Etienne J. Donckele

PhD Student


Location: HCI G-314
Phone: +41-44-63-24474
Email:
Etienne J. Donckele

Education

2006–2008: Higher National Diploma in Chemistry, Institute of Technology, Rouen, France
2008: Student assistant at Université du Québec à Montréal (UQAM) with Prof. D. Chapdelaine, Canada
2008–2012: BSc and “diplome d’ingénieur” in Chemistry and Process Engineering, CPE Lyon, France
2009: Internship at Procter&Gamble, Amiens, France
2010–2011: Visiting Scholar at the Broad Institute of MIT and Harvard, Cambridge, MA, USA
2010–2011: Harvard Extension School in Cancer Biology and Organic Chemistry, Harvard University, Cambridge, MA, USA
2011–2012: MSc in Molecular and Biological Chemistry at Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland
2012: Master Thesis with Prof. Barry M. Trost at Stanford University, CA, USA
Since 2013: PhD student with Prof. F. Diederich at ETH Zürich, Switzerland

Expanding the Chemical Space: Towards Novel Reactions for the Design of New Push–Pull Chromophores and Drug-like Molecules

There is a constant need in the chemical and pharmaceutical industries to increase molecular complexity, and the most atom-economic processes to achieve this are those that form more than one bond at the same time.

Adducts of electron-rich alkynes and electron-deficient olefinic compounds, generated via a formal [2+2] cycloaddition–cycloelectrocyclization, are a fascinating class of organic, nonplanar, push–pull chromophores. The optoelectronic properties of this class of compounds are unique for their small size.

For instance, the reaction of electrophilic 2-(dicyanomethylene)indan-1,3-dione (DCID) with substituted, electron-rich alkynes provides two classes of push–pull chromophores with interesting optoelectronic properties. The formal [2+2] cycloaddition–retroelectrocyclization reaction at the exocyclic double bond of DCID gives cyanobuta-1,3-dienes, and the formal [4+2] hetero-Diels–Alder (HDA) reaction at an enone moiety of DCID generates fused 4H-pyran heterocycles. In view of the interest in 4H-pyran derivatives in natural products and biologically active compounds as well as in optoelectronics. Both products can be obtained in good yield and excellent selectivity by carefully tuning the reaction conditions; in particular, the use of Lewis acids dramatically enhances formation of the HDA adduct.

Synthetic Scheme

By replacing the cyano groups in TCNE by ester moieties to afford tetrasubstituted electron-deficient alkenes, the reactivity of the olefin decreased substantially and product and other reaction channels became competitive. In addition to the expected products from the CA–RE and a hetero-Diels–Alder reaction a formal [3+2] cycloaddition–rearrangement cascade reaction. Post-functionalization of those derivatives leads to potential biologically active molecules against malaria, anti-inflammatory or cancer drugs.

Synthetic Route to Heterocycles

Publications

  1. T. A. Reekie,* E. J. Donckele,* G. Maneti, S. Püntener, N. Trapp, F. Diederich, Org. Lett. 2016, 18, 2252–2255. A Three-Step Synthesis of Tetrasubstituted NH-Pyrroles.
  2. E. J. Donckele, T. A. Reekie, N. Trapp, F. Diederich, Eur. J. Org. Chem. 2016, 7264–7275. Penta-2,4-dien-1-ones by Formal [3+2] Cycloaddition–Rearrangement of Electron-Deficient Diethyl 2-(Dicyanomethylene)malonate with Alkynes.
  3. T. A. Reekie, E. J. Donckele, L. Ruhlmann, C. Boudon, N. Trapp, F. Diederich, Eur. J. Org. Chem. 2015, 7264–7275. Ester-Substituted Electron-Poor Alkenes for the Cycloaddition–Retroelectrocyclization (CA–RE) and Related Reactions.
  4. E. J. Donckele, A. D. Finke, L. Ruhlmann, C. Boudon, N. Trapp, F. Diederich, Org. Lett. 2015, 17, 3506–3509. The [2+2] Cycloaddition–Retroelectrocyclization and [4+2] Hetero-Diels–Alder Reaction of 2-(dicyanomethylene)indan-1,3-dione (DCID) with Electron-Rich Alkynes: Influence of Lewis Acids on Reactivity.
  5. B. M. Trost, E. J. Donckele, D. A. Thaisrivongs, M. Osipov, J. T. Masters, J. Am. Chem. Soc. 2015, 137, 2776–2784. A New Class of Non-C2-Symmetric Ligands for Oxidative and Redox-Neutral Palladium-Catalyzed Asymmetric Allylic Alkyation of 1,3-Diketones.
  6. E. J. Donckele, O. Gidron, N. Trapp, F. Diederich, Chem. Eur. J. 2014, 20, 9558–9566. Outstanding Chiroptical Properties: A Signature of Enantiomerically Pure Alleno-Acetylenic Macrocycles and Monodisperse Acyclic Oligomers (cover page).
  7. A. R. Germain, L. C. Carmody, P. P. Nag, B. Morgan, L. VerPlank, C. Fernandez, E. Donckele, Y. Feng, J. R. Perez, S. Dandapani, M. Palmer, E. S. Lander, P. B. Gupta, S. L. Schreiber, B. Munoz, B. Bioorg. Med. Chem. Let. 2013, 23, 1834–1838. Cinnamides as selective small-molecule inhibitors of a cellular model of breast cancer stem cells.
  8. B. M. Trost, D. A. Thaisrivongs, E. J. Donckele, Angew. Chem. 2013, 125, 1563–1566; Angew. Chem. Int. Ed. 2013, 52, 1523–1526. Palladium-Catalyzed Enantioselective Allylic Alkylations via C–H Activation.
  9. B. Gerard, M. W. O’Shea, E. Donckele, S. Kesavan, L. B. Akella, H. Xu, E. N. Jacobsen, L. A. Marcaurelle, ACS Comb. Sci. 2012, 14, 621–630. Application of a Catalytic Povarov Reaction using Chiral Ureas to the Synthesis of Tetrahydroquinoline Library.
  10. J. T. Lowe, M.D. Lee, L. B. Akella, E. Davoine, E. J. Donckele, L. Durak, J. R. Duvall, B. Gerard, E. B. Holson, A. Joliton, S. Kesavan, B. C. Lemercier, H. Liu, J. C. Marié, C. A. Mulrooney, G. Muncipinto, M. W. O’Shea, L. M. Panko, A. Rowley, B. C. Suh, M. Thomas, F. F. Wagner, J. Wei, M. A. Foley, and L. A. Marcaurelle, J. Org. Chem. 2012, 77, 7187–7211. Synthesis and Profiling of a Diverse Collection of Azetidine-Based Scaffolds for the Development of CNS-Focused Lead-Like Libraries.

Patents

  1. A. Germain, B. Munoz, T. A. Lewis, A. Ting, W. Youngsaye, P. P. Nag, C. Dockendorff, C. V. Fernandez, E. Donckele, B. Morgan, E. M. Skoda, B.-C Shu. 2013, WO2013032907 (A1). Compounds and Methods for the Treatment of Cancer Stem Cells.


Last update: September 2016