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Mario Waser

Assoc. Univ.-Prof. Dr. Mario Waser

Assoc. Univ.-Prof. Dr. Mario Waser (Back to Team Overview)
Associate Professor

Office: T 306, Lab: T 326
Phone: +43 732 2468 8748
Fax: +43 732 2468 8747
mario.waser(/\t)jku.at

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ORCID

0000-0002-8421-8642



Research Interests

Organocatalytic Methods for the Synthesis of (Fluorinated) Biologically Active Compounds
Our group is interested in the use of chiral organocatalysts to access compounds or structural motives that are of interest to biological or medicinal chemists, either because of their biological properties themselves, or because of their versatility to serve as key-intermediates in the synthesis of biologically active target molecules. Hereby we have a target-driven approach as well as interest in the development of new methods to access such molecules in a more efficient way. Special focus hereby is on the development of asymmetric fluorination methods towards chiral fluorinated amino acids and peptides.
FWF Project: „Syntheses of Chiral Fluorinated Amino Acids and Peptides“ (P30237)

Bifunctional Chiral Ammonium Salt Catalysis
Chiral quaternary ammonium salt catalysis is one of the outstanding catalytic principles nowadays. Over the last years the importance of an additional catalytically active unit in these catalysts became obvious and thus we are highly interest in the development of novel bifunctional chiral quaternary ammonium salt catalysts and application thereof for novel transformations.

Ammonium Enolate Mediate Reactions
In addition to these catalysis-based projects we are also interested in exploring the applicability of (a)chiral ammonium enolates for the (dia)stereoselective formation small ring carbo- and heterocycles. These structural motifs are highly important as they are often the functional groups of choice in key-intermediates in complex natural product syntheses. Accordingly the development of alternative synthesis strategies for such compounds are of high interest nowadays.
FWF Project: „Syntheses of (Chiral) Hetero- and Carbocycles Using Ammonium Enolates“ (P26387)




Generous financial support by the Austrian Science Funds FWF is gratefully acknowledged.

 

Running Projects

Syntheses of Chiral Fluorinated Amino Acids and Peptides
(FWF stand alone project P30237, starting 01/2018)


Abstract: The replacement of hydrogen atoms by fluorine in organic molecules has become a very important and powerful tool in various fields of research, mainly because of the fact that such a modification usually has a very dramatic effect on the physical, chemical, biological, and medical properties of these compounds. One class of fluorine containing compounds that has attracted a lot of interest for biomedical applications are fluorine containing amino acids and peptides. However, it is fair to say that the synthesis of chiral fluorinated amino acids or peptides still represents a major synthetic challenge. In this project plan to overcome this current limitation by establishing novel catalytic synthesis strategies to access chiral fluorinated a- and b-amino acid derivatives or peptides. Once successful, this project should thus deliver new powerful synthesis tools that will be of interest to organic and medicinal chemists and will finally give access to compounds that were not accessible with the existing state of the art methods.




Syntheses of (Chiral) Hetero- and Carbocycles Using Ammonium Enolates
(FWF stand alone project P26387, since 09/2014)


Abstract: The development of powerful, generally applicable, and highly efficient synthetic transformations is one of the ultimate goals in (organic) chemistry, especially considering the increasing demand for complex molecules with a variety of different functions in our society nowadays (pharmaceutical applications, agrochemicals, material science,..). Amongst the frequently found structural motives, highly functionalized small and medium ring size chiral (hetero)-cycles are of uttermost importance, as they present the key-scaffold in a large variety of biologically active (natural) products. In addition they serve as versatile intermediates in the synthesis of biologically active molecules. Accordingly, novel powerful strategies to access them in an efficient, economic, and direct fashion are an important task, not only for organic chemists working academia, but also for medicinal chemists searching for new lead compounds or for industrial (pharmaceutical) applications.
The use of (chiral) ammonium enolates (either preformed or generated in situ by using a catalyst) to carry out demanding stereoselective reactions is a powerful and unique strategy, giving access to transformations that are not possible using any other (catalytic) methods. However, having a closer look at the use of this unique strategy to facilitate (stereoselective) organic reactions it is fair to say that, although impressive (stereoselective) examples have been reported recently, it seems reasonable that this methodology holds much more promise for further investigations and the development of significantly more complex and outstanding applications. Thus, it is the main target of this project to address transformations that will give access to a variety of highly important cyclic structural motives that represent major synthesis challenges, as other commonly employed methods are still not powerful enough.
Accordingly, this project will introduce versatile strategies to facilitate the activation and use of easily available starting materials in a unique and unprecedented fashion and thus will provide new powerful methodologies to the standard toolbox employed by chemists to obtain important highly functionalized cyclic compounds straightforwardly.

Project Publications:
Please see publications 31, 33, 39, 40, 44, 47, 48, 49 from our general publication overview for further details about the research carried out in the course of this project.




Finished Projects

Chiral Ammonium Salts Meet Transition Metal Catalysis
(FWF Lise Meitner funding M1602, 02/2014 - 02/2015)


Principle Investigator:
Dr Raghunath Chowdhury

Abstract: The efficient and stereoselective construction of complex molecular architectures is one of the ultimate goals in chemistry and the use of small molecule organic catalysts (organocatalysts) has proven to be highly useful to achieve complex transformations starting from simple easily available starting materials in a large variety of different case studies. Hereby, non-covalent catalysis modes are amongst the most versatile approaches to mimic Nature, usually benefitting from mild and easy to handle reaction conditions, environmentally benign reagents, and high efficiencies. The use of chiral cations (especially chiral ammonium salt phase-transfer catalysts (PTCs)) as catalysts has obtained a prominent and outstanding position and has contributed significantly to the field of asymmetric catalysis. The enormous potential of these catalysts lies in the fact that (theoretically) every reaction involving anionic or even just highly Lewis basic intermediates (starting materials) can be affected and controlled by these cationic catalysts.
Considering the high potential of chiral PTCs to facilitate reactions where other methods clearly fail, we are confident that the use of chiral PTCs holds much promise to facilitate a series of highly demanding complex transformations, thus addressing some longstanding synthesis challenges. Although the synergistic combination of complementary activation modes has emerged as a powerful tool for complex transformations, it comes as a surprise that so far only a few reports about the synergistic combination of chiral PTCs with complementary activation modes have been published.
It is the main target of this project to carry out a systematic feasibility study of the combined use of chiral phase-transfer catalysts with complementary transition metal catalysts in a synergistic (or cascade) fashion. The high value of such an approach will be the benefit of employing the unique nucleophile-activation potential of chiral cation-based catalysts in combination with the well-described electrophile activating properties of transition metal catalysts. Accordingly, the successful implementation of the herein investigated reactions will broaden the field of asymmetric catalysis in general, as substrates which have so far not been useable in such approaches in a catalytic stereoselective manner can be directly employed to obtain valuable chiral compounds in just a single step. Thus this project should provide the community with outstanding new tools to solve longstanding problems and to get access to chiral building blocks that are otherwise only difficultly accessible in a stereoselective fashion under mild and environmentally friendly conditions by using easily tuneable and easy to handle catalysts.

Project Publications:
Please see publications 32 and 50 from our general publication overview for further details about the research carried out in the course of this project.




Novel Tartaric Acid Derived Asymmetric Organocatalysts
(FWF stand alone project P22508, 09/2010-09/2014)


Coworkers:
Drin Katharina Gratzer
Dr Richard Herchl
Dr Guddeangadi N. Gururaja

Abstract: The ability to control the three-dimensional structure of the molecular architecture is one of the primary targets in synthetic organic chemistry. Amongst the various ways of creating enantiomerically enriched products, catalytic methods are considered to be the most appealing as the use of stoichiometric amounts of valuable chiral reagents can be avoided, thus making optimum use of the chiral pool. Besides enzymatic and metal catalyzed asymmetric transformations, the use of sub-stoichiometric amounts of organic molecules (so called organocatalysts) has proven to possess an enormous potential for the catalysis of stereoselective reactions. Among the easily available natural chiral sources, tartaric acid has obtained a prominent position not only for historical reasons, but especially due to the fact that both enantiomers are readily available from natural sources. Surprisingly, although tartaric acid derivatives are almost omnipresent in metal catalysis, their use as chiral organocatalysts has so far been limited to a few applications only. Due to the fact that tartaric acid represents a very unique carbon skeleton possessing electronic and steric properties different from other commonly used chiral moieties the primary target of this project is the synthesis of novel tartaric acid derived organocatalysts and their application in asymmetric catalysis. As both, L- and D-tartaric acid are easily and cheaply available, access to both enantiomers of new catalysts is guaranteed.
Among the different activation modes, which are hitherto known in organocatalysis, the main focus herein lies on the synthesis of chiral ammonium salts, chiral Lewis acids/bases, and bifunctional catalysts. These compounds should enable the catalysis of a wide variety of different fundamental reactions. Therefore, in each case the ability of the new catalysts for the asymmetric catalysis of reactions like alkylations, allylations, aldol type reactions, or cyclizations will be investigated. Furthermore, a careful investigation concerning the crucial structural parameters of the novel catalysts will be undertaken.
The development of these novel organocatalysts will broaden the scope of organocatalysis as it will make use of one of the most easily available and cheapest natural chiral sources which has so far not been exploited much in this field. Furthermore, due to the characteristic and unique structural features of these catalysts, different reactivities compared to the currently used organocatalysts seem to be possible.

Project Publications:
Please see publications 13, 15, 18, 21, 22, 23, 25, 26, 27, 29 from our general publication overview for further details about the research carried out in the course of this project.