coffee Break 15:45 Training Session: Iron-Catalyzed Aromatic Amination and Related Coupling

Reactions (Masaharu Nakamura)

16:45 Coffee Break 17:00 Flash Poster Presentations: Posters 32, 34, 36, 38, 40, 42 17:30 Poster Session including light dinner

Wednesday, 26th February 9:00 Lecture: Applied Organometallic Chemistry - Part 1: Menthol Synthesis (Rocco Paciello) 10:00 Coffee Break 10:15 Training Session: Applied Organometallic Chemistry - Part 2: CO2-

Hydrogenation (Rocco Paciello) 11:15 Coffee Break 11:30 Flash Poster Presentations: Posters 23, 25, 27, 29, 31 12:00 Free Time (Lunch) 14:30 Lecture: Base Metal Catalysis for Alkylation: Scope and Mechanism (Xile Hu) 15:30 Coffee Break 15:45 Training Session: Homogeneous CO2 Reduction: Is it possible to go beyond

Fundamental Research? (Xile Hu) 16:45 Coffee Break 17:00 Flash Poster Presentations: Posters 33, 35, 37, 39, 41 17:30 Poster Session including light dinner

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Thursday, 27th February

9:00 Lecture: From Butadiene to Adipic Aldehyde? Chasing an Industrial Dream Reaction Combining Experiment and Theory (Peter Hofmann)

10:00 Coffee Break

10:15 Training Session: Mechanistic Organometallic Chemistry (Peter Hoffmann)


13:00 Transfer to Ludwigshafen

13:30 Excursion of BASF’s Main Site in Ludwigshafen

18:00 Symposium Dinner at “Kulturbrauerei”

Friday, 28th February

9:00 Lecture: Rapid Assembly of Heterocycles by C-H Bond Functionalization (Jonathan Ellman)

10:00 Coffee Break

10:15 Training Session: Rh(III) Catalysis: Mechanisms, Scope and Applications (Jonathan Ellman)

11:15 Coffee Break

11:30 Poster Prize Ceremony & Closing Remarks

12:00 Departure

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Lectures & Training Sessions

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Raw Material Change in the Chemical Industry Peter Schuhmacher*

BASF SE, Process Research & Chemical Engineering, GC – M311, 67056 Ludwigshafen, Germany e-mail: [email protected]

At each time availability and price structure of the fossil raw materials coal, petroleum and natural gas have significantly influenced the technological basis and consequently the buildup and development of the chemical industry. In the energy industry a consistent raw material change from coal to oil and gas has occurred since the middle of the 20th Century. The reason for this change lies mainly in the simpler logistics as well as the versatile usefulness of oil and gas. Parallel to the change in the energy industry the raw material base of the chemical industry has been changed from coal to oil and gas. Olefins, which are produced mainly by steam cracking of naphtha, and aromatic hydrocarbons, are still the crucial raw materials for the majority of the value added chains of the chemical industry. Price volatility, regional distribution and the finite reserves of crude oil are the main drivers for the development of conversion technologies to utilize alternative raw materials, e.g. natural gas, coal, renewables and carbon dioxide as feedstocks for the chemical industry.

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Design of Selective Catalytic Cycles that are Fuelled by a Proton Amir Hoveyda*

Boston College, Department of Chemistry, Merkert Chemistry Center, Chestnut Hill, Massachusetts 02467, USA

e-mail: [email protected]

This lecture will be focused on a set of small organic molecules that catalyze reactions of readily available unsaturated organoboron reagents with a variety of imines and carbonyls; products are amines and alcohols of high enantiomeric purity, intermediates used to synthesize many biologically active molecules. A distinguishing feature of the catalyst class is a proton embedded within their structure.

It will be demonstrated that the electronic activation and structural organization caused by the presence of the imbedded proton influence every stage of the carbon-carbon bond forming process; this includes achieving high rates of catalyst regeneration and product release, typically obtained through rapid ligand exchange with metal-containing systems. The catalyst is derived from the abundant amino acid valine and prepared in significant quantities in four steps with cheap chemicals without the need for chromatography. Reactions are easily scalable, do not demand stringent conditions, can be performed with as little as 0.25 mole % catalyst in less than six hours at room temperature, furnishing products typically in >85% yield and ≥97:3 enantiomeric ratio.

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Design of Mo-, W- and Ru-Based Stereogenic-at-Metal Complexes for Z-Selective Olefin Metathesis Reactions

Amir Hoveyda* Boston College, Department of Chemistry, Merkert Chemistry Center, Chestnut Hill, Massachusetts

02467, USA e-mail: [email protected]

The need for reliable methods that furnish alkenes efficiently and stereoselectively continues to represent a difficult and compelling challenge in chemical synthesis. Particularly scarce as protocols that are catalytic or deliver thermodynamically less favored Z-alkenes. Catalytic olefin metathesis offers exceptionally efficient pathways for synthesis of alkenes. Among various types of olefin metathesis, cross-metathesis (CM) of two different terminal alkenes and ring-closing metathesis (RCM) constitute remarkably attractive and efficient strategies for synthesis of acyclic or macrocyclic di- or more highly substituted alkenes. What renders the goal of a Z-selective CM or RCM a particularly daunting challenge is that it is the higher energy isomer that is targeted.

In this lecture, the first examples of catalytic CM and RCM transformations will be presented that a range of highly versatile alkenes with exceptional Z selectivity (typically >90%). Design and use of stereogenic-at-Mo, W and Ru complexes, developed in our laboratories, will be a key part of the presentation. Through utilization of unique structural attributes of such catalysts, levels of reactivity and selectivity that were previously entirely out of reach can be easily achieved. The critical electronic and steric characteristics of the catalysts and applications of the Z-selective cross-metathesis reactions to synthesis of several molecules of significance to biology and medicine will be unveiled.

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Catalytic systems for aerobic oxidation and tandem dehydrogenation/hydrogenation

Catherine S. J. Cazin*EaStCHEM School of Chemistry, University of St Andrews, St Andrews, KY16 9ST, UK


The use of Transition Metal complexes bearing mixed ligand systems can lead to synergism, hence increasing either catalyst stability or more interestingly catalytic performance. Our approach has been to explore whether the combination of a N-heterocyclic carbene and a P-donor ligand could lead to improvement of catalytic activity. Out of the systems investigated, we will focus on advances made using this approach with palladium for the aerobic oxidation of alcohols,1 and for the reduction of multiple bonds. For the latter, systems based on molecular hydrogen2 will first be discussed, followed by tandem processes using greener sources of hydrogen: NH3BH3

3 and HCOOH.4 The isolation of key catalytic species will be presented, with mechanistic and computational studies, delineating a tandem sequence rather than a transfer hydrogenation mechanism.

[1] V. Jurčík, T. E. Schmid, Q. Dumont, A. M. Z. Slawin, C. S. J. Cazin, Dalton Trans. 2012, 41, 12619-12623.

[2] V. Jurčík, S. P. Nolan, C. S. J. Cazin, Chem. Eur. J. 2009, 15, 2509-2511. [3] C. E. Hartmann, V. Jurčík, O. Songis, C. S. J. Cazin, Chem. Commun. 2013, 49, 1005-1007. [4] J.Broggi, V. Jurčík, O. Songis, A. Poater, L. Cavallo, A. M. Z. Slawin, C. S. J. Cazin, J. Am.

Chem. Soc. 2013, 135, 4588-4591.

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Green Chemistry: Concepts and limitations Catherine S. J. Cazin*

EaStCHEM School of Chemistry, University of St Andrews, St Andrews, KY16 9ST, UK e-mail: [email protected]

The aim of this training session is to examine the concepts and parameters involved in a greener approach to chemistry.

The lecture will cover the 12 principles of Green Chemistry and Life Cycle Assessment.1 Case studies will be discussed.

[1] Green Chemistry: Theory and Practice by Paul Anastas and John Warner (23 Mar 2000) Oxford University Press.

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Why Do Weaker Metal-Carbon Bonds Lead to More Stable Complexes? What's Going On?

Yunzhe Jiao, Meagan E. Evans, James Morris, William W. Brennessel, William D. Jones*

Department of Chemistry, University of Rochester, Rochester, NY 14627, USA e-mail: [email protected]

A series of kinetic measurements of Tp'Rh(CNneopentyl)(R)H complexes (Tp' = tris-(3,5-dimethylpyrazolyl)borate) where R = alkyl, aryl, vinyl, benzyl, allyl, and CH2X (X= CN, C≡CMe, CH2C(=O)CH3, and others) have been used to determine relative metal-carbon bond energies in these compounds. A thermodynamic analysis allows for the extraction of an increase in bond energy of ~7 kcal/mol for R groups in which the corresponding anion is resonance stabilized. This increase in bond strength is associated with an increase in the ionic contribution to metal-carbon bonding. Trends will be analyzed in terms of inductive vs. resonance contributions to the bonding.1 These studies have been extended to complexes with other spectator ligands in place of isocyanide, including PMe3

2 and P(OMe)3.3

[1] Y. Jiao, M. E. Evans, J. Morris, W. W. Brennessel, W. D. Jones, J. Am. Chem. Soc. 2013, 135, 6994-7004.

[2] Y. Jiao, J. Morris, W. W. Brennessel, W. D. Jones, J. Am. Chem. Soc. 2013, 135, 16198-16212. [3] Y. Jiao, W. W. Brennessel, W. D. Jones, Chem. Sci. 2013, 4, 804-812.

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Determination of Kinetic and Thermodynamic Parameters in Organometallic Reactions

William D. Jones*Department of Chemistry, University of Rochester, Rochester, NY 14627 USA


Determination of thermodynamic parameters for organometallic reactions can provide useful information about the intermediates and mechanism(s) of reaction. In this presentation, a review of kinetic methods will be presented using examples from the literature we have encountered over the past three decades. Worked solutions for each problem will be reviewed. Specific examples will include approach to equilibrium, NMR methods, sequential and parallel reactions, isotope effects, deuterium scrambling, and chemical simulation of complex reactions. From these specific examples, and by examination of the details of the kinetic fits, a general understanding of the use of free energy to express reaction thermodynamics will be obtained.

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Recent advances in gold-NHC catalysis Steven P. Nolan*

EaStCHEM School of Chemistry, University of St Andrews, St Andrews, UK KY16 9ST e-mail: [email protected]

Recent advances in the use of well-defined gold complexes enabling the activation of C-H bonds and CO2 will be discussed.1,2,3 The specific gold systems investigated in this study bear the now ubiquitous N-heterocyclic carbene ligands. Ligand properties will be addressed in the context of the propensity of gold to activate C-H bonds. The synthesis of digold complexes whether gem-digold or σ,π diacetylide complexes will be presented. Furthermore the reactivity of these species and their role in organogold catalysis will be discussed. More recent advances using well- defined gold-NHC systems will also be presented.

[1] I. I. F. Boogaerts, S. P. Nolan, J. Am. Chem. Soc. 2010, 132, 8858-8859. [2] Y. Oonishi, A. Gómez-Suárez, A. R. Martin, S. P. Nolan, Angew. Chem. Int. Ed. 2013, 52, 9767-

9770. [3] S. P. Nolan, Acc. Chem. Res. 2011, 44, 91-100.

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A Tutorial on NHCs Steven P. Nolan*

EaStCHEM School of Chemistry, University of St Andrews, St Andrews, UK KY16 9ST e-mail: [email protected]

The N-heterocyclic carbenes (NHCs) have become ubiquitous in organometallic and homogeneous catalysis. A historic look at their development and synthesis will be presented as well as a description of their physical/electronic and steric properties.

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Theoretical Studies of Biocatatysis Walter Thiel*

Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim, Germany e-mail: [email protected]

Combined quantum mechanical/molecular mechanical (QM/MM) approaches have emerged as the method of choice for treating local electronic events in large molecular systems, for example, chemical reactions in enzymes or photoinduced processes in biomolecules. The lecture will outline the theoretical background and commonly chosen strategies for QM/MM studies of enzymatic reactions1 and recent extensions to three-layer QM/MM/continuum approaches.2,3 It will then describe some of our work on biocatalysis by enzymes which includes mechanistic studies on cytochrome P450cam,4 xanthine oxidases,5 cyclohexanone monooxygenase,6,7 glycosyltransferases,8 tungsten-dependent acetylene hydratase,9 fosfomycin,10 and lysine-specific demethylase 1 (LSD1).11 The examples presented will illustrate the chemical insights and the improved mechanistic understanding of enzymatic reactions that can be provided by QM/MM calculations.

[1] H. M. Senn, W. Thiel, Angew. Chem. Int. Ed. 2009, 48, 1198-1229. [2] T. Benighaus, W. Thiel, J. Chem. Theory Comput. 2011, 7, 238-249. [3] E. Boulanger, W. Thiel, J. Chem. Theory Comput. 2012, 8, 4527-4538. [4] S. Shaik, S. Cohen, Y. Wang, H. Chen, D. Kumar, W. Thiel, Chem. Rev. 2010, 110, 949-1017. [5] S. Metz, W. Thiel, Coord. Chem. Rev. 2011, 255, 1085-1103. [6] I. Polyak, M. T. Reetz, W. Thiel, J. Am. Chem. Soc. 2012, 134, 2732-2741. [7] I. Polyak, M. T. Reetz, W. Thiel, J. Phys. Chem. B 2013, 117, 4993-5001. [8] H. Gomez, I. Polyak, W. Thiel, J. M. Lluch, L. Masgrau, J. Am. Chem. Soc. 2012, 134, 4743-4752. [9] R.-Z. Liao, W. Thiel, J. Chem. Theory Comput. 2012, 8, 3793-3803. [10] R.-Z. Liao, W. Thiel, J. Phys. Chem. B 2013, 117, 1326-1336. [11] B. Karasulu, M. Patil, W. Thiel, J. Am. Chem. Soc.2013, 135, 13400-13413.

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Theoretical Studies of Homogeneous Catalysis Walter Thiel*

Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim, Germany e-mail: [email protected]

Reaction pathways in homogeneous catalysis are nowadays often computed using density functional theory (DFT) and suitably chosen model systems (normally 50-100 atoms). It is planned to discuss the DFT approach to catalysis in an interactive seminar, covering both methodological aspects and illustrative applications related to our research. Possible topics include Rh-catalyzed asymmetric hydrogenation, metallocene-catalyzed olefin polymerization, and Pd-catalyzed cross coupling reactions.

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Controlled Cross-Coupling Reactions Under Iron-Catalysis: New Mechanism, Reactivity and Selectivity

Masaharu Nakamura*International Research Center for Elements Science (IRCELS), Institute for Chemical Research, Kyoto

University, Uji, Kyoto 611-0011, Japan e-mail: [email protected]

Iron-catalyzed cross-coupling reactions have been studied intensively in recent years. This is due to the practical benefits of the cheap and less toxic iron as well as iron’s high reactivity and unique selectivity for the coupling of alkyl halides, which are very often superior to those of the conventional palladium and nickel catalysts. The coupling reaction has been shown to proceed via a nonconventional oxidative mechanism, which involves an Fe+II–Fe+III redox and generation of an alkyl radical intermediate. Based on mechanistic studies on the reaction of organoiron species with alkyl halides, we have designed and developed novel iron-phosphine complexes possessing a bulky o-phenylenebisphosphine, such as 1. The iron catalysts have proven effective for selective coupling of various combinations of alkyl halides and organometallic reagents.1

[1] Related papers: a) S. Kawamura, T. Kawabata, K. Ishizuka, M. Nakamura, Chem. Commun. 2012, 48, 9376; b) T. Hatakeyama, Y. Okada, Y. Yoshimoto, M. Nakamura, Angew. Chem. Int. Ed. 2011, 50, 10973; c) T. Hatakeyama, T. Hashimoto, Y. Kondo, Y. Fujiwara, H. Seike, H. Takaya, Y. Tamada, T. Ono, M. Nakamura, J. Am. Chem. Soc. 2010, 132, 10674.

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Iron-Catalyzed Aromatic Amination and Related Coupling Reactions Masaharu Nakamura*

International Research Center for Elements Science (IRCELS), Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan


Transition-metal catalyzed aromatic amination is a wide-spreading method for the synthesis of functional arylamines. We have developed novel iron-catalyzed amination reactions of various aryl bromides for the synthesis of diaryl- and triarylamines,1 recurrent core units in pharmaceuticals as well as organic electronic materials. The present method is simple and free of precious and expensive metals and ligands, thus providing facile access to variety of arylamines. In this training session, novel ortho-C–H amination and arylation reactions of diarylamines, which we have unexpectedly found in the course of the study, will be discussed intereactively.

[1] T. Hatakeyama, R. Imayoshi, Y. Yoshimoto, S. K. Ghorai, S. K. Jin, H. Takaya, K. Norisuye, Y. Sohrin, M. Nakamura, J. Am. Chem. Soc. 2012, 134, 20262.

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Applied Organometallic Chemistry Part 1: Menthol Synthesis

Part 2: CO2-Hydrogenation Rocco Paciello*

BASF SE, Synthesis and Homogeneous Catalysis Department, GCS/H – M313, 67056 Ludwigshafen, Germany


Homogeneous catalysis research at BASF is characterized by a focus on organometallic chemistry closely coupled with process engineering. The strength of this approach will be demonstrated using selected examples.

An efficient 3-step route to L-menthol starting from citral has been realized at BASF.

A continuous process for asymmetric hydrogenation was developed as the first step. The key observations in process development will be correlated with the behavior of the catalyst system at a molecular level.

The use of CO2 as a C1-building block, in particular, the hydrogenation of CO2 to formic acid, is being investigated. A new process concept combines an efficient recycling of the active ruthenium catalyst with the isolation of formic acid. This is achieved using a carefully matched combination of solvent, amine base and lipophilic catalyst and by exploiting the properties and phase behaviour of these components. Further extensions of this chemistry to other catalysts and other products will also be discussed.

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Base metal catalysis for alkylation: scope and mechanism Xile Hu*

Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland e-mail: [email protected]

Alkyl halides are challenging substrates for cross coupling reactions because they are resistant to oxidative addition and because metal alkyl intermediate species are prone to beta-H elimination. Despite recent progress in this area, the scope and mechanistic understanding of coupling reactions of alkyl halides are limited. We have prepared well-defined Ni catalysts that catalyze the coupling of non-activated alkyl halides and related direct alkylation reactions.1 We have also developed copper and iron catalysts that catalyze similar alkylation reactions.2 In this talk, I will present the scope and mechanism of this emerging class of base metal catalysis.

[1] O. Vechorkin, X. L. Hu, Angew. Chem. Int. Ed. 2009, 48, 2937-2940; O. Vechorkin, V. Proust, X. L. Hu, J. Am. Chem. Soc. 2009, 131, 9756-9766; O. Vechorkin, A. Godinat, R. Scopelliti, X. L. Hu, Angew. Chem. Int. Ed. 2011, 50, 11777-11781; P. Ren, O. Vechorkin, K. von Allmen, R. Scopelliti, X. L. Hu, J. Am. Chem. Soc. 2011, 133, 7084-7095; O. Vechorkin, D. Barmaz, V. Proust, X. L. Hu, J. Am. Chem. Soc. 2009, 131, 12078-12079; O. Vechorkin, V. Proust, X. L. Hu, Angew. Chem. Int. Ed. 2010, 49, 3061-3064; J. Breitenfeld, J. Ruiz, M. D. Wodrich, X. L. Hu J. Am. Chem. Soc. 2013, 135, 12004-12012.

[2] P. Ren, L.-A. Stern, X. L. Hu, Angew. Chem. Int. Ed. 2012, 51, 9110-9113; P. Ren, I. Salihu, R. Scopelliti, X. L. Hu; Org. Lett. 2012, 14, 1748-1751; C. W. Cheung, X. L. Hu, unpublished results.

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mailto:[email protected]

Homogeneous CO2 reduction: Is it possible to go beyond fundamental research? Xile Hu*

Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland e-mail: [email protected]

Carbon dioxide utilization is a popular topic in academia and industry. Among various ways of CO2 utilization, the reduction of CO2 to fuels or high value chemical products is particularly interesting because such a process is potentially scalable to a degree that would reduce the anthropogenic CO2 emission. In the area of homogeneous catalysis, the following reactions are most relevant: hydrogenation of CO2 to make formate and electrocatalytic reduction of CO2 to make CO or formate. There is significant advance in both areas, where apparently efficient and selective catalysts are reported. The design of these catalysts reflects the state of the art in catalyst development. Whether these processes are industrially relevant remain to be proven. In this tutorial, I will present several typical examples of homogeneous CO2 reduction including electro-reduction. The audience is invited to discuss whether homogenous CO2 reduction would likely go beyond academic curiosity.

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From Butadiene to Adipic Aldehyde? Chasing an Industrial Dream Reaction Combining Experiment and Theory.

Peter Hofmann*a,b aOrganisch-Chemisches Institut, Universität Heidelberg, Germany

bCaRLa (Catalysis Research Laboratory), Heidelberg, Germany e-mail: [email protected]

Hydroformylation (the “Oxo-Reaction”, “Oxosynthese”), discovered by Otto Roelen (Co), represents one of the largest applications of homogeneous transition metal (Rh)1 catalysis in industry, with more than 10 million tons of aldehydes produced per year. The substrates commonly employed are terminal or internal monoolefins. Despite the atom economy of the oxo process, and despite many research efforts since around 1950, the 1,4-dihydroformylation of butadiene to adipic aldehyde still represents a “dream reaction” of chemical industry.1

Based upon a novel, highly active and highly n-selective (n:i up to 300) ligand family for Rh-catalyzed hydroformylation of terminal olefins,2 the results of broad experimental and theoretical studies directed towards the synthesis of adipic aldehyde will be discussed in detail.3

[1] P. W. N. M. v. Leeuwen, C. Claver (Eds.), Rhodium Catalyzed Hydroformylation, Springer, 2002.

[2] W. Ahlers, M. Röper, P. Hofmann, D. C. M. Warth, R. Paciello, WO 01/58589 A1 (BASF SE). [3] S. E. Smith, T. Rosendahl, P. Hofmann, Organometallics 2011, 30, 3643-3651.

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Rapid Assembly of Heterocycles by C-H Bond Functionalization Jonathan Ellman*

Department of Chemistry, Yale University e-mail: [email protected]

Methods for the rapid assembly of heterocycles from simple and readily available inputs by Rh(I)- and Rh(III)-catalyzed C-H bond functionalization will be reported. New routes to aromatic heterocycles relevant to pharmaceutical and natural product synthesis such as furans, pyrroles, indazoles, phenazines, acridines and phthalides will be described.1,2,3 In addition, cascade processes will be presented for convergent and stereoselective entry to densely substituted piperidines, including structures containing adjacent quaternary centers and bridged bicyclic systems.4,5 The scope and mechanisms for these new methods will be provided. Their utility will also be illustrated by syntheses of spectroscopic probes, bioactive natural products and pharmaceutical agents.

[1] Y. Lian, J. R. Hummel, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc. 2013, 135, 12548-12551. [2] Y. Lian, R. G. Bergman, L. D. Lavis, J. A. Ellman, J. Am. Chem. Soc. 2013, 135, 7122-7125. [3] Y. Lian, T. Huber, K. D. Hesp, R. G. Bergman, J. A. Ellman, Angew. Chem. Int. Ed. 2013, 52,

629-633. [4] S. Duttwyler, S. Chen, M. K. Takase, K. B. Wiberg, R. G. Bergman, J. A. Ellman, Science

2013, 339, 678-982. [5] M. A. Ischay, M. K. Takase, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc. 2013, 135, 2478-

2481.

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Rh(III) Catalysis: Mechanisms, Scope and Applications Ellman Jonathan*

Department of Chemistry, Yale University e-mail: [email protected]

Over the past several years Rh(III)-catalyzed C-H bond functionalization has been applied to a diverse range of different transformations using a large variety of coupling partners.1 Very broad functional group compatibility is typically observed adding to the attractiveness of these methods. This training session will focus on the mechanisms, scope and limitations for key classes of reactions, including C-H bond couplings with alkenes, alkynes, carbon-heteroatom π-bonds and azides. The use of oxidizing directing groups, enantioselective transformations and pharmaceutical applications will also be presented.

[1] For reviews that cover some aspects of this work, see: a) T. Satoh, M. Miura, Chem. Eur. J. 2010, 16, 11212-11222; b) G. Song, F. Weng, X. Li, Chem. Soc. Rev. 2012, 41, 3651-3678; c) F. W. Patureau, J. Wencel-Delord, F. Glorius, Aldrichimica Acta 2012, 45, 31-41.

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Poster Abstracts

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Poster 1

CaRLa – The Catalysis Research Laboratory Catalyzing the Cooperation Between Science and Industry

Peter Hofmann,a,b* Michael Limbacha,c* aCatalysis Research Laboratory, Im Neuenheimer Feld 584, 69120 Heidelberg,

Germany; bOrganisch-Chemisches Institut der Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany; cBASF SE, GCS/C – M313, 67056 Ludwigshafen, Germany

e-mail: [email protected], [email protected]

Innovation is an intersectoral topic. In this regard, public private partnerships are key instruments for improving a country’s innovativeness.

CaRLa is a new role model of research cooperation, in which BASF and the University of Heidelberg work closely together in a joint laboratory. In CaRLa, 6 postdocs of the university, supervised by Heidelberg faculty, together with 6 postdocs directed by BASF research units are working bench to bench to investigate basic research issues directed towards potential industrial applications in the field of transition metal based homogeneous catalysis. The goal of CaRLa is to facilitate the transfer of results from basic research towards applications in industry.

Catalysis is the most important chemical technology of the chemical industry. More than 80 percent of all chemical products come into contact with catalysts at least once during their synthesis. Research in the field of homogeneous catalysis without doubt has resulted in an exceptional track record of real innovations. Its potential spans a wide range from polymerization to hydroformylation, carbonylation, asymmetric hydrogenation, carbon-carbon or carbon-heteroatom bond formation to applications of homogeneously catalyzed metathesis.

In CaRLa, industry and academia jointly have identified interesting fields of research and challenging targets. CaRLa utilizes the expertise of its principal investigators to optimize a focused research portfolio covering contemporary topics of transition metal based homogeneous catalysis.

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Poster 2

Formation of Unusual 3-, 4-, and 5-Membered Metallacycles (Ti, Zr, Mo) by Reaction with Ynediamines

Ò. Àrias,a A. R. Petrov,a P. G. Jones,a U. Rosenthal,b M. Tamm*a

aInstitut für Anorganische und Analytische Chemie, Technische Universität Braunschweig, Hagenring 30,

D-38106 Braunschweig, Germany bLeibniz-Institut für Katalyse e.V. an der Universität Rostock, Albert-Einstein-Str. 29a, D-18059 Rostock,

Germany e-mail: [email protected]

Very recently, we explored the reactivity of ynediamines (R2N–C≡C–NR2) in organometallic chemistry, which is still in its infancy.1 In this context, the reaction of ynediamines with group 4 metallocenes afforded 3- and 5-membered metallacycles (1–4), as shown in Scheme 1. We observed that the zirconacyclopropene complexes 4a–4c are in equilibrium with their tetramethylpentafulvene tucked-in isomers 5a–5c. The formation of the latter implies an intramolecular C-H bond activation and hydrogen transfer to the alkyne moiety, which is unprecedented for isolated group 4 metallocenes.1b In addition, an unusual molybdenacyclobutadiene has been obtained upon the reaction of an ynediamine with a molybdenum alkyne metathesis catalyst.2

Cp2M

pippip

pippip

1: M = Ti2: M = Zr

Cp*2M

R

RZr

C5Me5 H

R

R

5a–5c

a: R = pipb: R = 4-Me-pipc: R = NEt2

Cp'2M

R RCp' = CpR = pip

Cp' = Cp*

pip = N3: M = Ti; R = pip4a–c: M = Zr

Scheme 1. Formation of ynediamine group 4 metallocene complexes 1-5.

[1] a) A. R. Petrov, T. Bannenberg, C. G. Daniliuc, P. G. Jones, M. Tamm, Dalton Trans. 2011, 40, 10503-10512; b) Ò. Àrias, A. R. Petrov, T. Bannenberg, K. Altenburger, P. Arndt, P. G. Jones, U.

Rosenthal, M. Tamm, J. Am. Chem. Soc. 2014, submitted. [2] B. Haberlag, M. Freytag, C. G. Dabiliuc, P. G. Jones, M. Tamm, Angew. Chem. Int. Ed. 2012, 51,

13019-13022; Angew. Chem. 2012, 124, 13195-13199.

29

Poster 3

Synthesis and Kinetics of Diphenylamido Palladium(II) Complexes Based on Biaryl Phosphine Ligands.

Pedro L. Arrechea,a Stephen L. Buchwald*a,b

aDepartment of Chemistry, Massachusetts Institute of Technology bDepartment of Chemistry, Massachusetts Institute of Technology


Reductive elimination of the amido complex was found to be the rate-determining

step for several cross-coupling reactions between aryl halides and diphenylamines using a RuPhos-based palladium catalyst. Consistent with previous work, both catalytic and stoichiometric kinetic studies indicated that electron-deficient aryl halides and nucleophilic diphenylamine derivatives favor reductive elimination. Reductive elimination as a function of biaryl ligand structure was investigated. It is believed the electronic nature of the “lower” aryl ring plays a critical role in the kinetics of reductive elimination.

30

Poster 4

PCsp2PNiOH Catalysts for the Selective Hydration of Nitriles to Amides Javier Borau-Garcia, Dmitry V. Gutsulyak, Warren E. Piers*

Department of Chemistry, University of Calgary, 2500 University Dr. NW Calgary, Alberta, Canada

T2N1N4


Catalytic hydration of nitriles can be seen as an atom economical route to amides. Selectivity of this reaction is hard to achieve since amides can undergo further hydration to the corresponding acid.1 We present the selective hydration of nitriles to amides catalyzed by the previously reported (iPr-PCsp2P)NiOH as well as its tBu and Cy substituted analogs.2 Mechanistic insights of the proposed catalytic cycle as well as the substrate scope of the reaction will be discussed.

(R')2P Ni P(R')2

OH

H

(R')2P Ni P(R')2

N

H

R

OH

RCN

(R')2P Ni P(R')2

N

H

R OH

(R')2P Ni P(R')2

N

H

HR

O

H2O

RCN

RC(O)NH2

R' = iPr, tBu, Cy

[1] T. J. Ahmed, M. M. K. Spring, D. R. Tyler, Coord. Chem. Rev. 2011, 255, 949-974.

[2] D. V. Gutsulyak, W. E. Piers, J. Borau-Garcia, M. Parvez, J. Am. Chem. Soc. 2013, 135,

11776-11779.

31

Poster 5

An Experimental and Computational Study into the Reactions of Small Bite Angle NHCP Ligands with Ruthenium: Coordination Chemistry, Catalytic Screening,

and Decomposition Pathways Christopher Brown,a Philipp N. Plessow,a Frank Rominger,b Peter Hofmann*a,b

aCatalysis Research Laboratory (CaRLa), University of Heidelberg, Im Neuenheimer Feld 584, D-69120

Heidelberg, Germany bOrganisch-Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg,

Germany


Olefin metathesis has become a general tool for the construction of carbon-carbon bonds. In previous work, Hofmann and co-workers reported cationic ruthenium carbene complexes based on the bulky and electron-rich ligands dtbpm and dtbpe. They show exceptionally high activity in ROMP, even at ppm-range catalyst concentrations.1 In light of the high activity of these bisphosphine-based complexes and the advantages which NHCs displayed for 2nd generation Grubbs catalysts, the recently developed bidentate 4-membered chelate NHC-Phosphine ligands (NHCPs) have been applied to Ru with an aim towards catalytic olefin metathesis. Such NHCP ligands have a computationally proposed low energy pathway via NHCP-phosphine dissociation to a neutral 14e- ruthenium species. Initial coordination chemistry, observed decomposition pathways and preliminary catalytic screening will be described.

RuClCl

tBu2P

N

NR R'

RuClCl

tBu2P

py

py

N

NR

Ph

N NR PtBu2

[Ru] [Ru]

[1] S. Hansen, F. Rominger, M. Metz, P. Hofmann, Chem. Eur. J. 1999, 5, 557-566.

32

Poster 6

Alkaline Earth Borohydrides as Ring-Opening Polymerisation Catalysts Richard Collins, Junjuda Unruangsri, Philip Mountford*

Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK


The ring-opening polymerisation (ROP) of ε-caprolactone (ε-CL) and lactide (LA) to form the corresponding polymers PCL and PLA, respectively, has attracted sustained interest over the last 15 years. A number of approaches to the synthesis of biocompatible and biodegradable polyesters via ROP are known, but the most common is via a coordination-insertion mechanism mediated through a M–polymeryl bond.1

Group 2 metals have attracted renewed interest owing to their low toxicity and (for catalysts operating by a coordination-insertion mechanism) the polarity of the initiating, and subsequently propagating, M–X bond.2

Herein, we report the synthesis and solid state structures of a congeneric series of β-diketiminate-supported group 2 tetrahydroborate complexes and a magnesium bis(phosphinimino)methanide analogue, together with a study of the ε-Cl and rac-LA ring-opening polymerisation capability of the magnesium and calcium complexes.3

Mg

N

N

P

P

Ar'

Ar'

THF

BH4

THFPh2

Ph2

Ca

N

N

Ar'

Ar'

THF

BH4

THFMg

N

N

Ar'

Ar'

BH4

THF

1

Sr

N

N

Ar'

Ar'

THF

BH4

THF

432

Figure 1. Group 2 tetrahydroborate catalysts.

[1] Recent reviews: C. A. Wheaton, P. G. Hayes, B. J. Ireland, Dalton Trans. 2009, 4832; R. H. Platel, L. M. Hodgson, C. K. Williams, Polym. Rev. 2008, 48, 11; D. Bourissou, Chem. Rev. 2004, 104, 6147; B. J. O'Keefe, M. A. Hillmyer, W. B. Tolman, J. Chem. Soc., Dalton Trans. 2001, 2215; M. J. Stanford, A. P. Dove, Chem. Soc. Rev. 2010, 39, 486.

[2] C. A. Wheaton, P. G. Hayes, B. J. Ireland, Dalton Trans. 2009, 4832; S. Harder, Chem. Rev., 2010, 110, 3852.

[3] R. A. Collins, J. Unruangsri, P. Mountford, Dalton Trans. 2012, 42, 759.

33


Poster 7

The Synthesis of a New Class of Chiral Pincer Ligands and Their Applications in Enantioselective Catalysis

Qing-Hai Deng,a,b Hubert Wadepohl,b Lutz H. Gade*a,b

aCatalysis Research Laboratory (CaRLa), Im Neuenheimer Feld 584, 69120 Heidelberg, Germany bAnorganisch-Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg,

Germany


A new class of chiral tridentate N-donor pincer ligands, bis(oxazolinyl- methylidene)isoindolines (boxmi) has been synthesized in three steps starting from readily available phthalimides. 1 These ligands were applied in a series of enantioselective catalysis such as Ni-catalyzed fluorination of β-ketoesters and oxindoles,1 Cu-catalyzed alkylation of β-ketoesters and subsequent cyclization to spirolactones/bi-spirolactones, 2 a Cu-catalyzed trifluoromethylation of β-ketoesters,2b and Fe-catalyzed azidation of β-ketoesters and oxindoles.2c

NBoc

O

H R1R2

O

CO2R3

H

R1

R2 nn = 1, 2

O

CO2R3

R4

R1

R2

O

CO2R3

CF3

R1

R2 nn = 1, 2

NBoc

O

F R1R2

O

CO2R3

F

R1

R2 nn = 1, 2

NBoc

O

N3 R1R2

O

CO2R3

N3

R1

R2 nn = 1, 2

Ni Cu

CuFe

Fluorination

Alkylation &Cyclization

TrifluoromethylationAzidation

up to >99% ee

up to >99% ee

up to 94% eeup to 99% ee

(PhO2S)2NF R4OH

IN3 O IF3C O

NH

H

H

N

O

O

N

R2

R2

R1

R1

boxmi

[1] Q.-H. Deng, H. Wadepohl, L. H. Gade, Chem. Eur. J. 2011, 17, 14922.

[2] a) Q.-H. Deng, H. Wadepohl, L. H. Gade, J. Am. Chem. Soc. 2012, 134, 2946; b) Q.-H. Deng, H. Wadepohl,

L. H. Gade, J. Am. Chem. Soc. 2012, 134, 10769; c) Q.-H. Deng, T. Bleith, H. Wadepohl, L. H. Gade, J. Am.

Chem. Soc. 2013, 135, 5356.

34

Poster 8

A Mechanistic Investigation of 1-Octanol Amination Catalyzed by Ruthenium(II) Triphos Complexes

Eric J. Derrah,a,b Philipp N. Plessow,a,b Mathias Schelwies,b Peter Hofmann,c Michael Limbach*a,b

aCaRLa – Catalysis Research Laboratory, Heidelberg, Germany; bBASF SE, Synthesis & Homogeneous

Catalysis, Ludwigshafen, Germany; cOrganisch-Chemisches Institut, Ruprecht-Karls-UniversitätHeidelberg, Heidelberg, Germany


Transition metal catalyzed N-alkylation of ammonia with alcohols is an attractive method for amine formation due to its use of inexpensive and abundant starting materials.1,2 In this context, a ruthenium triphos complex has been found to be selective for the formation of octylamine from 1-octanol and ammonia. Although this system is highly promising, catalytic activity remains low relative to other complexes reported in the literature.2 Novel symmetrical and unsymmetrical derivatives of the triphos ligand have been investigated in an effort to improve catalytic activity. Mechanistic and theoretical studies will be presented, which implicate that a ruthenium dihydride complex may be the active species.

[1] D. Balcells, A. Nova, E. Clot, D. Gnanamgari, R. H. Crabtree, O. Eisenstein, Organometallics 2008, 27, 2529-2535.

[2] C. Gundathan, D. Milstein, Angew. Chem. Int. Ed. 2008, 47, 8661.

35

Poster 9

New RhIII-H Complexes Bearing a N-heterocyclic Carbene Ligand as Catalysts in H/D Exchange of α-Olefins. A Structure-Activity Study

Andrea Di Giuseppe, Ricardo Castarlenas, Jesus J. Perez-Torrente, Fernando J. Lahoz, Luis A. Oro*

Departamento Química Inorgánica, Instituto Síntesis Química y Catálisis Homogénea, Universidad de

Zaragoza – CSIC, C/ Pedro Cerbuna 12, 50009 Zaragoza (Spain) e-mail: [email protected]

One of the major challenges in modern chemistry is the design of improved catalysts

for controlled and selective C-H functionalization. In this context, H/D exchange reactions are valuable transformations for the preparation of isotopically labeled compounds. Recently our group has developed a new homogenous catalytic system based on RhIII-H complexes bearing a N-heterocyclic carbene ligand.1 This system resulted very active and selective for the vinylic H/D exchange reaction of aromatic α-olefins. Indeed, these catalysts are able to deuterate specifically the β-position with a very high regioselectivity. In this work the role of the different ligands bonded to the RhIII-H motif were studied, in order to improve both activity and selectivity of the catalyst. For that reason several complexes of RhIII-H, with ligands having different electronics and steric properties, have been prepared and characterized. Finally the catalytic test of the complexes allowed highlighting the relationship between complex structure and its catalytic properties.

[1] A. Di Giuseppe, R. Castarlenas, J. J. Perez-Torrente, V. Polo, L. A. Oro, Angew. Chem. Int. Ed.

2011, 50, 3938-3942.

36

Poster 10

Synthesis of (+)-Schisanwilsonene A Morgane Gaydou,a Ricarda E. Miller,a Nicolas Delpont,a Julien Ceccon,a Antonio M.

Echavarren*a,b

aInstitute of Chemical Research of Catalonia (ICIQ) Av. Països Catalans 16, 43007 Tarragona (Spain) bDepartament de Química Analítica i Química Orgànica Universitat Rovira i Virgili C/Marcel·li Domingo

s/n, 43007 Tarragona (Spain)


Gold(I) complexes catalyze a new type of intramolecular 1,5-migration of

propargylic alcohols, ethers and silyl ethers.1 This methodology has been applied for the total synthesis of the natural sesquiterpene (+)-schisanwilsonene A. This compound was isolated in 2009,2 and, until our report, no synthesis has been described. The key reaction sequence catalyzed by gold is a fully stereoselective tandem cyclization/1,5-migration/intermolecular cyclopropanation.3

The first synthesis of the enantioenriched schisanwilsonene A has been successfully achieved in 13 steps with an overall yield of 4.5%.

[1] E. Jiménez-Núñez, M. Raducan, T. Lauterbach, K. Molawi, C. R. Solorio, A. M. Echavarren,

Angew. Chem. Int. Ed. 2009, 48, 6152-6155.

[2] W.-H. Ma, H. Huang, P. Zhou, D.-F. Chen, J. Nat. Prod. 2009, 72, 676-678. [3] M. Gaydou, R. E. Miller, N. Delpont, J. Ceccon, A. M. Echavarren, Angew. Chem. Int. Ed. 2013,

52, 6396-6399.

37

Poster 11

First Enantioselective Total Synthesis of Lythranidine Konrad Gebauer, Alois Fürstner*

Max-Planck Institut für Kohlenforschung, Kaiser Wilhelm-Platz 1, 45470 Mülheim a. d. R. e-mail: [email protected]

Lythranidine (1) is a cylcophane alkaloid which was isolated in 1967 by Fujita and

co-workers from the Japanese plant Lythrum anceps Makino together with two related natural products.1 It features a 17-membered ring fused to a trans-2,6-disubstituted piperidine ring. Retrosynthetically, this motif could be constructed by a ring-closing alkyne metathesis (RCAM) of diyne 3 followed by an E-selective redox isomerization of the propargylic alcohol to the corresponding enone and subsequent aza-Michael addition.

MeO OH

OH

PG''HN

PG'O

MeO OH

OH HOHN

H H

Lythranidine (1)

MeO OH

PG'O PG''N

H H

O

aza-Michael addition

Ring-closing alkyne metathesis

+ redox isomerization

2 3 Scheme 1. Retrosynthetic analysis of (1), PG = protecting group.

Herein, the first enantioselective total synthesis of lythranidine (1) is presented. It features a longest linear sequence of 15 steps and applies the outlined synthetic key transformations in good to excellent yields.

[1] E. Fujita,; K. Fuji, K. Bessho, A. Sumi, S. Nakamura, Tetrahedron Lett. 1967, 46, 4595-4600.

38

Poster 12

Nickel-Catalyzed Amination of Aryl Chlorides Rebecca A. Green, Shaozhong Ge, John F. Hartwig*

Department of Chemistry, University of California, Berkeley, California, 94720, USA e-mail: [email protected], [email protected]

Transition-metal catalyzed amination of aryl halides has become a useful alternative

to classic methods for the synthesis of arylamines. However, the majority of these reactions have been conducted with expensive palladium catalysts or less reactive copper catalysts. A few nickel-catalyzed amination reactions have been reported, but the scope of amines that undergo this transformation is limited to secondary alkylamines and anilines. To overcome these limitations, we have developed a single-component nickel precursor that catalyzes the amination of aryl and heteroaryl chlorides with primary alkyl amines. In-depth mechanistic and kinetic studies suggest that oxidative addition of aryl chloride to a coordinatively unsaturated Ni(0) species is the turnover-limiting step of the Ni(0)/Ni(II) catalytic cycle. 1 In addition, we have developed, for the first time, a nickel-catalyzed amination of aryl chlorides with ammonia to produce anilines. The single-component nickel precatalysts for these amination reactions are ligated by bisphosphines and an η2-bound benzonitrile, which promotes a rapid oxidative addition of aryl chlorides.

[1] S. Ge, R. A. Green, J. F. Hartwig, J. Am. Chem. Soc. 2014, 136, 1617.

39

Poster 13

Selective Metalation and Functionalization of Oxazoles and Oxazolines Using 2,2,6,6-Tetramethylpiperidyl Bases

Diana Haas,a Marc Mosrin,b Paul Knochel*a

aLudwig-Maximilians-Universität München, Department Chemie, Butenandtstr. 5-13, Haus F, 81377

München, Germany bBayer CropScience AG, Industriepark Höchst, 65926 Frankfurt am Main


The selective functionalization of sensitive heterocycles, such as oxazoles and

oxazolines, is still a topic of growing interest. Direct metalation has already shown to be an excellent tool for this purpose. Sterically hindered TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl) of Mg1 and Zn2 have proven to be especially efficient for a broad range of metalations particularly for sensitive heterocycles. Thus, a complete and controlled functionalization of the oxazole scaffold is achieved by successive metalation reactions with TMPZnCl·LiCl.3

NO

1) TMPZnCl·LiCl 0 °C, 1 h NO NO

NO

2) 1-chloro-4-iodobenzene 3% Pd(dba)2 6% P(o-furyl)3 50 °C, 2 h

1) TMPZnCl·LiCl 50 °C, 2 h

2) 4-fluorobenzoyl chloride 4% Pd(PPh3)4 25 °C, 4 h

1) TMPZnCl·LiCl 50 °C, 3 h

2) CuCN·2LiCl 25 °C, 0.5 h3) 3-bromocyclohexene 25 °C, 2 hCl

Cl Cl

O

F

O

F

83% 86% 74%

Furthermore, 4,4-dimethyloxazoline was metalated, subsequently used in Negishi cross-couplings with various aryl halides and then utilized as a directing group for the metalation of the previously introduced aromatics. This provides an easy access to substituted benzoic acids after deprotection of the oxazoline moiety.4

[1] A. Krasovsky, V. Krasovskaya, P. Knochel, Angew. Chem., Int. Ed. 2006, 45, 2958-2961.

[2] M. Mosrin, P. Knochel, Org. Lett. 2009, 11, 1837-1840. [3] D. Haas, M. Mosrin, P. Knochel, Org. Lett. 2013, 15, 6162-6165.

[4] A. I. Meyers, E. D. Mihelich, Angew. Chem. Int. Ed. 1976, 15, 270-281.

40

Poster 14

Two Gold Centers Applied in Organic Synthesis: Dual Activation of Diynes Max M. Hansmann, A. Stephen K. Hashmi*

Organisch-Chemisches Institut, Ruprecht-Karls Universität Heidelberg Im Neuenheimer Feld 270, 69120 Heidelberg, Germany


In the last decade homogenous gold catalysis has become an important tool for organic synthesis. Very recently, our group could demonstrate a new type of σ,π-dual-activation utilising diyne systems.1 Herein one gold center activates one alkyne via π-coordination while the other reacts as σ-gold-acetylide to generate gold-vinylidenes – a new class of highly reactive intermediates. In the current work we highlight a new bifurcation pathway in the dual gold-catalysed cyclisation of diynes which leads to the unprecedented 6-endo-cyclisation event generating gold-stabilised carbenes. 2 These new intermediates undergo selective C(sp3)-H activation of unactivated alkyl chains affording indane derived products.

[Au]

[Au]+ R

dual-activation

R

[Au]

+[Au]

[Au]

[Au]+

R

5-endo-dig

vinylidenepathway

carbenepathway

6-endo-dig

bifurcation

products

products

[1] A. S. K. Hashmi, I. Braun, P. Nösel, J. Schädlich, M. Wieteck, M. Rudolph, F. Rominger, Angew.

Chem. Int. Ed. 2012, 51, 4456-4460; A. S. K. Hashmi, M. Wieteck, I. Braun, M. Rudolph, F.

Rominger, Angew. Chem. Int. Ed. 2012, 51, 10633-10637.

[2] M. M. Hansmann, M. Rudolph, F. Rominger, A. S. K. Hashmi, Angew. Chem. Int. Ed. 2013, 52, 2593-2598; M. M. Hansmann, S. Tsupova, M. Rudolph, F. Rominger, A. S. K. Hashmi, Chem. Eur.

J. 2014, DOI: 10.1002/chem.201302967.

41

Poster 15

General Allylic C-H Alkylation with Tertiary Nucleophiles Jennifer M. Howell, Wei Liu, Andrew J. Young, M. Christina White*

Department of Chemistry, University of Illinois, Urbana, Illinois, 61801, USA e-mail: [email protected]

Palladium(II)/bis(sulfoxide) catalysis has enabled a general strategy for

intermolecular allylic C-H alkylation of terminal olefins, previously with secondary carbon nucleophiles1 and now with tertiary carbon nucleophiles. The olefin scope includes aliphatic, aromatic, heteroaromatic olefins and 1,4-dienes. The mild and selective nature of this allylic C-H alkylation coupled with the ease of appending allyl moieties onto complex scaffolds permits rapid diversification of phenolic natural products. A broad range of tertiary nucleophiles proved competent for functionalization, many containing latent functionality (e.g. aliphatic alcohols, α,β-unsaturated ketones). The generality of this C-H reactivity facilitates synthetic streamlining, as is illustrated in a tandem allylic C-H alkylation/Diels-Alder cascade that rapidly furnishes a common tricyclic core found in the class I galbulimima alkaloids from simple acyclic precursors.

[1] a) A. J. Young, M. C. White, J. Am. Chem. Soc. 2008, 130, 14090; b) S. Lin, C. X. Song, G. X. Cai, W. H. Wang, Z. J. Shi, J. Am. Chem. Soc. 2008, 130, 12901; c) A. J. Young, M. C. White, Angew. Chem. Int. Ed. 2011, 50, 6824.

42

Poster 16

Salt Formation Strategy for Asymmetric Hydrogenation of N-Heteroaromatic Compounds

Atsuhiro Iimuro, Kenta Yamaji, Shoji Hida, Yusuke Kita, Kazushi Mashima*

Department of Chemistry, Graduated School of Engineering Science, Osaka University, Toyonaka, Osaka

560-8531, Japan


Chiral cyclic amines are highly important molecular skeletons abundant in natural

alkaloids as well as biologically active compounds. Catalytic asymmetric hydrogenation of N-heteroaromatic compounds has been considered as one of the most straightforward routes. Due to its aromatic nature, catalytic hydrogenations of isoquinolines and pyridines have been regarded as difficult tasks so far. In the course of our investigation, we found that the salt formation of the substrates facilitated asymmetric hydrogenation of isoquinolines with high enantioselectivity. 1 This strategy was also applied to asymmetric hydrogenation of pyridines.2 In these reactions, multi-substituted substrates were smoothly hydrogenated to afford the corresponding chiral cyclic amines with high diastereoselectivity.

[1] A. Iimuro, K. Yamaji, S. Kandula, T. Nagano, Y. Kita, K. Mashima, Angew. Chem. Int. Ed. 2013, 52, 2046-2050.

[2] Y. Kita, A. Iimuro, S. Hida, K. Mashima, Chem. Lett. 2014, in press.

43

Poster 17

Catalytic Formation of Sodium Acrylate from CO2 and Ethylene Núria Huguet,a Ivana Jevtovikj,a Chantal Stieber,a Andrey Khalimon,a Miriam Bru,a

Alvaro Gordillo,a Piyal Ariyananda,a Philipp-Nikolaus Plessow,a,b Michael Limbach*a,c aCaRLa – Catalysis Research Laboratory, Im Neuenheimer Feld 584, D-69120 Heidelberg, Germany;

bOrganisch-Chemisches Institut Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany; cBASF SE, Synthesis and Homogeneous Catalysis, GCS/C – M313, Carl-

Bosch-Strasse 38, D-67056 Ludwigshafen, Germany e-mail: [email protected]

For more than three decades the catalytic synthesis of acrylates from the cheap and abundantly available C1 building block CO2 and alkenes has been an unsolved problem in catalysis research, both in academia and industry. Sodium acrylate is an important basic chemical that serves as a monomer for the synthesis of superabsorbent polymers. The current industrial process is based on a two-step oxidation of propylene. The catalytic synthesis of acrylates from CO2 and ethylene is considered to be a dream reaction.

CO2

ONa

O

R1OH

Ni(COD)2

PR2R2P

dtbpe

PNi

P ONa

O

PNi

P

R2

R2

R2

R2

PNi

PR2

R2O O

NaOR1

PNi

PR2

R2O ONa

OR1

Nickelalactones, as reported in the early work of Hoberg,1 have been discussed as a possible entry to a catalytic cycle. The first homogeneous catalyst system ever based on a Ni-complex is presented. It allows the clearly catalytic synthesis of Na-acrylate from CO2, ethylene and a base, as demonstrated by a TON of 10 at this stage.2

[1] H. Hoberg, Y. Peres, C. Krüger, Y. H. Tsay, Angew. Chem. Int. Ed. 1987, 26, 771-773. [2] M. Lejkowski, R. Lindner, T. Kageyama, G. E. Bódizs, P. N. Plessow, I. B. Müller, A. Schäfer, F.

Rominger, P. Hofmann, C. Futter, S. A. Schunk, M. Limbach, Chem. Eur. J. 2012, 18, 14017-14025.

44

Poster 18

Development of Cationic Ruthenium Carbene Complexes Incorporating Bidentate NHCP Ligands

Phillip Jolly,a Kristina Wilckens,a Hiyam Salem,a Martin Schmitt,b Frank Rominger,b Peter Hofmann*a,b

aCatalysis Research Laboratory (CaRLa), University of Heidelberg, Im Neuenheimer Feld 584, D-69120

Heidelberg, Germany bOrganisch-Chemisches Institut, University of Heidelberg, Im Neuenheimer Feld 270, D-69120

Heidelberg, Germany

Well defined, active and durable catalysts have revolutionized the field of olefin metathesis. In previous work, Hofmann and co-workers reported cationic ruthenium carbene complexes stabilized by cis-chelating bulky and electron-rich bisphosphine ligands. The “cis-Hofmann I” catalysts are analogous to the active complex of a trans-Grubbs 1st generation catalysts and exhibit exceptional activity in ROMP even at ppm-range catalyst concentrations.1

In light of the advantages which NHCs confer to Grubbs 2nd generation catalysts, bidentate NHC-Phosphine ligands (NHCPs) have been employed to synthesis cationic ruthenium carbene “cis-Hofmann II” complexes. Catalyst synthesis and preliminary screening are described.2

RuP

NHCR1

tBu2

trans-Grubbs I

RuCl

Cl

tBu2P

PtBu2

R1

DCM, rtTMSOTf

Ru Cl

tBu2P

PtBu2

R1

RuCl

PCy3Cl

Cy3P

R1 OTf

RuP Cl

NHC ClR1

tBu2

RuCy3P Cl

Cl NHCR1

trans-Grubbs II

RuP

NHC ClR1

tBu2

DCM, rtTMSOTf

Active 14 VE cis-Hofmann II

Active 14 VE cis-Hofmann I

OTf

Ru

tBu2P

PtBu2

R1

RuCl

Cl

tBu2P

PtBu2

R1

2OTf2

RuP Cl

NHC ClR1

tBu2

2OTf2

[1] M. A. O. Volland, S. M. Hansen, F. Rominger, P. Hofmann, Organometallics 2004, 23, 800. [2] H. Salem, M. Schmitt, U. Herrlich, E. Kühnel, M. Brill, P. Nägele, A. L. Bogado, F. Rominger, P.

Hofmann, Organometallics 2013, 32, 29.

45

Poster 19

Palladium and Nickel Catalyzed C-H Arylations Kalyani Dipannita*

St. Olaf College e-mail: [email protected]

The discovery of novel transition metal-catalyzed methods for the direct conversion of C-H to C-C bonds remains an important challenge in organic chemistry. The vast majority of previous literature reports have accomplished such transformations using aryl halides as electrophiles.1 Recently, there has been an increasing interest toward the use of phenolic electrophiles in place of aryl halides.2 Our preliminary efforts toward contributing to this goal will be presented.

Palladium-catalyzed inter- and intramolecular C-H arylation is accomplished using inexpensive and readily available tosylates and mesylates as electrophiles. 3 This transformation is efficient for the synthesis of various heterocyclic motifs including furans, carbazoles, indoles, and lactams. The use of earth-abundant and inexpensive nickel catalysts for an intramolecular C-H arylation using aryl pivalates as electrophiles will be described.4 Preliminary mechanistic investigations for these C-H arylations will be discussed.

These studies will contribute toward broadening the scope of the metal-catalyzed C-C bond constructions using phenolic electrophiles.

[1] D. Alberico, M. E. Scott, M. Lautens, Chem. Rev. 2007, 107, 174-238. [2] B. M. Rosen, K. W. Quasdorf, D. A. Wilson, N. Zhang, A.-M. Resmerita, N. K. Garg, V. Percec,

Chem. Rev. 2011, 111, 1346-1416. [3] C. S. Nervig, P. J. Waller, D. Kalyani, Org. Lett. 2012, 14, 4838-4841.

[4] J. Wang, D. M. Ferguson, D. Kalyani, Tetrahedron 2013, 5780-5790.

46

Poster 20

Enantioselective Rh-Catalyzed Coupling of Carboxylic Acids with Terminal Alkynes and Allenes

Philipp Koschker, Bernhard Breit*

Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21,

79104 Freiburg im Breisgau, Germany.


Branched allylic esters are versatile intermediates for the construction of complex

molecules. While many methods for their synthesis are known,1 they are limited by the need for stoichiometric reagents, low yields and/or low selectivities.

Therefore we developed a new approach to form these compounds through an atom-economic and highly selective reaction starting from terminal alkynes. Furthermore we found an asymmetric variant of this methodology starting directly from the corresponding allene substrate.2

DPEphosup to 91% yieldup to >98:2 B:M selectivity

Ph2PO

PPh2H

R1[Rh(COD)Cl]2 (2.5 mol%),

DPEphos (5.0 mol%),DCE, 70°C, 16h R1

O

O

R2

R2HO

O

[Rh(COD)Cl]2 (4.5 mol%),

(R,R)-DIOP (9.0 mol%),Cs2CO3 (9.0 mol%),0.1 M in DCE, 48h

+R2HO

O

R1

up to 98% yieldup to 96% ee

R1 = Alkyl, CxNR2, CxOH, CxOR,...R2 = Alkyl, Aryl, Heteroaryl, Alkenyl,...

R1

H(R')H(R')O

R2

O O

O

(R,R)-DIOP

PPh2

PPh2

[1] D. M. Hodgson, P. G. Humphreys, Science of Synthesis: Houben-Weyl Methods of Molecular

Transformations; J. P. Clayden, Ed.; Thieme, Stuttgart, Germany, 2007; Vol. 36, pp 583-665. [2] A. Lumbroso, P. Koschker, N. R. Vautravers, B. Breit, J. Am. Chem. Soc. 2011, 133, 2386; P.

Koschker, A. Lumbroso, B. Breit, J. Am. Chem. Soc. 2011, 133, 20746.

47

Poster 21

Asymmetric Catalysis on the Nanoscale: The Organocatalytic Approach to Helicenes

Lisa Kötzner, Matthew J. Webber, Alberto Martínez, Claudia De Fusco, Benjamin List* Max-Planck-Institut für Kohlenforschung

Kaiser Wilhelm-Platz 1, 45470 Mülheim an der Ruhr


Helically chiral molecules have recently attracted enormous attention in fields such as catalysis or materials science. To date, catalytic asymmetric syntheses have mainly been achieved via transition metal catalysis. 1 Herein, we report the asymmetric organocatalytic synthesis of helicenes, applying the enantioselective Fischer indolization.2 The methodology is based on a long-range control by the catalyst, whose extended π-substituents could engage in a π-π stacking interaction with the polyaromatic system in the intermediate. A variety of azahelicenes and bis-azahelicenes could be obtained with good to excellent yields and enantioselectivities.

NNH2

R2

O NR2

R1

R3R1

R3

10 examplesup to 98% yield

er up to 96:4

+ POHO

O O

[1] For a review see: Y. Shen, C.-F. Chen, Chem. Rev. 2012, 112, 1463-1535.

[2] a) S. Müller, M. J. Webber, B. List, J. Am. Chem. Soc. 2011, 133, 18534-18537; b) A. Martínez, N. J. Webber, S. Müller, B. List, Angew. Chem. Int. Ed. 2013, 52, 9486-9490; c) L. Kötzner, M. J. Webber, A. Martínez, C. De Fusco, B. List, manuscript submitted.

48

Poster 22

Alkali Metal Silyl Catalyzed Hydrosilylation of C-C Double Bonds: A Mechanistic Insight

Valeri Leich, Thomas P. Spaniol, Jun Okuda*Institute of Inorganic Chemistry, RWTH Aachen University, Landoltweg 1, Aachen, 52074, Germany


Catalytic hydrosilylation of alkenes is a commercially utilized process for the efficient synthesis of organosilicon compounds.1 Potent catalysts such as Speier2 and Karsted3 catalysts are based on late transition metals. Recently, attention has shifted to more inexpensive alternatives based on main group metals including AlCl3 and B(C6F5)3.4 The first series of well-defined catalysts based on s-block metals (K, Ca. Sr), with presumably a metal hydride as catalytically active species, was introduced by Harder et al..5 A metal silyl was also implicated as active species in the hydrosilylation of C–C double bonds. Although used in synthetic chemistry,6 metal silyls have never been applied as hydrosilylation catalysts before.

A series of new alkali metal triphenylsilyls [M(crown-ether)SiPh3(thf)] (M = Li(12-crown-4), Na(15-crown-5), K(18-crown-6)) were synthesized, fully characterized and successfully applied in the hydrosilylation of olefins. Isolation, characterization and in situ NMR spectroscopy studies of intermediates led to the conclusion, that silyl instead of a hydride mechanism is operative.

[1] B. Marciniec, Coord. Chem. Rev. 2005, 249, 2374-2390.

[2] J. L. Speier, Adv. Organomet. Chem. 1979, 17, 407-447. [3] a) B. D. Karsted, U. S. Patent 3 715 334, 1973; b) B. D. Karsted, US-A 3 775 452, 1973; c) P. B.

Hitchcock. M. F. Lappert, N. J. W. Warhurst, Angew. Chem. Int. Ed. Engl. 1991, 30, 438-440. [4] a) K. Oertle, H. Wetter, Tetrahedron Lett. 1985, 26, 5511-5514; b) M. Rubin, T. Schwier, V. J.

Gevorgyan, J. Org. Chem. 2002, 67, 1936-1940.

[5] S. Harder, J. Brettar, Angew. Chem. Int. Ed. 2006, 45, 3474-3478.

[6] a) K. Tamao, A. Kawachi, Adv. Organomet. Chem. 1995, 30, 1-58; b) P. D. Lickiss, C. M. Smith, Coord. Chem. Rev. 1995, 145, 75-124; c) A. Sekiguchi, V. Y. Lee, M. Nanjo, Coord. Chem. Rev. 2000, 210, 11-45.

49


Poster 23

Ligand effects in the rhodium nanoparticles catalysed selective hydrogenation Jessica Llop, Carmen Claver, Cyril Godard*

Departament Química Física i Inorgànica, Universitat Rovira i Virgili, C/Marcel·lí Domingo s/n 43007 Tarragona


In the last decade, P-based ligands were shown to efficiently stabilise metal nanoparticles that are catalysts in several catalytic reactions.1 However, to date, the fine tuning of the properties of this type of catalysts to achieve specific selectivities remains a challenge. Recently, our research group reported the synthesis of M-NPs stabilised by phosphite ligands and their application in the catalytic hydrogenation of arenes, obtaining high activities and selectivities.2 Part of these results were recently reported.3 Here, we describe the synthesis and characterisation of Rh-NPs stabilised by several types of phosphorus based ligands and their application in chemoselective hydrogenation reactions. The effects of the nature and properties of the ligands on the structure and catalytical behavior of the NPs are included.

[1] A. Roucoux, J. Schulz, H. Patin, Chem. Rev. 2002, 102, 3757; D. Astruc, F. Lu, J. R. Aranzaes, Angew. Chem. Int. Ed. 2005, 44, 7852.

[2] A. Gual, C. Godard, S. Castillon, C. Claver, Dalton Trans. 2010, 39, 11499; A. Gual, C. Godard, K. Philippot, B. Chaudret, A. Denicourt-Nowicki, A. Roucoux, S. Castillón, C. Claver,

ChemSusChem 2009, 2, 769. [3] J. Llop Castelbou, A. Gual, E. Mercadé, C. Claver, C. Godard, Catal. Sci. Technol. 2013, 13,

2828-2833.

50


Poster 24

Alkane Dehydrogenation Using Ethylene as the Hydrogen Acceptor Thomas W. Lyons, Maurice Brookhart*

University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA e-mail: [email protected]

As oil supplies diminish, new routes to chemical intermediates that utilize alternative

feedstocks will be needed. Aromatics constitute one important class of chemicals currently derived from crude oil. BTX (benzene, toluene, and xylenes) is currently produced by dehydrogenating petroleum fractions using a heterogeneous reforming catalyst at high temperatures (> 500 ºC). We previously reported the conversion of linear alkanes to aromatics under much more mild conditions by using iridium pincer catalysts and 4 equivalents of an acceptor olefin, tert-butylethylene (TBE).1 The use of relatively expensive TBE however, has limited the practicality of this process. Building on this work, we recently reported the use of an anthraphos-based iridium catalyst with ethylene as the hydrogen acceptor as part of a selective synthesis of p-xylene using ethylene as the sole feedstock.2 Ethylene represents an attractive hydrogen acceptor because it is inexpensive, readily abundant, and can potentially be derived from alternative feedstocks (ethanol). The ethane produced from this reaction can be readily cracked back to ethylene. Herein we describe our efforts to expand this chemistry to other important building blocks.

[1] R. Ahuja, B. Punji, M. Findlater, C. Supplee, W. Schinski, M. Brookhart, A. S. Goldman, Nat. Chem. 2011, 3, 167.

[2] T. W. Lyons, D. Guirronnet, M. Findlater, M. Brookhart, J. Am. Chem. Soc. 2012, 134, 15708.

51

Poster 25

Rhodium-Catalysed Bis-Hydroformylation of 1,3-Butadiene to Adipic Aldehyde Jaroslaw Mormul,a Michael Mulzer,a Eszter Takács,a Stuart E. Smith,a Michael

Limbach,a Peter Hofmann*a,b aCatalysis Research Laboratory (CaRLa), Im Neuenheimer Feld 584, D-69120, Heidelberg,

Germany bOrganisch-Chemisches Institut, University of Heidelberg, Im Neuenheimer Feld 270, D-69120

Heidelberg, Germany


Hydroformylation (the “oxo reaction”) is one of the largest homogeneous transition-metal-catalysed processes operated industrially.1,2 Despite the importance and atom economy of the oxo process, the dihydroformylation of conjugated dienes is not a standard reaction.1 For instance, the simplest diene, 1,3-butadiene, typically obtained from large industrial steam-cracking units, can yield up to 14 different aldehydes and their reaction products.

O OP P

O

O

O

O

Me

MeMe

Me

Me

MeMe

Me

[Rh]+ 2H2 + 2CO H

HO

O

50% selectivity

Different reaction conditions and new ligand structures have been examined in the rhodium-catalysed low-pressure hydroformylation of 1,3-butadiene. The selectivity for the desired linear dihydroformylation product, 1,6-hexanedial (adipic aldehyde), is essentially less dependent of all reaction parameters, than for ligand structure variation. The optimum reaction parameters and ligand structures have so far resulted in a maximum selectivity of 50% for adipic aldehyde.3

[1] H.-J. Arpe, Industrial Organic Chemistry, 5th ed.; Wiley-VCH: Weinheim, Germany, 2010.

[2] P. W. van Leeuwen, C. Claver, (Eds.) Rhodium Catalyzed Hydroformylation (Catalysis by Metal Complexes); Kluwer, Dordrecht, 2000.

[3] S. E. Smith, T. Rosendahl, P. Hofmann, Organometallics 2011, 30, 3643-3651.

52

Poster 26

Reactive intermediates for stereoselectively constructing tetrahydrofurans from cobalt(III)-superoxo-activated 4-pentenols

Melanie Kim Müller, Jens Hartung*TU Kaiserslautern, Erwin-Schrödinger-Str. 54, 67663 Kaiserslautern, Germany


Oxidation of 4-pentenols (bishomoallylic alcohols) by cobalt-activated dioxygen in solutions of cyclohexa-1,4-diene (CHD) affords constitutionally dissymmetric tetrahydrofurans.1 The products are formed in a two-step mechanism, composed of cobalt-catalyzed regio- and stereoselective oxidative alkenol cyclization, and trapping of tetrahydrofuryl-2-methyl radicals by H- or Br-atom donors, alkenes, alkines or disulfides for synthesis of functionalized cyclic ethers.2,3 While methods for selectively trapping the tetrahydrofuryl-2-methyl radical are developed to a considerable extend, nothing is known so far on the mechanism of the C,O bond forming.

HL = e.g., ß-diketone

OH

L2Co

RX / H2O

H2X / O2

L2Co•

III

OHO CH2

O2H O2

L2CoII O2

III

R

R

•

•O CH2R

For approaching the quest for the chemical nature of the selectivity determing intermediate we pursue a combined physical organic and synthetic study. Results of this study will be reported and discussed.

[1] P. Fries, M. K. Müller, J. Hartung, Org. Biomol. Chem. 2013, 11, 2630-2637. [2] P. Fries, D. Halter, A. Kleinschek, J. Hartung, J. Am. Chem. Soc. 2011, 133, 3906-3912.

[3] B. Menéndez Peréz, D. Schuch, J. Hartung, Org. Biomol. Chem. 2008, 6, 3532-3541.

53

Poster 27

Iron-Catalyzed Diboration and Carboboration of Alkynes Naohisa Nakagawa, Takuji Hatakeyama, Masaharu Nakamura*

International Research Center for Elements Science (IRCELS), Institute for Chemical Research (ICR), Kyoto University, Uji, Kyoto, 611-0011, Japan.

e-mail: [email protected], [email protected]

With the development of Suzuki-Miyaura cross-coupling reaction, focus has fallen

on alkenylboron compounds as key intermediates for the synthesis of a wide range of functional molecules, such as electronic materials and bioacitve natural products. Diborylalkenes are particularly attractive building blocks for substituted alkenes or π-extended conjugated polyarenes, and their expedient synthesis has attracted considerable attention from synthetic chemists. Transition-metal-catalyzed diboration of alkynes have thus far been investigated intensively and extensively;1 a variety of transition metals, such as platinum, cobalt, iridium, copper, and gold can catalyze the diboration of alkynes to give diboryl alkenes. We have found that a simple iron salt can catalyze the diboration of alkynes in a highly stereoselective and efficient manner. In addition, the present catalyst system is amenable to in situ trapping with unactivated alkyl halides to furnish a wide array of alkenyl boron compounds as a single geometrical isomer.

[1] Recent review: J. Takaya, N. Iwasawa, ACS. Catal. 2012, 2, 1993-2006.

54

Poster 28

Copolymerization of Carbon Dioxide and Dienes via Lactone Intermediate Ryo Nakano, Shingo Ito, Kyoko Nozaki*

Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan


While carbon dioxide has attracted broad interest as a renewable C1 feedstock, its use as a monomer in copolymerization with olefins has long been an elusive endeavor. A major obstacle for this process is the endothermic propagation step involving carbon dioxide.

In this study, we established a new strategy to circumvent kinetic and thermodynamic barriers for copolymerization of carbon dioxide and olefins by using a meta-stable lactone intermediate, 3-ethylidene-6-vinyl-tetrahydro 2H-pyran-2-one (1), which is formed by the palladium-catalyzed condensation of carbon dioxide and 1,3-butadiene. Subsequent free radical polymerization of 1 afforded high-molecular-weight polymers with a carbon dioxide content of 33 mol% (29 wt%). The poly-1 obtained in the presence of acetic acid only possessed bicyclic structure α (upper, Mn = 19,000). On the other hand, zinc chloride/ ethylene carbonate conditions gave a polymer with unit α, β, and γ (lower, Mn = 85,000).

1

V-40

AcOH100 °C, 24 h

OO

Me

α β γ

OO

MeO

O

MeO

O

Me

n

α

OO

Me

n

V-40ZnCl2

100 °C, 24 h

+[Pd]

CO2

O

OO

Furthermore, the protocol was successfully applied to one-pot copolymerization of carbon dioxide and 1,3-butadiene, and one-pot terpolymerization of carbon dioxide, butadiene, and another 1,3-diene.

55

Poster 29

Carbene Transfer in Gold Catalysis Pascal Nösel, A. Stephen K. Hashmi*

Institute of Organic Chemistry, Ruprecht-Karls University of Heidelberg, Germany, Im Neuenheimer Felder 271, 69120 Heidelberg


In the presence of a gold catalyst and an N-oxide an unprecedented oxidative cyclization of diynes takes place.1,2 The reaction cascade is initiated by creation of an α-oxo carbene which is subsequently transferred to the second alkyne, furnishing a stabilized vinyl carbene/cation. Alkyl migration or sp3-CH insertion leads to the formation of highly substituted, functionalized indenones. This protocol represents an alternative to procedures which are based on the metal-catalyzed decomposition of hazardous, not easily accessible, diazo compounds.

R O

RR RN

O

R

[Au]

Carbene Transfer

O

RRAlkyl-Migration

CH-Insertion

O

R = Halogen, Ph

R = t-Bu[Au]

R

[1] P. Nösel, L. N. dos Santos Comprido, T. Lauterbach, M. Rudolph, F. Rominger, A. S. K. Hashmi, J.

Am. Chem. Soc. 2013, 135, 15662. [2] P. Nösel, T. Lauterbach, M. Rudolph, F. Rominger, A. S. K. Hashmi, Chem. Eur. J. 2013, 19,

8634-8641.

56

Poster 30

A Cooperative Iridium-bisMETAMORPhos Complex for the Dehydrogenation of Formic Acid

S. Oldenhof, B. de Bruin, J. I. van der Vlugt, J. N. H. Reek*van ’t Hoff Institute for Molecular Sciences, University of Amsterdam, The Netherlands


Hydrogen holds the potential to be one of the major energy carriers for the future. However, a hydrogen-based economy requires technology that allows efficient and safe storage and release of H2. In this light, the reversible storage of hydrogen in the form of formic acid provides an interesting H2 storage-release system. Substantial developments in the production of formic acid since the early nineties have stimulated interest in the reverse reaction for hydrogen release on demand. Ideally, catalytic dehydrogenation takes place in the absence of base and additives, thereby maximizing the overall hydrogen storage capacity and preventing hydrogen contamination with traces of volatile amines that may poison the fuel cell. We envisioned ligand cooperativity could provide an interesting approach in this area as metal complexes with an internal base as part of the ligand could be developed. In this contribution we present a novel iridium-bis- METAMORPhos complex that is active in formic acid dehydrogenation in the absence of external base, and demonstrate that the ligand plays an active role in the mechanism by pre-assembling formic acid, stabilizing the transition state and the deprotonation of formic acid (see figure).

57

Poster 31

Heterocyclic Compounds via Asymmetric Organocatalytic One-pot Strategies Lars Krogager Ransborg, Karl Anker Jørgensen*

Center for Catalysis, Department of Chemistry, Aarhus University, Denmark


Organocatalysis has been established as one of the three fundamental methods for catalytic formation of optically active compounds. Currently, the development of one-pot reaction cascades is one of the main focus areas within the field. Recently, we have focused on the construction of chiral heteroaromatic motifs, which hold a prominent position in natural as well as synthetically obtained molecules. This poster outlines the results that have been obtained in our group during these studies.

NH

Ar

Ar

OTMS

OR1

H2O2 or TsNHOTs

R2

OOH

NHBn

R1

X = O, NTs

or

R2

O OH

R1

HO

N

Y

R2

R1

XH

OR3

O

R2

R1

XH

N

YR2R1

XHY = NH, O, S

YN

EWG

R1

XH

R2

R3

H

H

Y = N, CCOOEt

Y = S, Se

Ar = 3,5-(CF3)2-C6H3-

58

Poster 32

Chiral Ditopic Cyclophosphazane Ligands: Synthesis, Coordination Chemistry and Application in Asymmetric Catalysis

T. Roth,a H. Wadepohl,a D. S. Wright,b L. H. Gade*a

aRuprecht-Karls-Universität, INF 270, 69120 Heidelberg (Germany); bCambridge

University, Lensfield Rd, Cambridge CB2 1EW (UK).


Two decades ago the groups of Alexakis, Feringa, Reetz and Pringle successfully challenged the conventional wisdom of the superior enantioselectivity of bidentate chiral catalysts by introducing monodentate phosphorus based ligands to asymmetric catalysis.1 They obtained activities and selectivities comparable to those of the established C2-symmetric ligand scaffolds. The main advantages of these new ligand arrangements is their robustness as well as the ease by which they can be prepared and their steric and electronic demands elaborated.

Here, we present the synthesis of a series of novel chiral exo-bidentate binol-bridged cyclophosphazane ligands, a systematic study of their coordination to late transition metals and an investigation of their activity in the AuI-catalyzed hydroamination of allenes and the Ni0-catalyzed coupling of 1,3-dienes and aldehydes.2

PCl3 + RNH2 P

NPN

Cl Cl

R

R

R'

R'

OO

P

PNNR R

MLn

R'

R'

OO

P

PNNR R

MLn-1

MLn-1

[1] Selected Reviews: a) J. F. Teichert, B. L. Feringa, Angew. Chem. Int. Ed. 2010, 49,

2486; b) I. V. Komarov, A. Börner, Angew. Chem. Int. Ed. 2001, 40, 1197.

[2] T. Roth, H. Wadepohl, D. S. Wright, L. H. Gade, Chem. Eur. J. 2013, 19, 13823.

59

Poster 33

Rapid Assessment of Protecting-Group Stability by Using a Robustness ScreenAndreas Rühling, Karl D. Collins, Fabian Lied, Frank Glorius* Westfälische Wilhelms-Universität Münster, Organisch-Chemisches Institut


In contrast to the rapid publication of scientific information, the application of new knowledge is often still slow, and we believe this to be particularly true of newly developed synthetic organic chemistry methodology. Consequently, methods to assess and identify robust chemical reactions are desirable, and would directly facilitate the application of newly reported synthetic methodology to complex synthetic problems. We recently developed a simple process for assessing the likely scope and limitations of a chemical reaction beyond the idealized reaction conditions initially reported.1,2

Our approach is conceptually very simple, and provides data that is complementary to that obtained in the substrate scope: A standard reaction is undertaken in the presence of one molar equivalent of an additive for a given chemical functionality or structural motif. Reactions are analysed using gas chromatography (GC), providing a quantitative assessment of the yield of the reaction and the amount of additive remaining, and thus determining the tolerance of the reaction to the given additive, and of the stability of the additive to the reaction conditions.

A Robustness Screen

x

tolerance of/to additives

A B

Representative Additives:

RR Cl

N

OR

NS

RC

NCl-

More recently we have extended this methodology to the important field of protecting group chemistry, a fundamental aspect of the synthesis of complex organic molecules. When designing synthetic routes the selection of appropriate protecting

[1] K. D. Collins, F. Glorius Nature Chem. 2013, 5, 597. [2] K. D. Collins, A. Rühling, F. Glorius, Nat. Protoc. 2014, accepted.

60

Poster 33

groups is critical, and requires knowledge of both the protecting groups, and the reaction conditions to which they will be exposed. Using the Cu(OAc)2-mediated synthesis of pyrazoles,3 we individually assessed the stability of these protecting groups to the reaction conditions. We were also able to demonstrate multiple protecting groups can be simultaneously assessed in a single experiment, enhancing the practicability of our protocol.4 Furthermore we validated the results using complex molecules containing protecting groups in the pyrazole synthesis, and importantly in an unrelated transformation.

pyrazole

A Robustness Screen

Stability of/to Protecting Groups

synthesis

x

- OSi

nPr nPrOO

Ph

HN O

OtBu

Representative Protecting Groups:

BA

PG PG

nPr

S

S

[3] M. Suri, T. Jousseaume, J. J. Neumann, F. Glorius, Green Chem. 2012, 14, 2193. [4] K. D. Collins, A. Rühling, F. Lied, F. Glorius, Chem. Eur. J. 2014, DOI:

10.1002/chem.201304508.

61

Poster 34

From Frustrated Lewis Pairs to a New Class of Persistent Free Radicals and Use of CO as C1 Source

Muhammad Sajid, Gerald Kehr, Gerhard Erker*Organisch-Chemisches Institut, Westfälische-Wilhelms Universität, Corrensstr. 40, 48149 Münster,

Germany


Frustrated Lewis Pair (FLP) chemistry is an emerging field and is recently gaining tremendous attentation.1 Metal free catalytic hydrogenation is one of the most interesting and promising aspects of FLPs. We have recently shown that FLPs can trap NO gas to give rise to a new class of persistent nitroxide free radicals.2 We explored different reactions of these free radicals and used their alkoxyamine derivatives for controlled (nitroxide mediated) polymerization of styrene.

Recently we could show the reduction of carbon monoxide on the intramolecular FLP templates.3 The resulting compounds of this reaction were used to generate a novel formylborane.4 The reactivity of this unique formylborane was also investigated. In this poster we will present the above mentioned discoveries.

[1] G. Erker, D. W. Stephan, Top. Curr. Chem. 2013, vol. 332 and vol. 334.

[2] a) A. J. P. Cardenas, B. J. Culotta, T. H. Warren, S. Grimme, A. Stute, R. Fro�hlich, G. Kehr, G.

Erker, Angew. Chem. Int. Ed. 2011, 50, 7567-7571; b) M. Sajid, A. Stute, A. J. P. Cardenas, B. J.

Culotta, J. A. M. Hepperle, T. H. Warren, B. Schirmer, S. Grimme, A. Studer, C. G. Daniliuc, R.

Fro�hlich, J. L. Petersen, G. Kehr, G. Erker, J. Am. Chem. Soc. 2012, 134, 10156-10168.

[3] M. Sajid, L.-M. Elmer, C. Rosorius, C. G. Daniliuc, S. Grimme, G. Kehr, G. Erker, Angew. Chem.

Int. Ed. 2013, 52, 2243-2246.

[4] M. Sajid, G. Kehr, C. G. Daniliuc, G. Erker, Angew. Chem. Int. Ed. 2014, 53, 1118-1121.

62

Poster 35

Acrylate Formation from CO2 and Ethylene Mediated by Nickel-Complexes – Mechanistic Studies

Philipp N. Plessow,a,b Andrey Y. Khalimon,b S. Chantal E. Stieber,b Núria Huguet,b Ivana Jevtovikj,b Ronald Lindner,b Michael Lejkowski,b Ansgar

Schäfer,a Michael Limbach,*b,c Peter Hofmann*b,d

aBASF SE, GVM/M, Ludwigshafen, Germany; bCaRLa, Heidelberg, Germany; cBASF SE,

GCS/C, Ludwigshafen, Germany; dRuprecht-Karls-Universität Heidelberg,Organisch-Chemisches Institut, Heidelberg, Germany

e-mail: [email protected]; [email protected]

The nickel-mediated synthesis of acrylates from carbon dioxide (CO2) and ethylene1,2,3 has been studied experimentally and theoretically. Included are theoretical investigations of the coupling of CO2 and ethylene as well as further reactivity models in the absence of auxiliaries mediated by nickel complexes bearing bidentate ligands. The sensitivity of the nickelalactone to bases1 and methyl iodide2,3 is also investigated. Although the formation of acrylic acid is thermodynamically and kinetically unfavorable, our computations demonstrate how these may be overcome by the addition of either a strong acid or Lewis acid/base combination. In support of the computational models, possible intermediates in the formation of sodium acrylate, methyl acrylate as well as silyl acrylates were isolated.

[1] M. L. Lejkowski, R. Lindner, K. Kageyama, G. É.; Bódizs, P. N. Plessow, I. B.

Müller, A. Schäfer, F. Rominger, P. Hofmann, C. Futter, S. A. Schunk, M. Limbach,

Chem. Eur. J. 2012, 18, 14017-14025. [2] C. Bruckmeier, M. Lehenmeier, W. Reichardt, S. Vagin, B. Rieger, Organometallics

2010, 29, 2199-2202. [3] P. N. Plessow, L. Weigel, R. Lindner, A. Schäfer, F. Rominger, M. Limbach, P.

Hofmann, Organometallics 2013, 32, 3327-3338.

63

Poster 36

Asymmetric Induction by Chiral Counterions in Enantioselective Hydrogenation using a Racemic Rh-BINAP Catalyst

Marcus Suberg, Rafael Krause, Giancarlo Franciò, Jürgen Klankermayer, Walter Leitner*

RWTH Aachen University, Institut für Technische und Makromolekulare Chemie (ITMC), Worringerweg

1, 52074 Aachen, Germany


The use of metal complexes bearing chiral ligands is one of the key technologies in enantioselective catalysis.1 In contrast, chiral solvents or additives have played a minor role and only recently have been used in combination with chiral, racemic or even with non-chiral catalysts as an external bias for exploring synergetic effects.2,3

In particular, we have shown that asymmetric induction can be achieved using a chiral anion in the Rh-catalysed hydrogenation with racemic BINAP ligand.4 The present work reports the synthesis of a new chiral Brønsted acid and the application of the corresponding anion in the Rh-catalysed asymmetric hydrogenation. Compared to our previous results, the amount of the chiral auxiliary was reduced, while increasing the enantioselectivity for this reaction.

OO

O

OO ∗ O

O

O

PPh2

Ph2P

RhS

NS

O

OO

O

63 % eeDCM, rt, 17 h, 40 bar H2

[1] R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New York, 1994.

[2] R. J. Philipps, G. L. Hamiton, F. D. Toste, Nat. Chem. 2012, 4, 603-6014.

[3] D. Chen, M. Schmitkamp, G. Franciò, J. Klankermayer, W. Leitner, Angew. Chem. 2008, 120, 7449-7451.

[4] D. Chen, B. Sundararaju, R. Krause, J. Klankermayer, P. H. Dixneuf, W. Leitner, ChemCatChem

2010, 2, 55-57.

64


Poster 37

Towards a Transition Metal-Catalysed Chapman-Type Rearrangement Joseph Tate, Guy Lloyd-Jones*

School of Chemistry, University of Edinburgh, United Kingdom e-mail: [email protected]

Despite the advancement of the Buchwald-Hartwig amination of phenol-derived pseudohalides,1 a general protocol for the conversion of phenols to aniline derivatives remains an enticing prospect. Conventional substrates of the Chapman rearrangement, which also affects CAr-O to CAr-N bond transformation, require heating at 200-300 °C for the intramolecular SNAr reaction to proceed (A).2 It is proposed that modified substrates could rearrange at lower temperatures via transition metal-catalysis (B). To date, trichloro- and trifluoroacetimidate analogues have resisted rearrangement.

OH O

NR2

R3R2N

O

R3 NHR2

R1 R1 R1 R1

[M] cat.

R1 = H, R2 = Ph, R3 = Ph

R2 = H, R3 = CCl3 or R2 = aryl/alkyl, R3 = CF3

A

B

[M] = Pd, Ni, Rh, Ru

300 °C

Alongside the aforementioned studies, evidence has also been gathered which casts doubt over the feasibility of the previously reported base-catalysed rearrangement of O-arylisoureas and an unexpected decomposition/activation pathway of a potential Pd(II) N-heterocyclic carbene precatalyst, (SIPr)Pd(Cp)(cinnamyl), has been identified.

[1] D. S. Surry, S. L. Buchwald, Chem. Sci. 2011, 2, 27.

[2] A. W. Chapman, J. Chem. Soc. Trans. 1925, 127, 1992.

65


Poster 38

A Short Asymmetric Synthesis of Vitamin E Andreas O. Termath, Hans-Günther Schmalz*

Department for Organic Chemistry, Greinstr. 4, University of Cologne e-mail: [email protected]

Due to its physiological importance and powerful antioxidant properties “vitamin E”, i.e. α-tocopherol (R,R,R-1), represents an essential food constituent of high commercial value.

MeO

OH OMe

HO

OMe

MeO

R'

O

O

MeO

R'

OCO2Me a. AlMe3, cat Cu/L*

b. LiCl, DMSO, H2O

83%

gram scale

2

2R:2S = 97 : 3

6 steps

O

OP N

Me

Ph

L*

2

35%

1

Noteworthy, all-rac-1 is industrially produced on a multi 10.000 tons/year scale and primarily used in animal nutrition1 even though the natural (R,R,R)-isomer (1) clearly exhibits the highest biological activity.2 As the growing demand of isomerically pure 1 for human applications cannot be satisfied from the limited natural sources, the development of stereoselective (and scalable) syntheses of (R,R,R)-α-tocopherol (1) represents an important challenge. We herein describe the efficient total synthesis of (R,R,R)-α-tocopherol (1) following a novel strategy, which exploits a highly stereoselective 1,4-addition to an activated chromenone.

[1] Bonrath et al., Angew. Chem. 2012, 124, 13134-13165. [2] S. K. Jensen, C. Lauridsen, in Vitamins & Hormones, G. Litwack, Ed. Academic Press: 2007; Vol.

76, 281-308.

66

Poster 39

Towards Understanding the Formation of Methyl Acrylate from Ethylene, CO2 and Methyl Iodide

Laura Weigel,a Philipp N. Pleßow,b Frank Rominger,a Michael Limbach,b Peter Hofmann*a,b

aOrganisch-Chemisches Institut, Universität Heidelberg, Germany bCaRLa (Catalysis Research Laboratory), Heidelberg, Germany


Since the 1980s nickelalactones have been discussed with regard to the formation of acrylic acid from CO2 and ethylene.1 However, nickelalactones are stable compounds and do not liberate acrylic acid. Methyl iodide induces the nickel-mediated stoichiometric reaction to methyl acrylate from CO2 and ethylene via nickelalactones.2 Kühn et al. described a mechanistic proposal for this reaction.3 We suggest a modified and extended mechanism for this reaction for the chelating ligand 1,2-bis(di-tert-butyl phosphino) ethane (dtbpe). 4 We were able to isolate reactive intermediates of the catalytic cycle such as the methylated nickelalactones which are accessible by methylation of the nickelalactones with methyl triflate or protonation of (dtbpe)Ni(η2-methyl acrylate) with HBArF, respectively.

[1] H. Hoberg, Y. Peres, C. Krüger, Y. H. Tsay, Y. H. Angew. Chem. Int. Ed. 1987, 26, 771. [2] C. Bruckmeier, M. W. Lehenmeier, R. Reichhardt, S. Vagin, B. Rieger, Organometallics 2010, 29,

2199.

[3] S. Y. T. Lee, M. Cokja, M. Drees, Y. Li, J. Mink, W. A. Herrmann, F. K. Kühn, ChemSusChem

2011, 4, 1275. [4] P. N. Pleßow, L. Weigel, R. Lindner, A. Schäfer, F. Rominger, M. Limbach, P. Hofmann,

Organometallics 2013, 32, 3327.

67

Poster 40

Alkylation of Amines with Alcohols: Catalysis by Cp*Ir(III)- Complexes and Mechanistic Investigations

Simone Wöckel,a,b Frank Rominger,c Peter Hofmann,a,c Michael Limbach*a,b

aCaRLa – Catalysis Research Laboratory, Im Neuenheimer Feld 584, D-69120 Heidelberg,

Germany; bBASF SE, Synthesis & Homogeneous Catalysis, Carl-Bosch-Strasse 38, D-67056

Ludwigshafen, Germany; cOrganisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg, Im

Neuenheimer Feld 270, D-69120 Heidelberg, Germany e-mail: [email protected]

Amines are of great industrial interest as starting materials or intermediates.1 We were interested in the metal-catalyzed alkylation of amines with alcohols via a hydrogen

borrowing mechanism since alcohols are readily available and the only byproduct in this transformation is water.2 We will present iridium-based complexes that are active catalysts in the alcohol amination reaction and tolerate a broad scope of substrates. 3 Additionally, we discuss catalyst initiation and

dissociation of the chelating ligand.4

[1] S. Bähn, S. Imm, L. Neubert, M. Zhang, H. Neumann, M. Beller, ChemCatChem 2011, 3, 1853-1864.

[2] D. Balcells, A. Nova, E. Clot, D. Gnanamgari, R. H. Crabtree, O. Eisenstein, Organometallics

2008, 27, 2529-2535. [3] A. Wetzel, S. Wöckel, M. Schelwies, M. K. Brinks, F. Rominger, P. Hofmann, M. Limbach, Org.

Lett. 2013, 15, 266-269. [4] S. Wöckel, P. N. Plessow, M. Schelwies, M. K. Brinks, F. Rominger, P. Hofmann, M. Limbach,

ACS Catal. 2014, 4, 152-161.

68

Poster 41

Efficient Hydrogen Liberation from Formic Acid Catalyzed by a Well-Defined Iron Pincer Complex under Mild Conditions

Thomas Zell, Burkhard Butschke, Yehoshoa Ben-David, David Milstein*Department of Organic Chemistry, Weizmann Institute of Science, 76100 Rehovot, Israel


Our group has recently applied iron pincer complexes as efficient catalysts for the hydrogenation of ketones1 and the hydrogenation of carbon dioxide to sodium formate in aqueous solutions of sodium hydroxide.2 Herein, we report on the formal reverse reaction, that is, the catalytic decomposition of formic acid to carbon dioxide and hydrogen. This reaction is an attractive approach to reversible hydrogen storage applications. The efficient and selective hydrogen liberation from formic acid is catalyzed by an iron pincer complex in the presence of trialkylamines (see scheme).3 Turnover frequencies up to 836 h−1 and turnover numbers up to 100 000 were achieved at 40 °C. A mechanism including well-defined intermediates is suggested on the basis of experimental and computational data.

[1] a) R. Langer, G. Leitus, Y. Ben-David, D. Milstein, Angew. Chem. Int. Ed. 2011, 50, 2120; b) R.

Langer, M. A. Iron, L. Konstantinovski, Y. Diskin-Posner, G. Leitus, Y. Ben-David, D. Milstein,

Chem. Eur. J. 2012, 18, 7196.

[2] R. Langer, Y. Diskin-Posner, G. Leitus, L. J. W. Shimon, Y. Ben-David, D. Milstein, Angew. Chem.

Int. Ed. 2011, 50, 9948.

[3] T. Zell, B. Butschke, Y. Ben-David, D. Milstein, Chem. Eur. J. 2013, 19, 8068.

69

Poster 42

Towards the Total Synthesis of the Epipolythiodiketopiperazine Scabrosin Acetate Hannes F. Zipfel, Erick M. Carreira*

Laboratorium für Organische Chemie, ETH Zürich, 8093 Zürich, Switzerland e-mail: [email protected]

The epipolythiodiketopiperazine (ETP) natural products are fungal metabolites that are all constructed around a sulfenylated diketopiperazine moiety. Several family members have a fused 6/5/6/5/6-ring system in common, but differ in their oxidation pattern of the A- and A’-rings. Scabrosin esters (1) are among the most densely functionalized members of the family, showing oxidation at all but two carbon atoms. In addition to their interesting structural features, they possess intriguing cytotoxic activity against a series of cancer cell lines.1 We are currently developing a concise and scalable synthesis of the core 6/5/6/5/6-ring system that allows the synthesis of Scabrosin acetate (1, R1,2 = Me) and its relatives (1, R1,2 ≠ Me).

N

N

O

O

O

O

O

SS

O

1R1 = R2 = Me: Scabrosin Acetate

R1

O R2

OA

A'

B'BC

[1] D. E. Williams, K. Bombuwala, E. Lobkovsky, E. D. de Silva, V. Karunaratne, T. M. Allen, J.

Clardy, R. J. Andersen, Tetrahedron Lett. 1998, 39, 9579-9582; M. A. Ernst-Russell, C. C. L. Chai,

A. M. Hurne, P. Waring, D. C. R. Hockless, J. A. Elix, Aust. J. Chem. 1999, 52, 279-283; C. C. L. Chai, J. A. Elix, P. B. Huleatt, P. Waring, Bioorg. Med. Chem. 2004, 12, 5991-5995.

70

Lecturer Catherine S. Cazin University of St Andrews School of Chemistry Purdie Building, North Haugh KY16 9ST, St Andrews, UK [email protected]

Jonathan Ellman Yale University Department of Chemistry CT 06520-8107, New Haven, USA [email protected]

Rolf Gleiter Heidelberg University Institute of Organic Chemistry Im Neuenheimer Feld 270 69120 Heidelberg, Germany [email protected]

A. Stephen K. Hashmi Heidelberg University Institute of Organic Chemistry Im Neuenheimer Feld 270 69120 Heidelberg, Germany [email protected]

Peter Hofmann Heidelberg University Institute of Organic Chemistry Im Neuenheimer Feld 270 CaRLa – Catalysis Research Laboratory Im Neuenheimer Feld 584 69120 Heidelberg, Germany [email protected]

Amir Hoveyda Boston College Department of Chemistry Merkert Chemistry Center, 2467 Massachusetts, Chestnut Hill, USA [email protected]

Xile Hu École Polytechnique Fédérale de Lausanne, Institute of Chemical Sciences and Engineering, Laboratory of Inorganic Synthesis and Catalysis EPFL-SB-ISIC, BCH 3305 1015 Lausanne, Switzerland [email protected]

William D. Jones University of Rochester Department of Chemistry NY 14627 Rochester, USA [email protected]

Masaharu Nakamura Kyoto University Internal Research Center for Elements Science (IRCELS), Institute for Chemical Research, Kyoto 611-0011 Uji, Japan [email protected]

Steve Nolan University of St Andrews School of Chemistry, Purdie Building, North Haugh KY16 9ST, St Andrews, UK [email protected]

Rocco Paciello BASF SE Homogeneous Catalysis, Building M313 Carl-Bosch-Strasse 38 67056 Ludwigshafen, Germany [email protected]

Peter Schuhmacher BASF SE, Process Research & Chemical Engineering, Building M311 Carl-Bosch-Strasse 38 67056 Ludwigshafen, Germany [email protected]

Walter Thiel Max-Planck-Institut für Kohlenforschung Kaiser-Wilhelm-Platz 1 45470 Mülheim an der Ruhr, Germany [email protected]

71










Participants Òscar Àrias Technische Universität Braunschweig Institut für Anorganische und Analytische Chemie Hagenring 30, 38106 Braunschweig, Germany [email protected]

Pedron Arrechea Massachusetts Institute of Technology Department of Chemistry [email protected]

Friedhelm Balkenhohl BASF SE Synthesis & Homogeneous Catalysis (GCS) – M313, Carl-Bosch-Strasse 38 67056 Ludwigshafen, Germany

Javier Borau-Garcia University of Calgary Department of Chemistry 2500 University Dr. NW Calgary, Alberta, T2N1N4 Canada [email protected]

Christopher Brown Heidelberg University Catalysis Research Laboratory (CaRLa) Im Neuenheimer Feld 584 D-69120 Heidelberg, Germany [email protected]

Jessica Llop Castelbou Universitat Rovira i Virgili Departament Química Física i Inorgànica, C/Marcel•lí Domingo s/n 43007 Tarragona, Spain [email protected]

Richard Collins University of Oxford Chemistry Research Laboratory Department of Chemistry, Mansfield Road, Oxford, OX1 3TA, UK [email protected]

Qinghai Deng Catalysis Research Laboratory (CaRLa) Im Neuenheimer Feld 584, 69120 Heidelberg, Germany [email protected]

Eric Derrah Heidelberg University Catalysis Research Laboratory (CaRLa) Im Neuenheimer Feld 584 69120 Heidelberg, Germany [email protected]

Andrea Di Giuseppe Universidad de Zaragoza Departamento Química Inorgánica, Instituto Síntesis Química y Catálisis Homogénea CSIC, C/ Pedro Cerbuna 12, 50009 Zaragoza, Spain [email protected]

Lutz H. Gade Heidelberg University Institute of Anorganic Chemistry Im Neuenheimer Feld 270 69120 Heidelberg, Germany and CaRLa - Catalysis Research Laboratory Im Neuenheimer Feld 584 69120 Heidelberg, Germany [email protected]

Morgan Gaydou Institute of Chemical Research of Catalonia (ICIQ) Av. Països Catalans 16 43007 Tarragona, Spain [email protected]

Konrad Gebauer Max-Planck Institut für Kohlenforschung Kaiser Wilhelm-Platz 1 45470 Mülheim a. d. R, Germany [email protected]

Rebecca Green University of California Department of Chemistry Berkeley, California, 94720, USA [email protected]

72












Diana Haas Ludwig-Maximilians-Universität München, Department Chemie Butenandtstr. 5-13, Haus F 81377 München, Germany [email protected]

Max Martin Hansmann Heidelberg University Institute of Organic Chemistry Im Neuenheimer Feld 270 69120 Heidelberg,Germany [email protected]

Shuji Higuchi Kyoto University, Division Knowledge & Technology Transfer and Innovation, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan

Jennifer Howell University of Illinois Department of Chemistry 600 South Mathews Ave. Urbana, IL 61801, USA [email protected]

Núria Huguet CaRLa – Catalysis Research Laboratory Im Neuenheimer Feld 584 D-69120 Heidelberg, Germany [email protected]

Atsuhiro Iimuro Department of Chemistry, Graduated School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan [email protected]

Ivana Jevtovikj CaRLa – Catalysis Research Laboratory, Im Neuenheimer Feld 584, D-69120 Heidelberg, Germany [email protected]

Phillip Jolly CaRLa - Catalysis Research Laboratory Im Neuenheimer Feld 584, D-69120 Heidelberg, Germany [email protected]

Dipannita Kalyani St. Olaf College [email protected]

Andrey Khalimon CaRLa – Catalysis Research Laboratory, Im Neuenheimer Feld 584, D-69120 Heidelberg, Germany [email protected]

Philipp Koschker Albert-Ludwigs-Universität Freiburg Institut für Organische Chemie und Biochemie, Albertstrasse 21 79104 Freiburg im Breisgau, Germany [email protected]

Lisa Kötzner Max-Planck-Institut für Kohlenforschung Kaiser Wilhelm-Platz 1 45470 Mülheim an der Ruhr [email protected]

Valeri Leich Aachen University Institute of Inorganic Chemistry RWTH Landoltweg 1 52074 Aachen, Germany [email protected]

Michael Limbach BASF SE Synthesis & Homogeneous Catalysis (GCS/C) – M313 67056 Ludwigshafen, Germany and CaRLa - Catalysis Research Laboratory Im Neuenheimer Feld 584 69120 Heidelberg, Germany [email protected]

73













Tom Lyons University of North Carolina at Chapel Hill, Chapel Hill NC 27599, USA [email protected]

Jaroslaw Mormul CaRLa - Catalysis Research Laboratory Im Neuenheimer Feld 584, D-69120, Heidelberg, Germany [email protected]

Melanie Kim Müller TU Kaiserslautern Erwin-Schrödinger-Str. 54 67663 Kaiserslautern, Germany [email protected]

Michael Mulzer CaRLa - Catalysis Research Laboratory Im Neuenheimer Feld 584 D-69120 Heidelberg, Germany [email protected]

Naohisa Nakagawa Kyoto University International Research Center for Elements Science (IRCELS), Institute for Chemical Research (ICR) Uji, Kyoto, 611-0011, Japan [email protected]

Ryo Nakano The University of Tokyo Department of Chemistry and Biotechnology, Graduate School of Engineering, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan [email protected]

Pascal Nösel Heidelberg University Institute of Organic Chemistry Im Neuenheimer Feld 271 69120 Heidelberg, Germany [email protected]

Sander Oldenhof University of Amsterdam van ’t Hoff Institute for Molecular Sciences, The Netherlands [email protected]

Philipp Plessow CaRLa - Catalysis Research Laboratory Im Neuenheimer Feld 584 69120 Heidelberg, Germany [email protected]

Lars Krogager Ransborg Aarhus University Center for Catalysis, Department of Chemistry, Denmark [email protected]

Torsten Roth Heidelberg University Institute of Organic Chemistry, INF 270, 69120 Heidelberg, Germany [email protected]

Andreas Rühling Westfälische-Wilhelms Universität Organisch-Chemisches Institut Corrensstr. 40, 48149 Münster, Germany [email protected]

Muhammad Sajid Westfälische-Wilhelms Universität Organisch-Chemisches Institut Corrensstr. 40, 48149 Münster, Germany [email protected]

Chantall Stieber CaRLa - Catalysis Research Laboratory Im Neuenheimer Feld 584 69120 Heidelberg, Germany [email protected]

74






mailto:%[email protected]

mailto:%[email protected]



Markus Suberg RWTH Aachen University Institut für Technische und Makromolekulare Chemie (ITMC) Worringerweg 1 52074 Aachen, Germany [email protected]

Joseph Tate University of Edinburgh School of Chemistry, UK [email protected]

Andreas Termath University of Cologne Department for Organic Chemistry, Greinstr. 4, Germany [email protected]

Thomas Weber BASF Se, Science Relations & Innovation Management, Building B001, Carl-Bosch-Strasse 38, 67056 Ludwigshafen, Germany

Laura Weigl Heidelberg University Institute of Organic Chemistry Im Neuenheimer Felder 271 69120 Heidelberg, Germany [email protected]

Simone Wöckel Catalysis Research Laboratory (CaRLa) Im Neuenheimer Feld 584 69120 Heidelberg, Germany [email protected]

Thomas Zell Weizmann Institute of Science Department of Organic Chemistry 76100 Rehovot, Israel [email protected]

Hannes Zipfel ETH Zürich Laboratorium für Organische Chemie 8093 Zürich, Switzerland [email protected]

75






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