Hydrogen-bonded Capsules Molecular Behavior in Small Spaces 9605hc_9789814678353_tp.indd 1 6/7/15 3:48 pm May2,2013 14:6 BC:8831-ProbabilityandStatisticalTheory PST˙ws TThhiiss ppaaggee iinntteennttiioonnaallllyy lleefftt bbllaannkk Hydrogen-bonded Capsules Molecular Behavior in Small Spaces Julius Rebek, Jr. Fudan University, China & The Scripps Research Institute, USA World Scientific NEW JERSEY • LONDON • SINGAPORE • BEIJING • SHANGHAI • HONG KONG • TAIPEI • CHENNAI • TOKYO 9605hc_9789814678353_tp.indd 2 6/7/15 3:48 pm Published by World Scientific Publishing Co. Pte. Ltd. 5 Toh Tuck Link, Singapore 596224 USA office: 27 Warren Street, Suite 401-402, Hackensack, NJ 07601 UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE Library of Congress Cataloging-in-Publication Data Rebek, Julius, Jr. Hydrogen-bonded capsules : molecular behavior in small spaces / Julius Rebek, Jr., Fudan University, China & The Scripps Research Institute, USA. pages cm Includes bibliographical references and index. ISBN 978-9814678353 (hardcover : alk. paper) -- ISBN 981467835X (hardcover : alk. paper) 1. Nanochemistry. 2. Microencapsulation. 3. Hydrogen bonding. 4. Chemistry, Organic. I. Title. QC176.8.N35R42 2015 541'.2--dc23 2015023647 British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. Copyright © 2016 by World Scientific Publishing Co. Pte. Ltd. All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means, electronic or mechanical, including photocopying, recording or any information storage and retrieval system now known or to be invented, without written permission from the publisher. For photocopying of material in this volume, please pay a copying fee through the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA. In this case permission to photocopy is not required from the publisher. Printed in Singapore SC - Hydrogen-bonded Capsules.indd 1 22/6/2015 9:33:34 AM August27,2015 14:27 Hydrogen-bondedCapsules-9inx6in b2107-fm pagev For Stephen L. Buchwald and Jin-Quan Yu Architects of chemical catalysis v May2,2013 14:6 BC:8831-ProbabilityandStatisticalTheory PST˙ws TThhiiss ppaaggee iinntteennttiioonnaallllyy lleefftt bbllaannkk August27,2015 14:27 Hydrogen-bondedCapsules-9inx6in b2107-fm pagevii Contents Prologue 1 Chapter 1 Spherical and Similar Capsules 3 Chapter 2 Calixarene Capsules 37 Chapter 3 The Cylindrical Capsule 57 Chapter 4 Hexameric Capsules from Resorcinarenes and Pyrogallolarenes 99 Chapter 5 Stereochemistry of Confined Molecules 117 Chapter 6 Chiral Capsules 133 Chapter 7 Expanded and Contracted Capsules 153 Chapter 8 Reactions Inside Capsules 191 Index 219 vii May2,2013 14:6 BC:8831-ProbabilityandStatisticalTheory PST˙ws TThhiiss ppaaggee iinntteennttiioonnaallllyy lleefftt bbllaannkk August27,2015 14:27 Hydrogen-bondedCapsules-9inx6in b2107-prologue page1 Prologue Research on molecular recognition became a fashionable topic for physical organic chemists in the 1980s. At the time there was grow- ingdisenchantmentwiththenonclassicalioncontroversy,andorbital symmetry fatigue was taking hold in the community. But the discov- ery of crown ethers by Pedersen in 1962 ignited the study of their complexeswithions,andmacrocyclicpolyethersdominatedthescene fordecades.Theweakintermolecularinteractionsofthesecomplexes gave rise to the concepts of molecular recognition: complementarity ofsizes,shapesandchemicalsurfaces.Theculminationofthisactivity wastheawardoftheNobelPrizeinChemistrytoPedersen,Cramand Lehnin1987forestablishinghost–guestchemistryand,onagrander scale, supramolecular chemistry. Whilemostpractitionersfavoredmacrocycliccompoundsforthe recognitionofions,therewereseveralgroupswhopursuedreceptors of different shapes for other molecular targets. The shapes included a number of concave surfaces and — in our case — clefts, optimized for the study of reversible interactions. Along with many others, we became proficient in sculpting molecular surfaces to complement the convex surfaces of the small molecular targets. This activity was a departurefromtargetingsphericalionswithcircularreceptors—the low-hangingfruit—sinceneutralmoleculetargetscomeinallmanner ofsizesandshapes.Theapplicationofhydrogenbondingforrecogni- tion purposes offered much appeal and became suspiciously close to thebase-pairingofDNA.Purines,pyrimidinesandotherheterocyclic bases,richinhydrogen-bondingpossibilities,becamepopulartargets. We pursued synthetic receptors that contacted incresingly large frac- tions of surfaces of the target molecules, and it became a reasonable 1