Departm en t of Chem istry Aa lto- Essi Karppanen Karppanen Essi DD 32 C hi r a l 9 -p hen y l-9 H- / 2016 fluoren-9-amines in C hi r a l 9 -p hen y l-9 asymmetric induction Essi Karppanen H -fluoren-9-amines in asymmetric induction induction in asymmetric -fluoren-9-amines 9HSTFMG*aggghh+ 9HSTFMG*aggghh+ ISB N 978 -952-60-6667-7 (pr in ted) B USINESS + ISB N 978 -952-60-6668 -4 (pdf) ECONOMY ISSN-L 1799-493 4 ISSN 1799-493 4 (pr in ted) ART + ISSN 1799-4942 (pdf) DESIGN + ARCHITECTURE Aalto Un iversity Aalto Un iversity School of Chem ical Techn ology SCIENCE + Departm en t of Chem istry TECHNOLOGY www.aalto.fi CROSSOVER DOCTORAL DOCTORAL DISSERTATIONS DISSERTATIONS 2016 "BMUP6OJWFSTJUZQVCMJDBUJPOTFSJFT %0$503"-%*44&35"5*0/4 "#,&ŗăĚ*"(3&ĚăHĚó/),(ĚăĚ'#(-ŗ #(ŗ-3''.,#ŗ#(/.#)(ŗ &TTJ,BSQQBOFO "EPDUPSBMEJTTFSUBUJPODPNQMFUFEGPSUIFEFHSFFPG%PDUPSPG 4DJFODF 5FDIOPMPHZ UPCFEFGFOEFE XJUIUIFQFSNJTTJPOPGUIF "BMUP6OJWFSTJUZ4DIPPMPG$IFNJDBM5FDIOPMPHZ BUBQVCMJD 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I would like to acknowledge and thank Aalto University for the financial support for this work. First, I would like to thank my supervisor Professor Ari Koskinen for all the help, advice and fun times during the years. I truly admire his knowledge on organic chemistry and other fields as well. I also appreciate his encouragement in whatever I might want to pursue, in chemistry or other areas in life. I would also like to thank Professor Petri Pihko, who accepted me as a part of his research group when I was an undergraduate student. I learned a lot of chemistry during that time and I really enjoyed working in the lab. I would like to thank Associate Professor Annette Bayer and Professor Reko Leino for carefully revising this manuscript and providing valuable comments. I am grateful to Dr. Antti Kataja for revising the language of this thesis. I would like to thank our laboratory staff members: Dr. Jari Koivisto for keeping the NMR facilities in shape, Tiia Juhala and Johanna Mareta for the HRMS analyses and Anneli Parvinen for handling all the administrative stuff. I would also like to thank Päivi Joensuu from Oulu University for HRMS analyses and Dr. Martin Nieger from University of Helsinki for crystallographic measurements. I am grateful for Dr. Antti Pohjakallio, who was such a great and inspiring teacher when I first started working in the organic chemistry lab. I would like to thank all the other previous group members and post-docs as well for good times in the lab and of course chemistry related advice and guidance: Esa, Jatta, Laurent, Peter, Katja, Anna and Andreas. Also the newer group members deserve big thanks for contributing to the spirit in the lab: Aino, Saara, Annakaisa, Andrejs and Joel. I would also like to thank undergraduate students Miika, Reetta, Emilia and Lotta for all the help in the lab. I would like to thank Dr. Pekka Joensuu for all kinds of inspiring discussions. I would like to give my warmest thanks to our current group members: Annika, Christopher, Oskari and Antti. We’ve had so much fun during the years, in and outside the lab! Lastly, outside the lab, I want to thank my friends and family for all the love and support. AUTHOR’S CONTRIBUTION The author, Essi Karppanen, designed and carried out the experiments, recorded the analytical data (with exceptions mentioned in the Acknowledgements), and interpreted the results presented in this thesis. Certain parts of the work were done by other researchers in collaboration with the author. The aerobic oxidation catalyst screenings shown in Chapter 10 were designed by Dr. Esa Kumpulainen, and they were carried out by undergraduate student Miika Karjomaa under the supervision of the author. Publications relevant to this thesis were written by the author.3 TABLE OF CONTENTS Abstract Tiivistelmä (Abstract in Finnish) Acknowledgements Author’s contribution Table of contents Abbreviations and symbols 1. Introduction 15 2. Amino acids 17 3. 9-Phenyl-9H-fluoren-9-yl group 19 3.1 Properties of the Pf group 19 3.2 Installation and cleavage of the Pf group 23 4. Phenethylamines 25 4.1 Biological implications of phenethylamines 26 4.2 Biosynthesis and metabolism of phenethylamines 27 4.3 Sympathomimetic phenethylamines 28 4.3.1 Ephedrine 28 4.3.2 Cathinone 28 4.3.3 Mescaline 29 4.3.4 Amphetamine 29 4.3.5 MDMA 30 4.4 Synthetic routes to phenethylamines 31 4.5 L-Dopa 32 4.5.1 Industrial synthesis of L-dopa 33 4.5.2 Other methods to obtain L-dopa 35 5.