Project

Back to overview

New Catalytic C-C Bond Forming Reactions: Asymmetric Alkynylation of Enolates

English title New Catalytic C-C Bond Forming Reactions: Asymmetric Alkynylation of Enolates
Applicant Waser Jérôme
Number 134550
Funding scheme Project funding (Div. I-III)
Research institution Institut des sciences et ingénierie chimiques EPFL - SB - ISIC
Institution of higher education EPF Lausanne - EPFL
Main discipline Organic Chemistry
Start/End 01.06.2011 - 31.05.2015
Approved amount 265'874.00
Show all

Keywords (5)

Synthesis; Catalysis; Hypervalent Iodine; Alkynes; Azides

Lay Summary (English)

Lead
Organic synthesis occupies a privileged position in our life and contributes to our health and comfort. To follow up with our needs, the pharmaceutical industry, as well as the life and materials science, are in constant need for new chemical structures. The goal of this project is to take over this task and to develop new synthetic tools for applications, in particular stereoselective reactions for C-C and C-N bond formation will be developed to construct the backbone of organic molecules.
Lay summary
Organic synthesis occupies a privileged position in our modern life and contributes to our everyday comfort. To follow up with the growing needs of humanity, the pharmaceutical industry, as well as the life and material sciences, are in constant need for new chemical structures to develop bioactive substances for medicine or useful materials.
The carbon backbone constitutes the central core of many organic molecules, and its selective elaboration and functionalization are one of the main tasks of organic synthesis. Despite decades of research, synthesis remains a long and expensive process, as soon as complex molecules are targeted. In a context of growing concern about the limited environmental resources and the hazards associated with chemical waste, new reactions are highly desired to increase the flexibility and efficiency of organic synthesis. Due to the constantly increasing economical pressure, pharmaceutical and chemical industries usually cannot afford to spend time and money on fundamental reaction development and have to rely on established procedures. In so doing, they limit themselves, both in the structure of the compounds they can make and in the efficiency of the syntheses.
The goal of this project is to take over this important task and to develop new synthetic tools for applications in academy and industry. To achieve this goal, new stereoselective reactions will be developed to construct the carbon backbone of organic molecules. Catalytic processes will allow limiting the amount of generated waste as well as the cost of the reagents.
This project at the Laboratory of Catalysis and Organic Synthesis (LCSO, http://lcso.epfl.ch/) at the EFPL will contribute to the development of new chemical processes for C-C  and C-N bond formations to access bioactive molecules, an essential task towards a cleaner, more sustainable chemistry and for the successful treatment of diseases. The specific focus of the research will be in the catalytic asymmetric alkynylation and azidation of enolates. The acetylenes and azides introduced using these new methods are among the most useful functional groups in organic chemistry. Furthermore, they have found broad applications in the fields of organic materials and chemical biology. Consequently, the development of new methods to access these extremely versatile building blocks will have a strong impact, not only in fundamental organic chemisty, but also in neighbouring more applied fields.
Direct link to Lay Summary Last update: 15.07.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Cyclic Hypervalent Iodine Reagents for Atom-Transfer Reactions: Beyond Trifluoromethylation
Li Yifan, Hari Durga Prasad, Vita Maria Victoria, Waser Jerome (2016), Cyclic Hypervalent Iodine Reagents for Atom-Transfer Reactions: Beyond Trifluoromethylation, in ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 55(14), 4436-4454.
Cyclic Hypervalent Iodine Reagents and Iron Catalysts: The Winning Team for Late-Stage C-H Azidation
Vita Maria Victoria, Waser Jerome (2015), Cyclic Hypervalent Iodine Reagents and Iron Catalysts: The Winning Team for Late-Stage C-H Azidation, in ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 54(18), 5290-5292.
Enantioselective Synthesis of Homoallylic Azides and Nitriles via Palladium-Catalyzed Decarboxylative Allylation
Vita Maria Victoria, Caramenti Paola, Waser Jerome (2015), Enantioselective Synthesis of Homoallylic Azides and Nitriles via Palladium-Catalyzed Decarboxylative Allylation, in ORGANIC LETTERS, 17(23), 5832-5835.
Enantioselective Synthesis of Polycyclic Carbocycles via an Alkynylation–Allylation–Cyclization Strategy
Vita Maria Victoria, Miéville Pascal, Waser Jerome (2014), Enantioselective Synthesis of Polycyclic Carbocycles via an Alkynylation–Allylation–Cyclization Strategy, in Organic Letters, 16(21), 5768.
Azidation of Beta-Keto Esters and Silyl Enol Ethers with a Benziodoxole Reagent
Vita Maria Victoria, Waser Jérôme (2013), Azidation of Beta-Keto Esters and Silyl Enol Ethers with a Benziodoxole Reagent, in Organic Letters, 15, 3246-3249.
Ethynylbenziodoxolones (EBX) as Reagents for the Ethynylation of Stabilized Enolates
Fernandez Gonzalez Davinia, Brand Jonathan P., Mondière Régis, Waser Jérôme (2013), Ethynylbenziodoxolones (EBX) as Reagents for the Ethynylation of Stabilized Enolates, in Advanced Synthesis & Catalysis, 355, 1631-1639.
Asymmetric Organocatalysis Meets Hypervalent Iodine Chemistry for the alpha-Functionalization of Carbonyl Compounds
Gonzalez Davinia Fernandez, Benfatti Fides, Waser Jerome (2012), Asymmetric Organocatalysis Meets Hypervalent Iodine Chemistry for the alpha-Functionalization of Carbonyl Compounds, in CHEMCATCHEM, 4(7), 955-958.
Cyclopropane and Hypervalent Iodine Reagents: High Energy Compounds for Applications in Synthesis and Catalysis
Fernández González Davinia, De Simone Filippo, Brand Jonathan, Nicolai Stefano, Waser Jerome (2011), Cyclopropane and Hypervalent Iodine Reagents: High Energy Compounds for Applications in Synthesis and Catalysis, in Chimia, 65, 649-651.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
OMCOS Poster Pd(0)-Catalyzed Enantioselective Synthesis of α-Alkynyl, α-Azido and α-Cyano Ketones 28.06.2015 Sitges, Spain Vita Maria Victoria;
Swiss chemical Society Fall meeting Poster Pd(0)-Catalyzed Enantioselective Synthesis of 1,5-Enynes 12.09.2014 Zurich, Switzerland Vita Maria Victoria;
14th Belgian Organic Synthesis Symposium Poster Pd(0)-Catalyzed Enantioselective Synthesis of 1,5-Enynes 13.07.2014 Louvain-la-Neuve, Belgium Vita Maria Victoria;
Swiss Chemical Society - Syngenta Symposium 2013 Poster Direct Azidation of Carbonyl Compounds using a Bench-Stable Hypervalent Iodine Reagent 01.10.2013 Basel, Switzerland Vita Maria Victoria;
Swiss Chemical Society Fall Meeting Poster Direct Azidation of Carbonyl Compounds using a Bench-Stable Hypervalent Iodine Reagent 13.09.2013 Lausanne, Switzerland Vita Maria Victoria;
Swiss Summer School in Synthesis and Catalysis Poster Direct Azidation of Carbonyl Compounds using a Bench-Stable Hypervalent Iodine Reagent 25.08.2013 Villars, Switzerland Vita Maria Victoria;
14th Tetrahedron Symposium Poster Direct Azidation of Carbonyl Compounds using a Bench-Stable Hypervalent Iodine Reagent 25.06.2013 Vienna, Austria Waser Jérôme; Vita Maria Victoria;
Swiss Chemical Society Fall meeting Poster Ethynyl BenziodoXolone (EBX) as reagent for the Metal-Free Ethynylation of Stabilized Enolates 09.09.2011 Lausanne, Switzerland Fernandez Gonzalez Davinia; Waser Jérôme;


Awards

Title Year
SCS-SCNAT ChemistryTravel Award 2014
Werner Prize of the Swiss Chemical Society 2014
Best Poster Presentation Award, 14th Tetrahedron Symposium 2013
Best Poster Presentation Award, Swiss Summer Shool in Catalysis and Synthesis 2013
Prix A. F. Schläfli 2011 of the Swiss Academy of Sciences 2011

Associated projects

Number Title Start Funding scheme
119810 New Catalytic C-C Bond Forming Reactions 01.06.2008 Project funding (Div. I-III)
159920 Multi-Functionalization and Domino Reactions for Accessing Molecular Complexity 01.06.2015 Project funding (Div. I-III)

Abstract

During the last century, synthetic organic chemistry has reached a high level of sophistication. The design of molecules can now been done on the molecular level, and synthetic organic compounds have become increasingly important for the study of biological systems, the cure of illnesses and the discovery of new organic materials. With the development of these applications and the understanding gained in them, the efficient synthesis of complex molecules has become even more important. Despite the great success of the last decades, organic chemistry is still a very time-consuming and expensive process. These difficulties limit applications to simple molecules that are easier to access, but probably not optimal for their intended task. In this context, it is absolutely essential to develop new synthetic tools to increase the flexibility and efficiency of organic synthesis.In the last three years, our research has focused mostly on the discovery of new reactions for the synthesis of acetylenes. The choice of this research topic was motivated by the importance of alkynes, not only in synthesis, but also in biochemistry and materials science. Nevertheless, acetylene transfer reactions usually involve the reaction of acetylides with electrophiles, which limits the number of structures accessible. The discovery in our group of the exceptional properties of ethynyl benziodoxolones (EBX) as electrophilic acetylene synthons (Umpolung of the normal reactivity) allowed the development of new reactions, such as the ethynylation of linear keto, nitro and cyano esters, the oxyalkynylation of olefins and the direct alkynylation of heterocycles.Although very useful building blocks were accessed, the obtained products were racemic. The synthesis of enantiopure compounds is of primordial importance for their bioactivity. The main goal of this proposal renewal is the development of asymmetric alkynylation methods of enolates, based on the following approaches:-Asymmetric phase-transfer, dual activation or enamine catalysis.-The use of other asymmetric methods starting from racemic alkynylation products.The use of the obtained enantiopure products for the synthesis of important building blocks, such as bicyclic carbo- and heterocycles, non-natural amino acids and electrophilic allenes will then be studied. These compounds are important in medicinal and biological chemistry, but the incorporation of chiral quaternary centers in their structure constitutes an important challenge, that cannot be met by classical acetylide chemistry.In parallel to this research project, our studies on the alkynylation of olefins and C-H bonds will also continues, as well as the design and synthesis of new hypervalent iodine reagents for the transfer of other functional groups, in particular azides. The availability of more efficient methods for the Umpolung of acetylenes and azides will increase their utility, not only in organic synthesis, but also for applications in biochemistry and materials science.
-