Research Interest of the Gansäuer Group

Here you can find an overview about our research interests!

As highlighted in the resolution adopted by the general assembly of the United Nations ‘Transforming our world: the 2030 Agenda for Sustainable Development’, sustainability is a global key-issue.1 Catalysis is an enabling branch of science providing access to novel materials and processes. It is therefore ideally suited to deliver sustainable solutions for the demands of modern societies. As pointed out by Anastas2 this is so, because catalysis can be employed


  • in the design of processes that maximize the amount of raw material ending up in the product
  • in the use of renewable material feed-stocks and energy sources
  • in the use of safe, environmentally benign substances, including solvents
  • in avoiding the production of waste.

Moreover, catalysis offers unique perspectives for the synthesis of substances that increase the quality of live, such as drugs, polymers, and materials for energy conversion.


To demonstrate the potential of catalysis in uncharted fields, we are focusing on two broad research areas:


·         We are use as radicals as key-intermediates for catalysis in single electron steps, a concept that has emerged from our investigations on sustainable catalytic radical reactions where the metal shuttles between neighboring oxidation states. It features high atom-economy, catalyst-controlled of pertinent selectivities, and allows the exploitation of renewable energy sources in discovering novel reactivity profiles.

·         We often employ epoxides as ‘spring-loaded’ substrates for the design of novel catalytic reactions. The release of ring-strain provides high thermodynamic driving forces for our reactions. Moreover, epoxides are easy to prepare in enantiomerically pure form and, therefore, provide a convenient entry into a large manifold of stereoselective reactions for the synthesis of enantiomerically pure products.

·         Conceptually, enantio- and stereoselective catalysis involving sp3-hybridized C-atoms is different from catalysis as sp2-centers. Therefore, the development of novel approaches to stereoselectivity is a key research area of the group.

·         An essential aspect of catalysis is the choice of catalyst, of course. We are particularly involved in the use of complexes of earth abundant early 3d-metals (mainly Ti, but also Cr). They not only show a unique electron transfer reactivity. With respect to sustainability, they are highly attractive because they are readily available and essentially non-toxic.

1. Catalysis in single electron steps:

Catalysis in single electron steps is a concept that allows conducting radical reactions under reagent (or catalyst) control and with high or complete atom-economy.3 Catalysis in single electron steps is related to classical organometallic catalytic reactions, such as the Heck-reaction or Pd-catalyzed cross-coupling, because it is initiated by an oxidative addition and terminated by a reductive elimination. However, the steps occur in single electron steps4 and it is therefore mandatory to identify metal complexes than can easily shuttle between neighboring oxidation states (and not in two electron steps). The radical translocation step that takes place between oxidative addition and reductive elimination can in principle be any elementary radical reaction, including C-C bond forming steps and C-H bond forming steps.

In our research, epoxides are predominantly used as radical precursors and the titanocene(IIII)/titanocene(IV) redox couple mediates catalysis. Examples of reactions proceeding by catalysis in singe electron steps are epoxide arylations,5 epoxide hydrosilylations,6 epoxide hydrogenation and hydroboration by cooperative catalysis,7 acetal forming reactions, and the use of renewable energy sources for catalyst generation.9,10

a)     Epoxide arylations

© Andreas Gansäuer

The catalytic cycle of the epoxide arylation is comprised of four steps. Radical generation is accomplished by single electron oxidative addition of the titanocene(III) catalyst to the epoxide. After radical translocation via addition to the arene, the single electron reductive elimination takes place by the ‘back electron transfer’ from the radical σ–complex to the pendant titanocene(IV) and subsequent protonation of the Ti-O bond. The last two steps may be concerted and constitute a proton coupled electron transfer (PCET).

The substrates are readily available, the reaction can be carried out with low catalyst loading, catalyst performance can be fine-tuned by modulation of the redox-properties of the catalyst, and the reaction is an excellent and sustainable method for the preparation of N-heterocycles.

b)     Epoxide hydrosilylation

© Andreas Gansäuer

Epoxide hydrosilylations have been a class of virtually unexplored reactions. Our titanocene catalyzed reaction proceeds via catalysis in single electron steps and features an intramolecular HAT as key step. The reactions are amongst the most diastereoselective reductions of acyclic radicals. Our hydrosilylation is of high interest for large scale synthesis because it can be carried out with low catalyst loading (<1 mol%) and the less substituted alcohols can be obtained with very high regioselectivity. Catalyst regeneration is accomplished by a σ–bond metathesis reaction.

Recently, we have shown how our reaction can be applied to the synthesis of the synthesis of stereochemically uniform deuterated alcohols that should be of interest for deuterated drugs. To achieve high deuterium incorporation (DI > 98%), we have devised a novel protocol for catalyst activation.11

c)     Cooperative catalysis

© Andreas Gansäuer

The hydrogenation of epoxides to the less-substituted epoxide is a largely unexplored area of research. However, it is very attractive for a two-step synthesis of anti-Markovnikov alcohols consisting of olefin epoxidation and epoxide hydrogenation. Together with the group of Norton (Columbia University, USA), we have developed a system featuring Ti- and Cr-catalysts for a unique H2-activation and epoxide hydrogenation.8 Our work was highlighted in the ‘Frankfurter Allgemeine Zeitung (FAZ)’. 

Milder and more general conditions for epoxide reduction, cyclization reactions with epoxides and regiodivergent epoxide opening have invented by using Li[BH4] as the terminal reductant in Ti/Cr cooperative catalysis. The reaction proceeds via a different mechanism featuring a H-atom transfer from Ti to Cr.12

2. Use of renewable energy sources for catalyst activation:9,10

© Andreas Gansäuer

A key-step of all of our reactions featuring catalysis in single electron steps is the initial reduction of the titanocene(IV) precatalyst to a catalytically active titanocene(III) complex. We have recently shown how this step can be realized using electrolysis in the presence of hydrogen bonding additives or with visible light. 

With the electrochemical reduction, the ensuing reactions can lead to more active catalysts and result in substantially more sustainable reaction conditions.

The photochemically excited titanocene(IV) complexes are strong oxidants that can be easily reduced to the catalytically active titanocene(III) compounds.13 The oxidized quenchers are attractive reagents themselves and can be used in many novel transformations. Together with the group of Vöhringer (Physical Chemistry, University of Bonn), the entry events of photoredox catalysis with titanocene(IV) complexes have been elucidated.14

© Andreas Gansäuer

3. Stereoselective catalysis with epoxides

Opening reactions of suitably substituted epoxides can lead to important classes of compounds provided that the regioselectivity of ring opening can be controlled efficiently. We have recently focused on the synthesis of 1,3– and 1,4–difunctionalized building blocks from α– or β–functionalized epoxides.

a)     Regiodivergent epoxide opening (REO)

Enantiomerically pure cis-1,2-disubstituted epoxides can be opened with high regioselectivity through ET from enantiomerically pure titanocene(III) complexes. Reductive radical trapping and catalyst regeneration results in the liberation of the desired products typically in high yield and selectivity. Since our process is catalyst controlled the enantiomer of the catalyst provides the regioisomer of the product in high yield and almost equally high regioselectivity. Therefore, two products can be prepared with high selectivity and yield from a single substrate by judicious choice of the catalyst. Our regiodivergent process was amongst the first efficient examples in the field of epoxide opening and provides access to numerous (poly-) functional building blocks for the synthesis of complex products.15 With cooperative Ti-/Cr-catalysis, more sustainable conditions for the REO have recently become available.

© Andreas Gansäuer

We have shown how regiodivergent catalysis can employed in a highly sustainable synthesis of either enantiomerically pure indolines or tetrahydroquinolines from the same substrates by radical arylation.16

© Andreas Gansäuer

b)     Converging diverging reactions

One of the virtues of radical chemistry is the loss of absolute configuration after radical generation from an sp3-hybridized C-atom. This feature can be exploited in reactions converging mixtures of isomers into one product provided that the radical formed is trapped with high selectivity. We have realized such a process by transforming mixtures of epoxides to enantiomerically and diastereomerically ‘pure’ alcohols. The reaction provides a rapid access to enantiomerically pure alcohols that are otherwise obtained by a hydroboration/oxidation sequence.17

© Andreas Gansäuer


Reactions of Aziridines

Functional Organometallic Compounds

Recently, we have demonstrated that substituted aziridines are also excellent substrates for radical generation. However, for titanocene catalysis, it is mandatory to use N-acylated aziridines as substrates to enforce binding to the catalyst. 

We have devised a novel modular synthesis of structurally and functionally diverse cationic titanocenes.19 The compounds are highly interesting as catalysts in novel reactions, such as epoxide reductions.

Over the years we have cooperated with many national and international groups on many aspects of our work, such as catalyst design, reaction design, synthesis of complex molecules, and mechanistic as well as electrochemical problems. Many of these projects involve joint grants and active exchange of students between the groups. Our international partners include the groups of Bob Flowers at Lehigh University (USA), Kim Daasbjerg (Aarhus, DK), Jack R. Norton (Columbia University, USA), an Streuff (University of Uppsala, S) Juan Manuel Cuerva and Enrique Oltra (Granada, E). Within the framework of the SFBs in Bonn we have actively interacted with the groups of Stefan Grimme, Olav Schiemann, and Peter Vöhringer



2) Anastas, P. T.; Kirchhoff, M. M.; Acc. Chem. Res. 2002, 35, 686-694.

3) Gansäuer, A. Hildebrandt, S.; Vogelsang, E; Flowers, R. A. II Dalton Trans. 2016, 45, 448-452. DOI: 10.1039/C5DT03891J

4) Gansäuer A.; Fleckhaus, A.; Alejandre Lafont, M.; Okkel, A.; Kotsis, K; Anoop, A.; Neese, F. J. Am. Chem. Soc. 2009, 131, 16989-16999. DOI: 10.1021/ja907817y

5) a) Gansäuer, A.; , Hildebrandt, S.; Michelmann, A.; Dahmen, T.; von Laufenberg, D.; Kube, C.; Fianu, G. D.; Flowers, R. A. II Angew. Chem. Int. Ed. 2015,54, 7003-7006. DOI: 10.1002/anie.201501955; b) Richrath, R. B.; Olyschläger, T.; Hildebrandt, S.; Enny, D. G.; Fianu, G. D.; Flowers, R. A. II; Gansäuer, A. Chem. Eur. J. 2018, 24, 6371-6379. DOI: 10.1002/chem.201705707

6) Schwarz G. Henriques, D.; Zimmer, K.; Klare, S.; Meyer, A.; Rojo-Wiechel, E.; Bauer, M.; Sure, R.; Grimme, S.; Schiemann, O.; Flowers, R. A. II; Gansäuer, A. Angew. Chem. Int. Ed. 2016, 55, 7671-7675. DOI: 10.1002/anie.201601242

7) Yao, C.; Dahmen, T.; Gansäuer, A.; Norton, J. Science 2019, 364, 764-767. DOI: 10.1126/science.aaw3913

8) Funk, P.; Richrath, R. B.; Bohle, F.; Grimme, S.; Gansäuer, A.; Angew Chem. Int. Ed. 2021, 60, 5482-5488. DOI: 10.1002/anie.202013561

9) a) Liedtke, T.; Spannring, P.; Riccardi, L.; Gansäuer, A. Angew. Chem. Int. Ed. 2018, 57, 5006-5010. DOI: 10.1002/anie.201800731   b) Hilche, T.; Reinsberg, P. H.; Klare, S.; Liedtke, T.; Schäfer, L.; Gansäuer, A.; Chem. Eur. J. 2021, 27, 4903-4912. DOI: 10.1002/chem.202004519

10) Zhang, Z.; Richrath, R. B.; Gansäuer, A.; ACS Catal. 2019, 9, 3208-3212. DOI: 10.1021/acscatal.9b00787

11) Schwarz G. Henriques, D.; Rojo-Wiechel, E.; Klare, S.; Mika, R.; Höthker, S.; Schacht, J. H.; Schmickler, N.; Gansäuer, A.; Angew Chem. Int. Ed. 2022, 61, e202114198. DOI: 10.1002/anie.202114198

12) Heinz, M.; Weiss, G.; Shizgal, G.; Panfilova, A.; Gansäuer, A.; Angew. Chem. Int. Ed. 2023, 62, e202308680. DOI: 10.1002/anie.202308680

13) Zhang, Z.; Hilche, T.; Slak, D.; Rietdijk, N.; Oloyede, U. N.; Flowers, R. A. II; Gansäuer, A.; Angew. Chem. Int. Ed. 2020, 59, 9355-9359. DOI: 10.1002/anie.202001508

14) Schmidt, J.; Domenianni, L. I.; Leuschner, M.; Gansäuer, A.; Vöhringer, P.; Angew. Chem. Int. Ed. 2023, 62, e202307178. DOI: 10.1002/anie.202307178

15) a), Funken, N.; Zhang, Y.-Q.; Gansäuer, A. Chem. Eur. J. 2017, 23, 19-32. DOI: 10.1002/chem.201603993; b) Funken, N.; Mühlhaus, F.; Gansäuer, A. Angew. Chem. Int. Ed. 2016, 55, 12030-12034. DOI: 10.1002/anie.201606064  

16) Mühlhaus, F.; Weißbarth, H.; Dahmen, T.; Schnakenburg, G.; Gansäuer. A. Angew. Chem. Int. Ed. 2019, 58, 14208-14212. DOI: 10.1002/anie.201908860

17) Höthker, S.; Mika, R.; Goli, H.; Gansäuer, A.; Chem. Eur. J. 2023, 49, e202301031. DOI: 10.1002/chem.202301031

18) Zhang, Y.-Q.; Vogelsang, E.; Qu, Z.-W.; Grimme, S.; Gansäuer, A. Angew. Chem. Int. Ed. 2017, 56, 12654-12657. DOI: 10.1002/anie.201707673  

19) Gansäuer, A.; Franke, D.; Lauterbach, T.; Nieger, M. J. Am. Chem. Soc. 2005, 127, 11622-11623. DOI: 10.1021/ja054185r

20) Zhang, Y.-Q.; Jakoby, V.; Stainer, K.; Schmer, A.; Klare, S.; Bauer, M.; Grimme, S.; Cuerva J. M.; Gansäuer, A. Angew Chem. Int. Ed. 2016, 55, 1523-1526. 10.1002/anie.201509548

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