Dissertation zur Erlangung des Doktorgrades der Fakultät für Chemie und Pharmazie der Ludwig-Maximilians-Universität München New Preparation of Organoaluminiums – Catalysed Metal Insertion of Aluminium Powder and Synthetic Applications of Organoalanes - Preparation of 1,2-Bimetallics by Direct Insertion of Aluminium or Zinc Powder von Tobias Daniel Blümke aus Starnberg, Deutschland 2012 Erklärung Diese Dissertation wurde im Sinne von §7 der Promotionsordnung vom 28. November 2011 von Herrn Prof. Dr. Paul Knochel betreut. Eidesstattliche Versicherung Diese Dissertation wurde eigenständig und ohne unerlaubte Hilfe erarbeitet. München, am 15. Juni 2012 …..…………………………………… Tobias Blümke Dissertation eingereicht am 18.06.2012 1. Gutachter: Prof. Dr. Paul Knochel 2. Gutachter: Prof. Dr. Konstantin Karaghiosoff Mündliche Prüfung am 13.07.2012 This work was carried out from March 2009 to June 2012 under the guidance of Prof. Dr. Paul Knochel at the Department Chemie of the Ludwig-Maximilians-Universität, Munich. Firstly, I would like to express my appreciation to Prof. Dr. Paul Knochel for giving me the great opportunity to do my PhD in his group and for his guidance and support in the course of my scientific research. I am also very grateful to Prof. Dr. Konstantin Karaghiosoff for agreeing to be my “Zweitgutachter”, as well as Prof. Dr. Manfred Heuschmann, Prof. Dr. Konrad Koszinowski, Prof. Dr. Klaus T. Wanner and Prof. Dr. Heinz Langhals for their interest shown in this manuscript by accepting to be referees. I really would like to thank Annette Frischmuth, Veronika Werner, Andreas Unsinn and Klaus Groll for the careful correction of this manuscript. I thank all past and present co-workers I have met in the Knochel group for their kindness and their help. Special thanks to my actual and former lab mates Yi- Hung Chen, Albrecht Metzger, Milica Jaric, Stéphanie Duez, Sophia Manolikakes, Nadja Barl und Julia Nafe for the great music, the motivating atmosphere and the great times we had. Special thanks to my bench-neighbours Milica and Naddl for coping with me and my temper when aluminium drove me crazy once in a while. I’d like to thank Yi-Hung Chen for the best collaboration of my life and for his extraordinary good mood as well as Klaus Groll, Zhihua Peng and Thomas Klatt for the fruitful collaborations. Thanks to Konstantin Karaghiosoff for wasting night after night trying to make the aluminium bearing carbon atom visible. Thanks to Konrad Koszinowski for the fruitful ESI collaboration and his help during my scientific work. A huge acknowledgement to my students Andrej Angelowski, Veronique Paulus, Matthias Westphal und Yvonne Morgenstern for their excellent work and highly valuable contributions to this work during their internship in the Knochel group. Moreover, I have to thank, Matthias Schade for the endless discussions about chemistry, life in general and for teaching me what a real snorer is. Special thanks to Sebastian Bernhardt for all the great times we had in and out of university. Thanks to Klaus Groll for keeping up the frustrating work and for pushing me, exactly in the right moments, with the right words. Sincere props to the old BUTNAD crew for endless discussions and for the help in impressing my doc with my increased liver values. Special thanks to Andreas Unsinn, Andreas Wagner, Christoph Sämann, and Gabriel “Hombre” Monzon without you it would not have been as nice. A huge “thanks” to Thomas Kunz for EVERYTHING and for his enduring friendship throughout the last 10 years. Thanks to everybody who supported me during the last years - you know who you are and you know what you did. I would also like to thank Dr. Vladimir Malakhov, Simon Matthe, and Yulia Tsvik for their help in organizing everyday life in the lab and in the office, as well as the analytical team of the LMU for their invaluable help. Very special thanks to Renate Schröder, the best secretary in the world, for her invaluable help, support, her calm and cool attitude and her support throughout the years. Very special thanks to my family for their great support, throughout my studies, my PhD and all the rest of my life. Endless thanks to Annette for her patience throughout the years, her support and love and for too much to be mentioned here. EOF Parts of this PhD Thesis have been published: PUBLICATIONS 1. Tobias Blümke, Yi-Hung Chen, Zhihua Peng, Paul Knochel, “Preparation of Functionalized Organoaluminiums by Direct Insertion of Aluminium to Unsaturated Halides”, Nature Chemistry, 2010, 2, 313-318. (Highlighted in: Synfacts 2010, 705) 2. Zhihua Peng, Tobias D. Blümke, Peter Mayer, Paul Knochel, “Diastereoselective Synthesis of Homoallylic Alcohols with Adjacent Tertiary and Quaternary Centers Using New Functionalized Allylic Aluminum Reagents”, Angew. Chem. 2010, 45, 8695-8698; Angew. Chem. Int. Ed. 2010, 49, 8516-8519. 3. Tobias D. Blümke, Klaus Groll, Konstantin Karaghiosoff, Paul Knochel, “New Preparation of Benzylic Aluminum and Zinc Organometallics by Direct Insertion of Aluminum Powder”, Org. Lett. 2011, 13, 6440. 4. Tobias D. Blümke, Thomas Klatt, Konrad Koszinowski, Paul Knochel, „InCl3-Catalyzed Preparation of 1,2-Bimetallics by Direct Insertion of Al and Zn Powder“, Angew. Chem., submitted. 5. Klaus Groll, Tobias D. Blümke, Andreas Unsinn, Diana Haas, Paul Knochel, “Direct Pd- catalyzed Cross-Coupling of Functionalized Organoaluminum Reagents”, manuscript in preparation. PATENTS 1. Yi-Hung Chen, Tobias D. Blümke, Paul Knochel, „Process for preparation of functionalized substituted biaryls and allylarenes by cross-coupling of aryl and allyl halides with arylaluminum compounds mediated by metal halides”. PCT Int. Appl. (2011), WO 2011023791 A2 20110303. BOOK CHAPTERS 1. Paul Knochel, Tobias Blümke, Klaus Groll, Yi-Hung Chen, “Preparation of Organoalanes for organic synthesis”, Topics in Organometallic Chemistry – The Al volume (Ed. S. Woodward, S. Dagorne), Springer, 2012, submitted. POSTER PRESENTATIONS 1. Klaus Groll, Tobias D. Blümke, Paul Knochel, “Direct Insertion of Aluminum Powder Into Unsaturated Halides and Subsequent Functionalizations”, BASF CaRLa Winterschool, 06. - 12.03.2010, Heidelberg, Germany. Meiner Familie Da steh ich nun, ich armer Tor! Und bin so klug als wie zuvor. -Faust- A. INTRODUCTION ................................................................................................................................................. 1 1 OVERVIEW ........................................................................................................................................................ 2 1.1 Organometallic Chemistry .................................................................................................................... 3 1.2 Organoaluminium Chemistry ............................................................................................................... 4 1.3 Preparation methods of Organoaluminium Compounds ................................................................ 5 2 MOTIVATION AND OBJECTIVES .................................................................................................................13 B. RESULTS AND DISCUSSION ...........................................................................................................................15 1 CATALYSED ALUMINIUM INSERTION INTO ARYL HALIDES ................................................................16 1.1 Abstract ..................................................................................................................................................16 1.2 Introduction ..........................................................................................................................................16 1.3 Preparation of Aryl Aluminium Sesquihalides .................................................................................17 2 CATALYSED ALUMINIUM INSERTION INTO BENZYLIC HALIDES .......................................................32 2.1 Abstract ..................................................................................................................................................32 2.2 Introduction ..........................................................................................................................................32 2.3 Preparation of Benzylic Aluminium Sesquichlorides......................................................................33 2.4 Preparation of Bis-Benzylic Organometallics ..................................................................................39 2.5 NMR Studies of the Transmetallation of Aluminium Reagents using Zn-Salts ........................43 3 DIASTEREOSELECTIVE ADDITION OF ALLYLIC ALUMINIUM REAGENTS TO ALDEHYDES AND KETONES .................................................................................................................................................................50 3.1 Abstract ..................................................................................................................................................50 3.2 Introduction ..........................................................................................................................................50 3.3 InCl3-Catalysed Insertion of Aluminium to Allylic Halides ..........................................................51 3.4 Tolerance of Acidic Protons – Addition to Carbonyls in the Presence of Unprotected Phenols .................................................................................................................................................................57