Momcilo Miljkovic Electrostatic and Stereoelectronic E ects in Carbohydrate Chemistry Electrostatic and Stereoelectronic Effects in Carbohydrate Chemistry Momcilo Miljkovic Electrostatic and Stereoelectronic Effects in Carbohydrate Chemistry Momcilo Miljkovic Pennsylvania State University Hershey, Pennsylvania, USA ISBN 978-1-4614-8267-3 ISBN 978-1-4614-8268-0 (eBook) DOI 10.1007/978-1-4614-8268-0 Springer New York Heidelberg Dordrecht London Library of Congress Control Number: 2013955044 © Springer Science+Business Media New York 2014 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) To the memory of my parents Prof. Dr. Adam Miljkovic´ and Dr. Dragoslava Miljkovic´ In Memoriam Dr. Momcilo Miljkovic was born on December 12, 1931, in Belgrade, Serbia. He was the son of physicians Dr. Adam Miljkovic and Dr. Dragoslava Miljkovic. At the age of 14, his father bought him a chemistry kit, and soon Momcilo was passionately conducting chemistry experiments at home in the family’s kitchen. He became completely fascinated with chemistry, reading college textbooks while still in high school, and developing a reputation as a young chemist, so much so that his chemistry teacher would look to him in class for his approval or disapproval regarding the correctness of her lectures. Dr. Momcilo Miljkovic went on to pursue a B.S. in chemistry at The University of Belgrade, Serbia, and later was awarded a Ph.D. in Chemistry in 1965 at the Eidgenossische Technische Hochschule (Swiss Federal Institute of Technology) in Zurich, Switzerland. He pursued post-doctoral studies under Dr. Vladimir Prelog (Nobel Laureate) at ETH, while his informal mentor was Dr. Leopold Ruzicka (Nobel Laureate). Another post-doctoral position brought him to the United States to the Depart- ment of Biochemistry at Duke University, and a year later he took a position as Assistant Professor in The Department of Biochemistry in the College of Medicine at The Pennsylvania State University. It is here that he spent over 40 years of his life, conducting research in carbohydrate chemistry as well as teaching graduate students and medical students. Towards the end of his life, he preoccupied himself with writing. He published his first book Carbohydrates: Synthesis, Mechanisms, and Stereoelectronic Effects in 2010. He was particularly excited about writing Electrostatic and Stereoelectronic Interactions in Carbohydrate Chemistry due to the novelty of the material. Further, writing helped him focus away from his own terminal illness, giving him a newfound purpose in the latter stages of his life. vii Acknowledgments Several details were left unfinished, and completed after the author’s death. Without the time, effort, and expertise of Dr. Stephen Benkovic, Department of Chemistry at The Pennsylvania State University, in editing portions of this book, it could not have been published. Nor would this book have seen the light of day without the cheerful persistence of Dr. Marko Miljkovic´, who nursed his father through his final illness, sorted through manuscripts left by his father, consulted with carbohydrate chemists when details in the manuscript were unclear, and meticulously edited portions of this book. ix Contents 1 Introduction ........................................... 1 1.1 Intramolecular Electrostatic Interactions ................... 1 References . 9 2 Anomeric Effect and Related Stereoelectronic Effects ........... 11 2.1 Exo-Anomeric Effect . .............................. 19 2.2 Generalized Anomeric Effect . 21 2.3 Reverse Anomeric Effect . ............................ 24 2.4 Anomeric Effect in Systems O–C–N . ................... 39 2.5 Gauche Effect . .................................... 43 References . 45 3 Oxocarbenium Ion ...................................... 51 3.1 Acid-Catalyzed Hydrolysis of Glycosides .................. 51 3.2 The Acid-Catalyzed Hydrolysis of Glycopyranosides . ......... 54 3.3 Acid-Catalyzed Hydrolysis of Glycofuranosides .............. 61 3.4 Some Recent Developments Regarding the Mechanism of Glycoside Hydrolysis . ............................ 65 3.5 Acetolysis of Glycosides ............................... 71 References . 82 4 Conformations and Chemistry of Oxocarbenium Ion ............ 87 References . 110 5 Armed-Disarmed Concept in the Synthesis of Glycosidic Bond ...................................... 117 5.1 Stereoelectronic Effects of Substituents: Polyhydroxylated Piperidines and Sugars . .................. 125 5.2 Glycosylation Reactions with Conformationally Armed Glycosyl Donors ............................... 131 xi xii Contents 5.3 Superarmed Glycosyl Donors in Glycosylation Reactions . 133 5.3.1 Regio- and Stereoselectivity in Glycosylation . 141 5.3.2 Proton-Catalyzed Addition of Alcohols to Glycals: Glycals as Glycosyl Donors . 154 References . 169 6 Stereoelectronic Effects in Nucleosides and Nucleotides .......... 181 References . 189 7 Free Radical Cyclizations ................................. 197 References . 218 8 Carbohydrate Sulfones ................................... 225 8.1 Michael Additions to Vinyl Sulfones ...................... 225 8.2 Glycosyl Sulfones . 235 8.3 Strecker Reaction . 240 8.4 Mercuration of Carbohydrate Olefins . .......... 244 8.5 1,3-Dipolar Cycloaddition of Chiral N-(Alkoxyalkyl) Nitrones ........................................... 247 8.5.1 Synthesis of Glycosides by Reduction of Sugar Orthoesters . ................................. 250 8.6 Reductive Cleavage of Glycosidic Bond . ................. 263 8.7 Carbohydrate Degradation by Oxygen ..................... 269 8.8 Norrish-Yang Photocyclization . 271 References . 277 Author Index ............................................. 285 Subject Index ............................................. 303 Chapter 1 Introduction Stereoelectronic interactions in a molecule are important because they determine the conformation of that molecule and thus its chemical reactivity and very often the stereochemistry of its chemical transformations. These interactions involve the orbital interactions between the nonbonding orbitals. The presence of charged or partially charged atoms (dipoles) in a molecule generates electrostatic interactions. These interactions can take place between two or more such molecules (intermolecular electrostatic interactions) or can be within a single molecule (intramolecular electrostatic interactions). The electrostatic inter- actions can be stabilizing or destabilizing in nature: When two opposing charges are facing each other or are next to each other, they are stabilizing, and when two identical charges are facing each other or are next to each other, they are destabilizing. The intermolecular electrostatic interactions are found in bimolecular reactions of a charged reactant approaching a molecule with strong dipolar bonds or even charges (e.g., in enzyme-catalyzed reactions, where they are used not only to properly position a substrate in the active site of an enzyme but also to lower the activation energy barrier for the subsequent chemical transformation of a substrate). The intramolecular electrostatic interactions play a very important role in the control of the conformation of a molecule and consequently control its chemical behavior. These interactions will be discussed first. 1.1 Intramolecular Electrostatic Interactions In 1953, Corey [1] studied the conformational equilibrium of α-halocyclohexanones (α-bromo- and α-chlorocyclohexanones) since the C¼O and the C–X (X ¼ halo- gen) bonds are both strongly polarized, mutually repulsive, and next to each other. The conformer having the halogen atom equatorially oriented should be destabilized due to dipolar interactions between the C–X and the C¼O dipoles which are almost coplanar and equatorially oriented, whereas the conformer