Neue metallorganische Funktionalisierung von Heterozyklen

• Antragsteller: Professor Dr. Paul Knochel
• Fachliche Zuordnung: Organische Molekülchemie - Synthese, Charakterisierung
• Förderung: Förderung von 2006 bis 2011
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 33545288

• Erstellungsjahr: 2011

Zusammenfassung der Projektergebnisse

Wir haben eine Reihe neuer synthetischer Methoden entwickelt, die metallorganische Intermediate verwenden. Diese Methoden erlauben es, eine breite Palette von heterozyklischen Verbindungen zu synthetisieren. Diese Arbeiten haben eine große Resonanz bei der Pharma-Industrie gefunden: aktuelle (2011) Kooperationen finden zurzeit in unseren Laboratorien statt, welche auf Arbeiten basieren, die in diesem Bericht beschrieben sind.

Projektbezogene Publikationen (Auswahl)

• Efficient Synthesis of Functionalized Organozinc Compounds by the Direct Insertion of Zinc into Organic Iodides and Bromides. Angewandte Chemie International Edition, Vol. 45. 2006, Issue 36, pp. 6040–6044.
  Krasovskiy, A.; Malakhov, V.; Gavryushin, A.; Knochel, P.
  
• Selective Functionalization of Imidazoles via an Iodine-Copper Exchange Reaction. Chemical Communications, Vol. 20. 2006, pp. 2170-2172.
  Yang, X.; Knochel, P.
  
• Direct Aminoalkylation of Arenes and Hetarenes via Ni- Catalyzed Negishi Cross-Coupling Reactions. Organic Letters, Vol. 9. 2007, Issue 26, pp. 5529–5532.
  Melzig, L.; Gavryushin, A.; Knochel, P.
  
• Directed Ortho Insertion (DoI): A New Approach to Functionalized Aryl and Heteroaryl Zinc Reagents. Journal of the American Chemical Society, Vol. 129. 2007, Issue 41, pp. 12358-12359.
  Boudet, N.; Sase, S.; Sinha, P.; Liu, C.-Y.; Krasovskiy, A.; Knochel, P.
  
• Multiple Regioselective Functionalizations of Quinolines via Magnesiations. Organic Letters, Vol. 9. 2007, Issue 26, pp. 5525-5528.
  Boudet, N.; Lachs, J. R.; Knochel, P.
  
• An Efficient Silane-Promoted Nickel-Catalyzed Amination of Aryl and Heteroaryl Chlorides. Journal of Organic Chemistry, Vol. 73. 2008, Issue 4, pp. 1429-1434.
  Manolikakes, G.; Gavryushin, A.; Knochel, P.
  
• High Temperature Metalation of Functionalized Aromatics and Heteroaromatics using (tmp)2Zn·2MgCl2 2LiCl and Microwave Irradiation. Organic Letters, Vol. 10. 2008, Issue 20, pp. 4705-4707.
  Wunderlich, S.; Knochel, P.
  
• Multiple Regio- and Chemoselective Functionalizations of Pyrimidine Derivatives Using TMPMgCl·LiCl and TMP2Mg·2LiCl. Synthesis, Vol. 22. 2008, pp. 3697-3702.
  Mosrin, M.; Petrera, M.; Knochel, P.
  
• Polyfunctionalizations of N-Heterocycles via Chemo- and Regioselective Metalations, Dissertation, Fakultät für Chemie und Pharmazie der Ludwig-Maximilians-Universität München, 2008.
  Nadège Boudet
  
• 2,3-Functionalization of Furans, Benzofurans and Thiophenes via Magnesiation and Sulfoxide-Magnesium Exchange. Chemical Communications, Vol. 24. 2009, pp. 3536-3538.
  Melzig, L.; Rauhut, C B.; Knochel, P.
  
• Br/Mg-Exchange on 1,2-Dibromocyclopentene Derivatives and Regioand Chemoselective Functionalizations of Pyrazoles and Related Heterocycles. Dissertation, LMU, Fakultät für Chemie und Pharmazie, München 2009.
  Christina Despotopoulou
  
• Directed Manganation of Functionalized Arenes and Heterocycles Using tmp2Mn·2MgCl2·4LiCl. Angewandte Chemie International Edition, Vol. 48. 2009, Issue 39, pp. 7256–7260.
  Wunderlich, S. H.; Kienle, M.; Knochel, P.
  
• Functionalization of 4,5-Dihydrobenzo[g]indazoles Using Magnesium- or Zinc-Heterocyclic Intermediates. Synthesis, Vol. 21.2009, pp. 3661-3671.
  Despotopoulou, C.; Gignoux, C.; McConnell, D.; Knochel, P.
  
• High Temperature Zincation of Functionalized Aromatics and Heteroaromatics Using TMPZnCl.LiCl and Microwave Irradiation. Chemical Communications, Issue 37. 2009, pp. 5615-5617.
  Mosrin, M.; Monzon, G.; Bresser, T.; Knochel, P.
  
• New Mixed Li/Mg and Li/Mg/Zn Amides for the Chemoselective Metalation of Arenes and Heteroarenes. European Journal of Organic Chemistry, Special Issue: Dedicated to Professor Alain Krief, Vol. 2009, Issue 11, pp. 1781–1795.
  Rohbogner, C. J.; Wunderlich, S. H.; Clososki, G. C.; Knochel, P.
  
• Atom-Economical Preparation of Aryl- and Heteroaryl-Lanthanum Reagents by Directed ortho-Metalation by Using tmp3[La]. Chemistry - A European Journal, Vol. 16. 2010, Issue 11, pp. 3304–3307.
  Wunderlich, S. H.; Knochel, P.
  
• Fischer Indole Synthesis with Organozinc Reagents. Angewandte Chemie International Edition, Vol. 49. 2010, Issue 49, pp. 9513–9516.
  Haag, B. A.; Zhang, Z.-G.; Li, J.-S.; Knochel, P.
  
• Phosphorodiamidate-Directed Metalation of NHeterocycles using Mg- and Zn-TMP Bases. Organic Letters, Vol. 12. 2010, Issue 9, pp. 1984–1987
  Rohbogner, C. J.; Wirth, S.; Knochel,
  
• Regio- and Chemoselective Zincation of Sensitive and Moderately Activated Aromatics and Heteroaromatics Using TMPZnCl·LiCl. Journal of Organic Chemistry, Vol. 75.2010, Issue 14, pp. 4686–4695.
  Bresser, T.; Mosrin, M.; Monzon, G.; Knochel, P.
  
• TMP2Mg·2LiCl and Related Bases for the Metalation of Unsaturated Substrates and the Role of the Phosphorodiamidate Directing Group. A new Cobalt-Catalyzed Sulfonate/Copper-Exchange. Dissertation, LMU München: Fakultät für Chemie und Pharmazie, 2010.
  Christoph Rohbogner