Directed Selectivity in Organic Synthesis: A Practical Guide

Bringing together examples that until now were often hidden and widely spread throughout the original literature, this textbook shows how to use the correct reagents, conditions or reaction sequences to have access to all possible stereoisomers when beginning synthesis with only a single starting material. Adopting a didactic approach, the authors have chosen general and simple examples throughout the book so that these reactions can be transferred easily to other reaction types. While of major interest to master and PhD students alike, this book is also a source of valuable information for organic chemists in both academia and industry. Additional material for lectures at www.wiley–vch.de/textbooks

Preface VII Acknowledgement IX 1 General Methods to Direct Selectivity 1 1.1 Chemoselectivity 1 1.2 Regioselectivity 7 1.3 Stereoselectivity 26 1.4 Enatioselectivity 48 References 60 2 Directed Selectivity: Acetylenes and Alkenes 65 2.1 Acetylenes 65 2.2 Alkenes 74 2.2.1 Hydrogenation and Reduction 74 2.2.2 Hydroformylation 81 2.2.3 Oxidation and Allyl Oxidation 84 2.2.4 Allyl Substitution 89 2.2.5 Cycloaddition 110 2.2.6 Sigmatropic Rearrangement 120 2.2.7 Ene Reaction 125 2.2.8 Heck Cyclization 128 2.2.9 Pauson–Khand Reaction 130 2.2.10 Metathesis Cyclization 131 2.2.11 Radical– and Nucleophilic Cyclization 133 References 135 3 Directed Selectivity with Carbonyl Derivatives 141 3.1 Carbonyl Compounds as Electrophiles 141 3.1.1 1,2–Addition of Nucleophiles to Carbonyls 141 3.1.2 Reduction of Carbonyl Compounds 151 3.1.3 Allylation/Crotylation Reactions 163 3.2 Conjugate Addition to Carbonyl Compounds 178 3.2.1 Cuprate Additions 178 3.2.2 Enolate Additions 181 3.2.3 Free Radical Addition to Enoates 182 3.2.4 Olefin Formation by Organometal Addition to Alkynes 184 3.3 Enolate Derivatives 185 3.4 Miscellaneous 194 3.4.1 Rearrangements and Fragmentations 194 3.4.2 Pericyclic Reactions 198 3.4.3 Lewis Acid–Mediated Carbonyl ene Reactions 200 3.4.4 Organometal–Mediated C–C Connections 201 3.4.5 Metal Complex Formation in Carbonyl and Imine Additions 202 3.4.6 Wittig–Type Reactions 205 3.4.7 Oxidation Reactions 207 References 208 4 Selectivity at sp3 –Centers and Heteroatoms 217 4.1 Epoxides 217 4.2 Acetals 249 4.3 Ethers 266 4.4 Alcohols and Phenols 285 4.5 Sulfur Compounds 303 4.6 Amines 318 4.7 Halogen Compounds 334 References 345 Index 355

Ekkehard Winterfeldt received a PhD in 1958 with a dissertation on the total synthesis of lupin alkaloids at the University of Braunschweig. In 1959 he moved to the Technical University Berlin as an Assistant Professor and started to work on his habilitation. The venia legendi was awarded in 1963, and in 1969 he was offered chairs at the University of Marburg, Berlin and Hannover. He joined the Organic Chemistry Department in Hannover in 1970. He is member of the Akademie der Wissenschaften in Göttingen, the Braunschweiger Wissenschaftliche Gesellschaft and the Leopoldina Halle. He received various awards and medals, served as the president of the GDCh and as a senator of the DFG. Since 2000, he is Prof. Emeritus at the Organic Chemistry Department, University Hannover and he was elected an Honorary Member of the GDCh in 2012. Tanja Gaich studied Chemistry and Biology at the University of Salzburg (Austria) and University of Vienna (Austria). After completing her diploma thesis at the University of Vienna in 2005, she received her doctorate degree under the supervision of Prof. Dr. J. Mulzer in 2009 from the University of Vienna. She then conducted a postdoctoral research at the Scripps Research Institute with Prof. Dr. Phil S. Baran. In 2010, she started her independent academic career at the Leibniz University of Hannover, supported by the Alexander von Humboldt Foundation with a Sofja Kovalevskaja prize.