Arrow Pushing in Inorganic Chemistry : a Logical Approach to the Chemistry of the Main Group ElementsAbhik Ghosh, Steffen Berg
Involved as it is with 95% of the periodic table, inorganic chemistry is one of the foundational subjects of scientific study. Inorganic catalysts are used in crucial industrial processes and the field, to a significant extent, also forms the basis of nanotechnology. Unfortunately, the subject is not a popular one for undergraduates. This book aims to take a step to change this state of affairs by presenting a mechanistic, logical introduction to the subject.
Organic teaching places heavy emphasis on reaction mechanisms - "arrow-pushing" - and the authors of this book have found that a mechanistic approach works just as well for elementary inorganic chemistry. As opposed to listening to formal lectures or learning the material by heart, by teaching students to recognize common inorganic species as electrophiles and nucleophiles, coupled with organic-style arrow-pushing, this book serves as a gentle and stimulating introduction to inorganic chemistry, providing students with the knowledge and opportunity to solve inorganic reaction mechanisms.
• The first book to apply the arrow-pushing method to inorganic chemistry teaching
• With the reaction mechanisms approach ("arrow-pushing"), students will no longer have to rely on memorization as a device for learning this subject, but will instead have a logical foundation for this area of study
• Teaches students to recognize common inorganic species as electrophiles and nucleophiles, coupled with organic-style arrow-pushing
• Provides a degree of integration with what students learn in organic chemistry, facilitating learning of this subject
• Serves as an invaluable companion to any introductory inorganic chemistry textbook
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Arrow Pushing in Inorganic Chemistry Arrow Pushing in Inorganic Chemistry A Logical Approach to the Chemistry of the Main-Group Elements Abhik Ghosh Steffen Berg Copyright © 2014 by John Wiley & Sons, Inc. All rights reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. 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Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com. Library of Congress Cataloging-in-Publication Data is available. ISBN: 978-1-118-17398-5 Printed in the United States of America 10 9 8 7 6 5 4 3 2 1 Contents FOREWORD xi PREFACE xiii ACKNOWLEDGMENTS xvii 1. A Collection of Basic Concepts 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 Nucleophiles and Electrophiles: The SN 2 Paradigm What Makes for a Good Nucleophile? Hard and Soft Acids and Bases: The HSAB Principle pKa Values: What Makes for a Good Leaving Group? Redox Potentials Thermodynamic Control: Bond Dissociation Energies (BDEs) Bimolecular 𝛽-Elimination (E2) Proton Transfers (PTs) Elementary Associative and Dissociative Processes (A and D) Two-Step Ionic Mechanisms: The SN 2-Si Pathway Two-Step Ionic Mechanisms: The SN 1 and E1 Pathways Electrophilic Addition to Carbon–Carbon Multiple Bonds Electrophilic Substitution on Aromatics: Addition–Elimination Nucleophilic Addition to Carbon–Heteroatom Multiple Bonds Carbanions and Related Synthetic Intermediates Carbenes Oxidative Additions and Reductive Eliminations 1 2 5 8 9 11 11 14 15 16 19 20 22 23 24 26 29 30 Sections marked with an asterisk (*) may be skipped on first reading. v vi CONTENTS 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 Migrations Ligand Exchange Reactions Radical Reactions Pericyclic Reactions Arrow Pushing: Organic Paradigms Inorganic Arrow Pushing: Thinking Like a Lone Pair Definitions: Valence, Oxidation State, Formal Charge, and Coordination Number Elements of Bonding in Hypervalent Compounds The 𝜆 Convention The Inert Pair Effect Summary Further Reading 2. The s-Block Elements: Alkali and Alkaline Earth Metals 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Solubility The s-Block Metals as Reducing Agents Reductive Couplings Dissolving Metal Reactions Organolithium and Organomagnesium Compounds Dihydrogen Activation by Frustrated Lewis Pairs (FLPs) A MgI –MgI Bond Summary Further Reading 3. Group 13 Elements 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 Group 13 Compounds as Lewis Acids Hydroboration Group 13-Based Reducing Agents From Borazine to Gallium Arsenide: 13–15 Compounds Low-Oxidation-State Compounds The Boryl Anion Indium-Mediated Allylations Thallium Reagents Summary Further Reading 4. Group 14 Elements 4.1 4.2 4.3 Silyl Protecting Groups A Case Study: Peterson Olefination Silanes 32 33 35 37 38 38 40 41 45 46 47 48 50 51 52 53 56 58 61 63 64 65 66 67 70 73 76 80 87 88 89 94 94 96 98 103 104 CONTENTS 4.4 4.5 4.6 4.7 4.8∗ 4.9∗ 4.10 4.11 4.12 The 𝛽-Silicon Effect: Allylsilanes Silyl Anions Organostannanes Polystannanes Carbene and Alkene Analogs Alkyne Analogs Silyl Cations Glycol Cleavage by Lead Tetraacetate Summary Further Reading 5A. Nitrogen 5A.1 Ammonia and Some Other Common Nitrogen Nucleophiles 5A.2 Some Common Nitrogen Electrophiles: Oxides, Oxoacids, and Oxoanions 5A.3 N–N Bonded Molecules: Synthesis of Hydrazine 5A.4 Multiple Bond Formation: Synthesis of Sodium Azide 5A.5 Thermal Decomposition of NH4 NO2 and NH4 NO3 5A.6 Diazonium Salts 5A.7 Azo Compounds and Diazene 5A.8∗ Imines and Related Functional Groups: The Wolff–Kishner Reduction and the Shapiro Reaction 5A.9 Diazo Compounds 5A.10 Nitrenes and Nitrenoids: The Curtius Rearrangement 5A.11 Nitric Oxide and Nitrogen Dioxide 5A.12 Summary Further Reading 5B. The Heavier Pnictogens 5B.1 Oxides 5B.2 Halides and Oxohalides 5B.3 Phosphorus in Biology: Why Nature Chose Phosphate 5B.4 Arsenic-Based DNA 5B.5 Arsenic Toxicity and Biomethylation 5B.6 Alkali-Induced Disproportionation of Phosphorus 5B.7 Disproportionation of Hypophosphorous Acid 5B.8 The Arbuzov Reaction 5B.9 The Wittig and Related Reactions: Phosphorus Ylides 5B.10 Phosphazenes 5B.11∗ The Corey–Winter Olefination 5B.12 Triphenylphosphine-Mediated Halogenations vii 106 109 112 113 115 120 122 124 127 128 129 130 131 133 135 137 138 140 144 146 149 151 155 155 156 158 160 163 166 168 171 173 175 176 180 185 187 viii CONTENTS 5B.13∗ The Mitsunobu Reaction 5B.14∗ The Vilsmeier–Haack Reaction 5B.15 SbF5 and Superacids 5B.16 Bismuth in Organic Synthesis: Green Chemistry 5B.17 Summary Further Reading 6. Group 16 Elements: The Chalcogens 6.1 The Divalent State: Focus on Sulfur 6.2 The Divalent State: Hydrogen Peroxide 6.3 S2 Cl2 and SCl2 6.4 Nucleophilic Breakdown of Cyclopolysulfur Rings 6.5 Cyclooctachalcogen Ring Formation 6.6 Higher-Valent States: Oxides and Oxoacids 6.7 Sulfur Oxochlorides 6.8 Ozone 6.9 Swern and Related Oxidations 6.10 Sulfur Ylides and Sulfur-Stabilized Carbanions 6.11∗ Hydrolysis of S2 F2 : A Mechanistic Puzzle 6.12 Higher-Valent Sulfur Fluorides 6.13 Martin Sulfurane 6.14 Lawesson’s Reagent 6.15 Sulfur Nitrides 6.16∗ Selenium-Mediated Oxidations 6.17 Higher-Valent Tellurium: A Mechanistic Puzzle 6.18 Summary Further Reading 7. The Halogens 7.1 7.2 7.3 7.4 7.5 7.6 7.7 7.8 7.9∗ 7.10 7.11 7.12 Some Notes on Elemental Halogens Alkali-Induced Disproportionation of Molecular Halogens Acid-Induced Comproportionation of Halate and Halide Hypofluorous Acid, HOF Electrophilic Fluorinating Agents: N-Fluoro Compounds Oxoacids and Oxoanions Heptavalent Chlorine Interhalogen Compounds Halogens in Organic Synthesis: Some Classical Reactions An Introduction to Higher-Valent Organoiodine Compounds 𝜆3 -Iodanes 𝜆5 -Iodanes: IBX and Dess–Martin Periodinane 188 191 193 195 200 200 202 204 205 209 211 213 215 219 222 226 228 231 234 236 238 240 243 247 250 251 252 254 258 260 261 264 268 271 275 276 283 284 288 CONTENTS 7.13 Periodic Acid Oxidations 7.14 Bromine Trifluoride 7.15∗ Aryl-𝜆3 -Bromanes 7.16 Summary Further Reading 8. The Noble Gases 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 8.9 8.10 8.11 8.12 8.13 The Xenon Fluorides: Fluoride Donors and Acceptors O/F Ligand Exchanges Xenon Fluorides as F+ Donors and Oxidants Hydrolysis of XeF2 and XeF4 Xenate and Perxenate Disproportionation of Xenate Hydrolysis of XeF4 Other Compounds Containing Xe–O Bonds Xe–N Bonds Xe–C Bonds Krypton Difluoride Plus Ultra Summary Further Reading ix 290 291 294 298 299 300 302 303 304 306 307 308 310 311 312 313 314 316 316 316 Epilogue 318 Appendix A. Inorganic Chemistry Textbooks, with a Descriptive-Inorganic Focus A.1 Introductory Texts A.2 Advanced Texts 319 319 319 Appendix B. A Short List of Advanced Organic Chemistry Textbooks 320 Index 321 Foreword Many years ago George Hammond and I taught a course at Caltech that included discussions of main-group chemistry. We tried to use inorganic textbooks that dealt with the subject, but we were not happy with them, as they paid no attention to reaction mechanisms. Discussions of nucleophilic and electrophilic reagents, associative and dissociative substitutions, reaction energy landscapes, and so on, were nowhere to be found. Faced with this problem, we decided to base our course on reaction mechanisms, but very few instructors adopted this approach in teaching main-group chemistry. Now, at long last, we have a book on main-group chemistry that students can learn from! They may even read it from cover to cover without going to sleep! The authors, Abhik Ghosh and Steffen Berg, have clearly demonstrated how a mechanistic approach makes the reactions of main-group elements interesting and understandable: Arrow pushing is the key! There are many parts of the book that I like very much. The treatment of the reactions of nitrogen compounds, largely neglected in inorganic courses, is particularly good. And one of my favorites, the very rich chemistry of high-valent halogen and xenon molecules, is excellent. The bottom line is that arrow pushing is a method that should be used to teach main-group chemistry. As the authors note, their book logically can be used to supplement standard inorganic texts. I urge instructors to try the Ghosh–Berg method when faced with teaching the dreaded “descriptive” section of the inorganic course. Arrow pushing not only is great fun, students who try it may actually learn main-group chemistry! Harry B. Gray California Institute of Technology February 2014 xi Preface Inorganic chemistry at core consists of a vast array of molecules and chemical reactions. To master the subject, students need to think intelligently about this body of facts, a feat that is seldom accomplished in an introductory course. All too often, young students perceive the field as an amorphous body of information that has to be memorized. We have long been intrigued by the possibility of changing this state of affairs by means of a mechanistic approach, specifically organic-style arrow pushing. We found that such an approach works well for all main-group elements, that is, elements from the s and p blocks of the periodic table. In particular, we found that arrow pushing works well for hypervalent compounds, where the central atom has more than eight electrons in its valence shell in the Lewis structure. Over time, we came to appreciate that full implementation of a mechanistic approach had the potential to transform the teaching of a substantial part of the undergraduate inorganic curriculum. This book is a realization of that vision. Arrow Pushing in Inorganic Chemistry is designed as a companion to a standard inorganic text. In general, we have devoted one chapter to each group of the main-group elements. Each chapter in this book is designed to supplement the corresponding chapter in a regular inorganic text. A student using this book is expected to have taken general chemistry and a good, introductory course in organic chemistry at the university level. Key prerequisites include elementary structure and bonding theory, a good command of Lewis structures, VSEPR theory, elementary thermodynamics (as usually outlined in general chemistry), simple acid–base calculations, basic organic nomenclature, and a good but elementary understanding of organic mechanisms. Because a basic knowledge of organic chemistry has been assumed, the general level of this book is somewhat higher than that of an undergraduate organic text. The material included in this book (along with related content from a standard inorganic text) has been regularly taught at the University of Tromsø in about 30 h of class time, roughly half of which has been devoted to problem-solving by students. A small number of somewhat specialized topics and review problems have been marked with an asterisk, to indicate that they may be skipped on first reading. We usually take up a few of these at the end of our course and in conjunction with a second or more specialized course. xiii xiv PREFACE The approach. Many students are deeply impressed by the logic of organic chemistry. Mechanistic rationales are available for essentially every reaction in the undergraduate (and even graduate) organic curriculum and students learn to write reaction mechanisms right from the beginning of their courses. A survey of current texts shows that a mechanistic approach is universally adopted in introductory organic courses. The situation with inorganic chemistry could not be more different; not one major introductory text adopts a mechanistic approach in presenting descriptive main-group chemistry! In a telling exercise, we went through several textbooks that do an otherwise excellent job of presenting descriptive inorganic chemistry, without finding the words “nucleophile” and “electrophile.” Not surprisingly, these texts do not present a single instance of arrow pushing either. Arrow pushing above all provides a logical way of thinking about reactions, including those as complex as the following: P4 + 3 NaOH + 3 H2 O → 3 NaH2 PO2 + PH3 24 SCl2 + 64 NH3 → 4 S4 N4 + S8 + 48 NH4 Cl 2 HXeO4 − + 2 OH− → XeO6 4− + Xe + O2 + 2 H2 O These reactions represent important facets of the elements involved but are typically presented as no more than facts. (Why does boiling white phosphorus in alkali lead to hypophosphite and not phosphate?—Current texts make no attempt to address such questions.) Arrow pushing demystifies them and places them on a larger logical scaffolding. The transformative impact of this approach cannot be overstated. Almost to a person, students who have gone through our introductory course say that they cannot imagine how someone today could remain satisfied with a purely descriptive, nonmechanistic exposition of inorganic main-group chemistry. A mechanistic approach has done wonders for the overall tenor of our classroom—now very much a “flipped classroom,” where arrow pushing, instead of videos, have afforded the “flip.” Well-designed traditional lectures are still important to us and our students, but they now account for only 50% of total contact hours, with the rest devoted to various types of active learning. Some students solve mechanism problems on their own, others do so in groups, and still others solve them on the blackboard in front of the class. Importantly, such a classroom affords continual feedback from the students so we always have a good idea of their level of understanding and can assist accordingly. Potential concerns. Given the plethora of advantages of a mechanistic approach, it’s worth reflecting why it has never been adopted for introductory inorganic chemistry. A plausible reason is that, in contrast to common organic functional groups, simple p-block compounds such as hydrides, oxides, halides, and so forth, tend to be much more reactive and their vigorous and even violent reactions have been much less thoroughly studied. As good scientists, inorganic chemists may have felt a certain inhibition about emphasizing an approach that has little grounding in experimental fact. This is a legitimate objection, but hardly a dealbreaker, in our opinion, for the following reasons. Our ideas on main-group element reactivity are not taken out of the blue but are based on parallels with well-studied processes in organic and organoelement chemistry. Second, it no longer necessarily takes a prohibitive amount of resources to test a mechanistic proposal, at least in a preliminary way. Quantum chemical calculations, particularly based on density functional theory (DFT), very often provide an efficient and economical way of evaluating reaction mechanisms. Third, and perhaps most important, it’s vastly better to be able to PREFACE xv formulate a hypothesis on how a reaction might happen than to have no inkling whatsoever about the mechanism. Content and organization. Chapter 1 attempts to provide a summary of all relevant introductory concepts, paving the way for a full appreciation of the rest of the book. The chapter begins with a discussion of nucleophiles and electrophiles, continues on to present a survey of the major organic reaction types (substitution, elimination, addition, etc.) and of some specifically inorganic reaction types (oxidative addition, reductive elimination, metathesis, migrations, etc.), and concludes with an elementary discussion of hypervalent compounds. The subsequent chapters are organized according to the groups of the periodic table, from left to right. Chapter 2 deals with the s-block elements, providing a combined treatment of hydrogen, the alkali metals, and the alkaline earth metals. For the p block, the chapter number is generally the same as the old group number; thus, the chalcogens are discussed in Chapter 6, the halogens in Chapter 7, and so on. The only exception is group 15, which we have split up into two chapters, 5a and 5b: Chapter 5a is devoted to nitrogen and Chapter 5b to the heavier pnictogens. As far as any given chapter is concerned, the goal has been not so much to provide a systematic account of a given group of main-group elements (although we believe that we have done so moderately well) as to help students figure out the inner workings of relatively complicated-looking reactions. We have done so by organizing each chapter as a series of vignettes, focusing on reactions that in our opinion are most conducive to sharpening students’ arrow-pushing skills. In-chapter review problems are designed to further hone these skills as well as to provide material for in-class discussions and recitation sections. We have refrained from including end-of-chapter problems, in part out of a desire to limit the book to a manageable length. Students in need of additional exercises should find an ample supply of reactions in their regular descriptive inorganic text. As far as our choice of reactions and topics is concerned, we have attempted to offer a stimulating mix of the traditional and the topical. For the traditional material, we have borrowed freely from introductory and advanced texts with a “descriptive inorganic” emphasis. These books are listed in Appendix 1. The Wikipedia has also been a valuable resource for this purpose. On occasion, we have played science historian and thrown in an anecdote or an amusing quote. The more cutting-edge material has been sourced from the research literature. Examples of such topics include: • • • • • • • Jones’s Mg(I)–Mg(I) reagent indium-mediated allylations heavy-element carbene, alkene, and alkyne analogs the Ruppert–Prakash and Togni reagents BrF3 and higher valent bromine compounds as synthetic reagents the recent arsenic-DNA controversy the possible role of borate minerals in the origin of life (possibly even on Mars!) Because this is an introductory text, however, we have cited the original research literature sparingly, often settling for a short list of suggested readings at the end of each chapter. Stylistic aspects. A few comments on stylistic aspects of the book might be helpful. Perhaps foremost among them is the use of color in our reaction mechanisms, which include blue, black, red, and green. In general, the first nucleophile in a given mechanism is always indicated in blue and the first electrophile in black. Later in the mechanism, if the atoms originating in the initial nucleophile take on a different role, such as that of an electrophile, xvi PREFACE they are still indicated in blue. Thus, for any given atom or group, its color is maintained the same throughout the mechanism so that its fate can be easily followed throughout the reaction pathway. Curly arrows have throughout been indicated in red; certain atoms “deserving” special attention are also indicated in red. In some cases, where a third reactant is involved, it is indicated in green. In general, the color of a newly formed bond is the same as the color of the lone pair or other electrons from which it may be thought to have originated for bookkeeping purposes. In this book, curly arrows typically begin from the nucleophilic electron pair and end on the electrophilic atom being attacked. In general, to prevent clutter, we have not shown lone pairs unless they are specifically engaged in a nucleophilic attack. We have made sparse use of multiple bonds involving higher valent p-block elements. Thus, we have preferred to use the left-hand structures for POCl3 and SO2 Cl2 , as opposed to the multiply bonded structures to the right: O P − Cl Cl Cl O − O S O + P Cl − Cl Cl O 2+ Cl Cl S O Cl Cl Despite the unrealistic formal charges, we believe that the structures on the left give a clearer sense of the bonding, whereas the multiple bonds shown to the right are harder to appreciate. It is not easy to explain to an undergraduate audience which specific orbitals constitute the double bonds in the right-hand structures. To instructors who would prefer to stick to the more conventional multiply bonded structures, we say: by all means do so; for the vast majority of reactions, arrow pushing will work equally well for both types of structures. The end of descriptive inorganic chemistry? An interesting question to consider is the following: Does a mechanistic approach, making extensive use of arrow pushing, signal of the end of descriptive inorganic chemistry? The answer, in our opinion, is both yes and no. By emphasizing arrow pushing as a universal tool for rationalizing main-group reactivity, we have placed the field at exactly the same level as organic chemistry. Just as no one speaks of “descriptive organic chemistry,” there is no point in treating main-group chemistry as a descriptive subject. That, of course, does not diminish the importance of facts and having an appropriate respect for them. Facts come first, whether it’s organic or inorganic chemistry, and mechanisms are primarily useful for understanding and rationalizing them. In that sense, mechanisms can never supplant a descriptive exposition of chemical facts. Abhik Ghosh and Steffen Berg The Arctic University of Norway, Tromsø, Norway Acknowledgments We are indebted to many friends and colleagues who generously assisted us in the preparation of this book. Prof. Carl Wamser of Portland State University and Dr. David Ware of The University of Auckland read and critiqued the entire manuscript. Our debt to these two loyal friends is immense. Others who read individual chapters and shorter sections include Paul Deck of Virginia Tech (halogens), Penny Brothers of The University of Auckland (Group 13 elements), Barry Rosen of Florida International University (Group 15 elements), Ged Parkin of Columbia University (higher-valent and hypervalent compounds), and Kyle Lancaster of Cornell University (the noble gases). We thank Steven Benner (FFAME, Gainesville, FL; arsenic-DNA), Tristram Chivers (University of Calgary; sulfur nitrides), Harry Gray (Caltech; higher-valent bromine reagents), Roald Hoffmann (Cornell; aspects of halogens), Pekka Pyykkö (University of Helsinki; inert pair effect), and Shlomo Rozen (Tel Aviv University; BrF3 ) for helpful advice and correspondence on the topics indicated within parentheses. Our long-time friend and collaborator Prof. Jeanet Conradie of the University of the Free State, South Africa, assisted us with the DFT calculations we needed for a better understanding of certain reactions. Carl Wamser and Penny Brothers also provided wonderful refuges—Portland, Oregon, and Auckland, New Zealand—where one of us (AG) could escape to and write. The Foreword has been written by Harry Gray, who seemed to us to be uniquely qualified for the purpose. In the 1960s, he and George Hammond tried to adopt a mechanistic approach in teaching aspects of main-group chemistry (see, e.g., Chemical Dynamics by J. B. Dence, H. B. Gray, and G. S. Hammond, Benjamin: 1968). Harry’s full-throated support of our own approach means a great deal to us. It is a pleasure to acknowledge Wiley editor Anita Lekhwani for her encouragement and wise counsel throughout the writing process. We are similarly grateful to Sangeetha Parthasarathy of Laserwords Pvt. Ltd. Chennai, India, for the considerable efforts involved in the final production of the book. Finally, we thank our families and some of our closest friends for their love and encouragement: AG thanks Avroneel, Sheila, Ranjita, Matthew, and Daniel; and SB thanks Kenneth, Andreas, Eirik, Tor Håvard, and above all Cathrine. xvii Advance praise for Arrow Pushing in Inorganic Chemistry: A Logical Approach to the Chemistry of the Main-Group Elements I tell my organic students to “think like a molecule”. What are the molecules doing, and why are they doing that? Since the essence of a chemical reaction is the reorganization of bonds (i.e., electrons), the primary tool for understanding it is arrow pushing. It’s a real delight to see that this fundamental approach indeed works beautifully in inorganic chemistry as well. It makes one wonder why it hadn’t been “discovered” sooner. Congratulations to the authors for an excellent expository textbook.— Professor Carl C. Wamser, Portland State University It’s great to see a key organic skill, arrow pushing, applied to inorganic chemistry, where there’s plenty extra to think about—redox chemistry along with wide variations in atomic size and electronegativity. The strength of the approach is that all this can be taken into account. A powerful new way of thinking for inorganic chemists!—Dr. David Ware and Professor Penny Brothers, University of Auckland, New Zealand In my Metals in Biology course, I tell my students the simplest lesson of chemistry: electrons flow from where they are to where they aren’t. This is the essence of the ‘arrow pushing’ formalism, which had its origins in physical organic chemistry. My early training in that field led me to use the arrow pushing language in my own research in bioinorganic chemistry. I am delighted to see this language applied much more generally to inorganic chemistry in this very illuminating and instructive book. Students will learn where electrons want to go and their appreciation of how reactions occur will be greatly enhanced. — Professor John T. Groves, Princeton University Nice up-to-date stuff, including frustrated Lewis pairs, Jones’s Mg(I) reagent, high-valent bromine and lots more! It would have been easy for the authors to ignore the last twenty years (or fifty) but they didn’t do that! — Professor Paul A. Deck, Virginia Tech I was struck by the sheer amount of innovation, thought, and attention to detail that has gone into the making of this book. In cases where arrow pushing does not immediately indicate a unique mechanism, the authors have even resorted to DFT calculations to resolve the ambiguity. — Professor Jeanet Conradie, University of the Free State, Republic of South Africa … Valence is an important concept in inorganic chemistry and it’s nice to see the authors do full justice to the topic. They carefully distinguish valence and oxidation state, which are often confused, and draw structures with appropriate formal charges that shed light on the bonding. Furthermore, their treatment of the fascinating chemistry of the higher-valent states of p-block elements is superb. — Professor Gerard Parkin, Columbia University … The marriage between descriptive inorganic chemistry and the language of organic reaction mechanisms is convincingly consummated in this new and most useful contribution. — Professor Peter R. Taylor, University of Melbourne 1 A Collection of Basic Concepts In solving a problem of this sort, the grand thing is to be able to reason backward. That is a very useful accomplishment, and a very easy one, but people do not practise it much. In the everyday affairs of life it is more useful to reason forward, and so the other comes to be neglected. Sherlock Holmes in A Study in Scarlet, By Sir Arthur Conan Doyle We assume you’ve had an introductory course in organic chemistry and hope you found it logical and enjoyable. The logic of organic chemistry is of course key to its charm, and mechanisms are a big part of that logic. In this book, we will present a similar approach for inorganic chemistry, focusing on the main-group elements, that is, the s and p blocks of the periodic table (Figure 1.1). As in organic chemistry, our main tool will be the curly arrows that indicate the movement of electrons, typically electron pairs, but on occasion also unpaired electrons. As we shall see, this approach—arrow pushing—works well in inorganic chemistry, especially for the main-group elements. We want to get you started with arrow pushing in an inorganic context as quickly as possible, but we’d also like to make sure that you are equipped with the necessary conceptual tools. In this chapter, we’ll try to provide you with that background as efficiently as possible. Unavoidably, the concepts form a somewhat disparate bunch but they do follow a certain logic. Sections 1.1–1.6 introduce the idea of nucleophiles and electrophiles, in the context of the SN 2 displacement, and discuss physical concepts such as electronegativity, polarizability, pKa , redox potentials, and bond energies in relation to chemical reactivity. Armed with these concepts, we’ll devote the next several Sections 1.7–1.21 to survey key mechanistic paradigms, focusing on major organic reaction types but also on a few special inorganic ones. Sections 1.22 and 1.23 then present practical tips on arrow pushing, that Arrow Pushing in Inorganic Chemistry: A Logical Approach to the Chemistry of the Main-Group Elements, First Edition. Abhik Ghosh and Steffen Berg. © 2014 John Wiley & Sons, Inc. Published 2014 by John Wiley & Sons, Inc. 1 2 A COLLECTION OF BASIC CONCEPTS d-Block p-Block s-Block 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 He H Li Be B C N O F Ne Na Mg Al Si P S Cl Ar K Ca Sc Ti V Cr Mn Fe Co Ni Cu Zn Ga Ge As Se Br Kr Rb Sr Y Zr Nb Mo Tc Ru Rh Pd Ag Cd In Sn Sb Te I Xe Cs Ba Lu Hf Ta W Re Os Ir Pt Au Hg Tl Pb Bi Po At Rn Fr Ra Lr Rf Db Sg Bh Hs Mt Ds Rg Cn Figure 1.1 The periodic table: group numbers and the s, p, and d blocks. is, how you might approach a given mechanistic problem. In the course of our mechanistic survey, we’ll encounter a number of so-called hypervalent p-block compounds, which you may not have encountered until now. These call for a brief discussion of the bonding involved, which we will present in Sections 1.24–1.27. That said, we will not cover some of the more elementary aspects of structure and bonding theory, including the very useful VSEPR (valence shell electron pair repulsion) model; feel free to go back to your general or organic chemistry text for a quick refresher. 1.1 NUCLEOPHILES AND ELECTROPHILES: THE SN 2 PARADIGM In this book, we will be overwhelmingly concerned with polar or ionic mechanisms. These involve the movement of electron pairs, unlike radical reactions which involve unpaired electrons. The components of a polar mechanism can generally be classified as nucleophiles or electrophiles. A nucleophile (“nucleus-lover”) is typically an anion or a neutral molecule that uses an electron pair to attack another atom, ion, or molecule. The species being attacked is called an electrophile (“electron-lover”). The terms “nucleophile” and “electrophile” often refer to the classic SN 2 reaction of organic chemistry. In the example below (which happens to be a Williamson ether synthesis), the methoxide anion is the nucleophile, methyl iodide is the electrophile, and iodide is the leaving group. H C H H − O H C H H I H H H H C C O H H + I − (1.1) A key feature of the SN 2 reaction is that the nucleophile attacks from the “back side” relative to the leaving group, leading to an umbrella-like inversion of the carbon undergoing 1.1 NUCLEOPHILES AND ELECTROPHILES: THE SN 2 PARADIGM − H, − BH4 , RLi , RMgBr , RC R3N , − AIH4 − CN , − HO , − RS , − Br , R3P, − ROH, RO , RSH , RSR′, − − F , Cl , Figure 1.2 − − C , HC − N + N 3 CO2Et CO2Et NR − HOO − S C − I N S C − N Some common nucleophiles, with the nucleophilic atoms indicated in blue. substitution. If this carbon atom is stereogenic,1 such an inversion of configuration may be discerned experimentally, as in the example below; otherwise the inversion is not detectable, even though it occurs. − Br − RS Br − (1.2) RS H Me Me H Several common nucleophiles are depicted in Figure 1.2, where R and R′ denote alkyl groups. Many of them are nitrogen-based, such as ammonia, amines (RNH2 ), and azide (N3 − ), or oxygen-based, such as water, alcohols (ROH), and alkoxide (RO− ) and carboxylate (RCO2 − ) anions. Sulfur-based nucleophiles such as thiols (RSH), thiolates (RS− ), and thioethers (RSR′ ) are also widely used in chemical synthesis. Triphenylphosphine, a phosphorus nucleophile, is an important reagent in organic synthesis, as well as an important transition-metal ligand. Halide ions are widely employed as both nucleophiles and leaving groups. Hydride is used both as a base (typically as NaH or KH) and as a nucleophile (often in complexed forms such as BH4 − or AlH4 − ). Carbon nucleophiles play a central role in organic chemistry, as they form the basis of carbon–carbon bond formation. A few are shown in Figure 1.2, including such carbanionic species as organolithiums (RLi), Grignard reagents (typically written as RMgBr), and the cyanide (CN− ) and acetylide (R–C≡C− ) anions. Other examples such as enolates, enols, and enamines will be briefly discussed in Section 1.15. Some common electrophiles are shown in Figure 1.3. These include protons and positively charged metal ions, electron-deficient species such as trivalent group 13 compounds (e.g., BF3 , AlCl3 ), the cationic carbon in carbocations, the halogen-bearing carbon in alkyl 1A stereogenic center is an atom in a molecule for which interchanging any two of its substituents leads to a different stereoisomer. The term was introduced by Mislow and Siegel in an important foundational paper on modern stereochemical concepts and terminology: Mislow, K.; Siegel, J. J. Am. Chem. Soc. 1984, 106, 3319–3328. 4 A COLLECTION OF BASIC CONCEPTS Figure 1.3 green. 2+ Mg , + H, + H3O , + Li , BF3 , AlCl3 , TlCl3 , RX, + R , + RCO, R3SiX, PCl5 , Ph3BiCl2, SF4 , SO3 , SeCl2 , SeO2 , X2 , BrF3, XeF2 R3SnX, Pb(OAc)4, Some common electrophiles; X is a halogen. The electrophilic atoms are indicated in halides, the Si atom in silyl halides, molecular halogens, and even the fluorine atoms in xenon difluoride (XeF2 ). The ease with which a given SN 2 displacement occurs depends on multiple factors, such as the nucleophilicity of the incoming nucleophile (which depends on both its electronic and steric character), steric hindrance at the electrophilic carbon center, the effectiveness of the leaving group, and the solvent and other environmental effects. By defining a standard substrate and standard reaction conditions, the reactivity of different nucleophiles may be quantified. One such measure of nucleophilicity is the Swain–Scott nucleophilicity constant n, for which methyl iodide is chosen as the standard substrate and reaction rates are measured in methanol at 25 ∘ C: nCH3 I = log kNu kCH3 OH where kNu is the rate constant for the nucleophile of interest (Nu) and kCH3 OH is the rate constant for methanol itself as the nucleophile. Table 1.1 lists nCH3 I values for a number of representative nucleophiles, along with the pKa values of their conjugate acids (i.e., a measure of the basicity of the nucleophiles). Observe that there is only a very rough correlation between nCH3 I and the conjugate acid pKa ; we’ll return to this point in the next section. Table 1.2 presents a more qualitative characterization of some common nucleophiles, classifying them from strong to very weak. Table 1.1 shows that, for a given electrophile (CH3 I) and standard conditions, the rate constants for common nucleophiles vary by a factor of well over a billion (109 ). This tremendous variation of reactivity of the different nucleophiles might pose a conundrum in relation to their synthetic utility. Note (from either Table 1.1 or 1.2) that alkoxide (RO− ) anions are some 103 –104 times more nucleophilic than neutral alcohols, and the rates for carboxylate anions (RCO2 − ), relative to the un-ionized carboxylic acids, differ by even more: 105 –106 . With such low rates, are alcohols and carboxylic acids, in their un-ionized forms, at all useful as nucleophiles? The answer is a clear yes. In acidic media, many of the anionic nucleophiles simply don’t exist; they are entirely protonated. Under such conditions, weak nucleophiles such as alcohols and carboxylic acids react effectively with cationic electrophiles such as carbocations. Second, although weaker nucleophiles may not react at a useful rate with alkyl halides, many of them do react at perfectly acceptable rates 1.2 WHAT MAKES FOR A GOOD NUCLEOPHILE? 5 TABLE 1.1 Swain–Scott Nucleophilicity Constants and Conjugate Acid pKa Values of Some Common Nucleophiles Nucleophile nCH Conjugate Acid pKa CH3 OH NO3 – F– CH3 CO2 – Cl – R2 S NH3 N3 − C6 H5 O – Br – CH3 O – HO – NH2 OH NH2 NH2 (CH3 CH2 )3 N CN– I– HO2 – (CH3 CH2 )3 P C6 H5 S – C6 H5 Se− 0.0 1.5 2.7 4.3 4.4 5.3 5.5 5.8 5.8 5.8 6.3 6.5 6.6 6.6 6.7 6.7 7.4 7.8 8.7 9.9 10.7 −1.7 −1.3 3.45 4.8 −5.7 −6 to −7 9.25 4.74 9.89 −7.7 15.7 15.7 5.8 7.9 10.7 9.3 −10.7 11.75 8.7 6.5 5.9 3I TABLE 1.2 Qualitative Classification of Nucleophiles, Based on the Swain–Scott Nucleophilicity Constants nCH I 3 Nucleophiles RS− , HS− , I− N3 − , CN− , RO− , OH− , Br− NH3 , RCO2 − , F− , Cl− ROH, H2 O RCO2 H Relative Rate Characterization >105 Strong Good Moderate Weak Very weak 104 103 1 10−2 with stronger electrophiles such as BF3 or neutral organosilicon compounds in general. The usefulness of a given nucleophile thus depends enormously on the reaction conditions. 1.2 WHAT MAKES FOR A GOOD NUCLEOPHILE? Nucleophilicity and electrophilicity are closely related to Lewis basicity and acidity, respectively. Nucleophiles are Lewis bases (electron-pair donors) and electrophiles are Lewis acids (electron-pair acceptors). Now, as discussed previously, nucleophilicity is measured in terms of the rate of a nucleophilic attack, so it’s a kinetic concept. Basicity, on the other hand, is measured in terms of the equilibrium constant for protonation (or for association with some Lewis acid), so it is a thermodynamic concept. Another difference is that, 6 A COLLECTION OF BASIC CONCEPTS whereas Brønsted basicity refers to the thermodynamic affinity for protons, nucleophilicity in organic chemistry typically refers to the rate of attack on a carbon center. Moreover, in this book, we will talk about nucleophilic attacks on pretty much any p-block element! Understandably, therefore, you should not expect more than a rough correlation between the nucleophilicity of a nucleophile and its basicity. To better appreciate this point, let us go back to Table 1.1, which lists a number of nucleophiles in increasing order of nCH3 I , an arbitrarily defined measure of nucleophilicity. Observe that the basicities of the nucleophiles, as indicated by the pKa values of their conjugated acids, increase in a general but highly erratic way with the value of nCH3 I . To illustrate, whereas tertiary phosphines are more nucleophilic than tertiary amines by about two orders of magnitude, the former are less basic than the latter by roughly the same factor. What factors then make for a good nucleophile? The following trends have been observed: • Anions are better nucleophiles than the related neutral molecules. Thus: RO – > ROH; RS – > R2 S; NH2 – > NH3 where R = H, alkyl, or aryl. • For analogous species in a given period, nucleophilicity decreases as one progresses to the right of the periodic table: NH3 > H2 O; R3 P > R2 S The more electronegative elements hold on to their electrons more tightly. • Nucleophilicity increases as one goes down a given group of the periodic table. Thus, for example PR3 > NR3 ; PhSe – > PhS – > PhO – The larger atoms are less electronegative and the anions derived from them are more polarizable, which translates to increasing nucleophilicity as one goes down a group. Given that electronegativity and size (atomic radius) are the two key determinants of nucleophilicity, it’s useful to remind ourselves how the two atomic properties vary across the periodic table. Figure 1.4 presents Pauling electronegativities and Figure 1.5 the atomic radii of the s- and p-block elements. Note that electronegativity increases from left to right along a given period, and decreases down a group. Atomic radii shrink from left to right in a given period and increase down a group. Against this backdrop, the relative nucleophilicities of the halide anions make for somewhat of a puzzle. The Swain–Scott nucleophilicities (Tables 1.1 and 1.2), based on methanol as solvent, are in the order: I – > Br – > Cl – > F – The same order is found in other protic solvents. This is also the order expected on the basis of polarizability: the larger and more polarizable anions should be the most nucleophilic. In polar aprotic solvents (e.g., DMSO, DMF, THF, etc.), however, the relative rates are completely reversed: F – ≫ Cl – > Br – > I – 1.2 WHAT MAKES FOR A GOOD NUCLEOPHILE? H 2.20 7 He Li 0.98 Be 1.57 B 2.04 C 2.55 N 3.04 O 3.44 F 3.98 Ne Na 0.93 Mg 1.31 Al 1.61 Si 1.90 P 2.19 S 2.58 Cl 3.16 Ar K 0.82 Ca 1.00 Sc Ti Rb 0.82 Sr 0.95 Y Zr Nb Mo Tc Cs 0.79 Ba 0.89 – Hf Ta Re Os Fr 0.7 Ra 0.9 V Cr W Co Ni Cu Zn Ga 1.81 Ge 2.01 As 2.18 Se 2.55 Br 2.96 Kr 3.00 Ru Rh Pd Ag Cd In 1.78 Sn 1.96 Sb 2.05 Te 2.1 I 2.66 Xe 2.60 Pt Au Hg Tl 1.62 Pb 2.33 Bi 2.02 Po 2.0 At 2.2 Rn 2.2 Mn Fe Ir Figure 1.4 Pauling electronegativities of the main-group elements. A relatively self-explanatory color code has been employed to give a semiquantitative visual indication of the electronegativities. Ne H 31 53 Li Be B C N O F Ne 167 112 87 67 56 48 42 38 Na Mg Al Si P S Cl Ar 190 145 118 111 98 88 79 71 K ca Ga Ge As Se Br Kr Sc Ti V Cr Mn Fe Co Ni Cu Zn 243 194 136 125 114 103 94 88 Rb Sr In Sn Sb Te I Xe 265 219 156 145 133 123 115 108 Cs Ba Tl Pb Bi Po At Rn 156 154 143 135 Y – 298 253 Zr Nb Mo Tc Ru Rh Pd Ag Cd Hf Ta W Re Os Ir Pt Au Hg 120 Figure 1.5 Atomic radii (pm) of s- and p-block elements. (Clementi, E.; Raimond, D. L.; Reinhardt, W. P. J. Chem. Phys. 1967, 47, 1300–1307.) This remarkable reversal is due to hydrogen bonding, or the lack thereof in aprotic solvents. As a powerful hydrogen-bond acceptor, fluoride is understandably a poor nucleophile in protic solvents. Iodide, as the worst hydrogen-bond acceptor, is thus a much more active nucleophile in protic solvents. In the absence of hydrogen-bonding interactions with the solvent, which is the case in dry polar aprotic solvents, fluoride is the strongest nucleophile. 8 A COLLECTION OF BASIC CONCEPTS To a significant extent, the high nucleophilicity of “naked” fluoride ions may be attributed to the strength of the C–F bond (more on which in Section 1.6). Because the SN 2 transition state involves bond formation between the incoming nucleophile and carbon, the strength of that bond is a key determinant of nucleophilicity. Last but not least, steric effects are yet another key determinant of nucleophilicity. We will discuss steric effects to some extent in Section 1.7. 1.3 HARD AND SOFT ACIDS AND BASES: THE HSAB PRINCIPLE Several of the factors affecting nucleophilicity may be nicely rolled together into the concept of hard and soft Lewis acids and bases—HSAB, for short. The HSAB concept was introduced by Ralph Pearson over 50 years ago and was subsequently put on a firmer theoretical foundation by Pearson and Parr, among others. Hard acids and bases are relatively unpolarizable and have relatively high surface charge density, positive or negative; soft acids and bases are relatively polarizable and have low surface charge density, positive or negative. Of course, there are many borderline cases. High surface charge density (hardness) typically results from a high formal charge (FC), positive or negative, and small atomic/ionic size, and the opposite is true for low surface charge density (softness). Examples of hard, borderline, and soft acids and bases are shown in Table 1.3. The utility of the hardness/softness concept derives from the HSAB principle, which states that soft bases react faster and form stronger bonds with soft acids, and hard bases react faster and form stronger bonds with hard acids. A vast amount of chemistry can be rationalized with this principle. The HSAB concept greatly facilitates our appreciation of nucleophilicity: softer bases often make better nucleophiles. Phosphines, for example, are typically better nucleophiles than the analogous, harder amines, and sulfur compounds are better nucleophiles than their oxygen analogs. In this book, some of the best illustrations of the HSAB principle will be provided by the so-called ligand exchange or metathesis reactions, which are discussed in more detail in Section 1.19. The principle helps us in deciding whether a metathesis reaction will proceed in a given direction or not: AB + CD → AC + BD (1.3) TABLE 1.3 Qualitative Listing of Hard, Intermediate, and Soft Acids and Basesa Acids Bases Hard H+ , H–X, Li+ , Na+ , R3 SiX Mg2+ , Ca2+ , AlX3 , SnCl4 , TiCl4 NH3 , RNH2 H2 O, HO− , ROH, RO− , RCO2 − Cl− , F− , NO3 − Intermediate CuX2 , ZnX2 , SnX2 , GaX3 , R3 C+ , R3 B Br− , NNN− (azide), ArNH2 pyridine Soft RCH2 X, RSX, RSeX, I2 , Br2 , BrF3 , CuX, Ag+ , Pd(X/R)2 , Pt(X/R)2 , Hg(X/R)2 , zero-valent metals RSH, RS− , R2 S, RSe− , I− , R3 P, NC− , CO, RCH=CHR, benzene a Where warranted, the atom of interest is indicated in bold. 1.4 pK a VALUES: WHAT MAKES FOR A GOOD LEAVING GROUP? 9 Let us take a couple of concrete examples. SeCl2 + 2 (CH3 )3 SiBr → SeBr2 + 2 (CH3 )3 SiCl (1.4) PCl3 + AsF3 → PF3 + AsCl3 (1.5) In reaction 1.4, Se is a softer Lewis acid than Si, and bromide is a softer Lewis base than chloride. It makes sense therefore that Se and Br should link up, as should Si and Cl. In the second example (reaction 1.5), As is a softer Lewis acid center than P, and chloride is a softer Lewis base than fluoride. These ligand exchanges are thus consistent with the HSAB principle. 1.4 pK a VALUES: WHAT MAKES FOR A GOOD LEAVING GROUP? Compared with the multitude of factors affecting nucleophilicity, the efficacy of a leaving group is much more easily predictable. In short, a weaker Brønsted base makes a better leaving group. We can simply look up the pKa of the conjugate acid of a leaving group to arrive at a good idea of its leaving ability. Table 1.4, a short pKa table, will serve our purposes very well. Observe that the best leaving groups are conjugate bases of the strongest acids. Thus, iodide and bromide are excellent and popular leaving groups in organic chemistry. The worst leaving groups are very strong bases, such as amide, hydride, and alkyl anions. Hydroxide and alkoxide (RO− ) are also poor leaving groups in organic chemistry. The Williamson ether synthesis mentioned above (reaction 1.1) illustrates this last point well. Like all elementary reactions, the reaction is in principle reversible, but the reverse reaction, I− displacing a CH3 O− anion, does not occur for all intents and purposes. A couple of additional observations are worth making, again with specific reference to organic chemistry. TABLE 1.4 Common Leaving Groups and the pKa Values of Their Conjugate Acids Good Bad Leaving Group Conjugated Acid pKa I– Br – Cl – HSO4 − p-CH3 –C6 H4 –SO3 – H2 O F– CH3 COO – NH3 HO – CH3 O – NH2 – H– CH3 –CH2 –CH2 –CH2 – HI HBr HCl H2 SO4 p-CH3 –C6 H4 –SO3 H H3 O+ HF CH3 COOH NH4 + H2 O CH3 OH NH3 H2 CH3 –CH2 –CH2 –CH3 −10 −9 −8 −3 −3 −1.7 3.2 4.74 9.25 15.74 15.2 38 42 50 10 A COLLECTION OF BASIC CONCEPTS Fluoride and cyanide are very much worse leaving groups than the pKa values of HF and HCN would imply. This presumably reflects the great strength of the C–F and C–CN bonds. Sulfonates are better leaving groups than the pKa values of sulfonic acids suggest. Arenesulfonates (ArSO3 − ), especially p-toluenesulfonate (also known as tosylate, TsO− ), are popular leaving groups in organic chemistry because alkyl tosylates may be readily prepared from the corresponding alcohols. The trifluoromethanesulfonate anion (also known as triflate, TfO− ) leaves with even greater alacrity, and even better leaving sulfonate-based leaving groups have been developed: F − SO3 F − SO3 F Tosylate Triflate A fact that many students struggle with on their first introduction to organic chemistry is the following: the iodide ion is both an excellent nucleophile and an excellent leaving group; by contrast, alkoxide ions (RO− ) are good nucleophiles but lousy leaving groups. What accounts for the difference? The solution to this conundrum is that, although both nucleophiles and leaving groups are Lewis bases, very different factors control their efficacy. Iodide’s nucleophilicity is attributed primarily to its polarizability or softness. The nucleophilicity of alkoxide ions owes more to the hard–hard interaction between O− and C𝛿+ and the resulting strength of the C–O bond. On the other hand, there is a clear inverse correlation between the efficacy of leaving groups and their Brønsted basicity. Thus, iodide is an excellent leaving group because it is a very weak base. Alkoxide anions, being strong bases, are lousy leaving groups. Protonation greatly enhances the efficacy of leaving groups. For example, the bromide anion by itself (e.g., in the form of NaBr) does not react with an alcohol, OH− being a notoriously poor leaving group in organic chemistry. H H OH C H Br C − H C H H H H H + HO C − (1.6) Br H Protonation of the OH group by concentrated HBr, however, enables the departure of water, a far better leaving group, as shown below: H H H C H Br + O H H H C − HH C H H H H + C Br O H (1.7) 1.6 THERMODYNAMIC CONTROL: BOND DISSOCIATION ENERGIES (BDEs) 11 Concentrated HBr is therefore a suitable reagent for converting simple alcohols to the corresponding alkyl bromides (assuming there are no other acid-sensitive groups in the molecule). We’d be remiss if we didn’t make some amends for presenting a rather “organic-centered” view of leaving groups: a variety of other factors are at play when the electrophilic center is not carbon. Perhaps the most important of these is the fact that single bonds between electronegative elements are typically weak and are easily cleaved. Unlike in organic chemistry, a hydroxide anion is a fair leaving group for a substrate of the form ROOH. Similarly, although thiolates (RS− ) are hopelessly poor leaving groups in organic chemistry, rings of divalent sulfur atoms are readily broken down by nucleophiles, with S− leaving groups as intermediates (as discussed in Section 6.4). 1.5 REDOX POTENTIALS Broadly speaking, nucleophilicity correlates with reduction potential. Thus, stronger reducing agents tend to make better nucleophiles, which makes sense because both properties are related to electron donation. The correlation, however, is best limited to a set of structurally closely related nucleophiles. For a broader correlation, Edwards and Ritchie proposed an “oxibase” scale, which afforded a linear correlation of the reactivity of a nucleophile with the reduction potential of its oxidized form and the pKa of its conjugate acid. Although space doesn’t permit a more detailed discussion of this scale, redox potentials are broadly important for the subject matter of this book. Table 1.5 lists reduction potentials of representative inorganic substances of potential interest in this book. Observe that the half-reactions are all written as reductions, following current convention, as well as to avoid ambiguity. In this convention, the more positive the reduction potential, the more the reduction is favored thermodynamically. Strong oxidants thus exhibit high (i.e., more positive) reduction potentials. A couple of examples should illustrate the utility of this table. A table such as Table 1.5 provides an indication of whether an oxidant or reductant is suitable for a given redox role. Thus, with a high reduction potential (1.19 V in Table 1.5), ClO2 is clearly a strong oxidant, which underlies its wide use as a disinfectant. Observe that several of the reductions involve an oxidant (e.g., O2 , H2 O2 , NO3 − ) in acid solution. This makes sense because protonation is expected to make an oxidant even more powerful, that is, an even more avid acceptor of electrons. Not much more needs to be said about redox potentials at this point. We will refer back to Table 1.5 once in a while when we make arguments based on redox potentials. 1.6 THERMODYNAMIC CONTROL: BOND DISSOCIATION ENERGIES (BDEs) Many of the reactions discussed in this book occur under thermodynamic control. In other words, the activation energies for the various pathways are low enough and the temperature is high enough so that the products formed are thermodynamically the most stable ones possible. In contrast, under kinetic control, reaction rates determine the products observed and certain thermodynamically favored products may not predominate because their formation is too slow under the reaction conditions (particularly temperature). Reactions under 12 A COLLECTION OF BASIC CONCEPTS TABLE 1.5 Standard Reduction Potentials (E∘ , V) at 25 ∘ C, 1.0 M, 1 atm. E∘ (V) Half-Reaction F2 (g)+ 2e− → 2F− (aq) (aq) + 2H+ + 2e− +2.87 → Xe(g) + 2HF(aq) +2.32 O3 (g) + 2H+ (aq) + 2e− → O2 (g) + H2 O(aq) +2.07 XeF2 H2 O2 (aq) + 2H+ (aq) + 2e− → 2H2 O +1.78 PbO2 (s) + 4H+ (aq) + SO4 2− (aq) + 2e− → PbSO4 (s) + 2H2 O +1.70 HClO2 (aq) + 2H+ (aq) + 2e− → HOCl(aq) + H2 O +1.67 2HOCl(aq) + 2H+ + 2e− → Cl2 (g) + 2H2 O +1.63 Cl2 (g) + 2e− − → 2Cl (aq) +1.36 O2 (g) + 4H+ (aq) + 4e− → 2H2 O +1.23 Tl3+ (aq) + 2e− → Tl+ (aq) +1.23 ClO2 (g) + H+ (aq) + e− → HClO2 (aq) +1.19 Br2 (aq) + 2e− → 2Br− (aq) +1.09 NO3 − (aq) + 4H+ (aq) + 3e− → NO(g) + 2H2 O +0.96 O2 (g) + 2H+ (aq) + 2e− → H2 O2 (aq) +0.68 I2 (s) + 2e− → 2I− (aq) +0.54 O2 (g) + 2H2 O + 4e− → 4OH− (aq) SO2 (g) + 4H+ (aq) + 4e− → S(s) + 2H2 O SO4 2− (aq) + 4H+ + 2e− → SO2 (g) + 2H2 O 4+ (aq) + 2e− +0.40 +0.40 +0.20 2+ +0.13 𝟐H+ (aq) + 𝟐e− → H𝟐 (g) 0.00 Sn 2+ Sn (aq) + 2e− → Sn (aq) → Sn(s) −0.14 PbSO4 (s) + 2e− → Pb(s) + SO4 2− (aq) −0.31 2H2 O + 2e− → H2 (g) + 2OH− (aq) −0.83 3+ Al (aq) + 3e− → Al(s) Be2+ (aq) + 2e− → Be(s) −1.66 −1.85 Mg2+ (aq) + 2e− → Mg(s) −2.37 Na+ (aq) + e− → Na(s) −2.71 Ca2+ (aq) + 2e− → Ca(s) −2.87 K+ (aq) + e− → K(s) −2.93 Li + (aq) + e− → Li(s) −3.05 thermodynamic control often lead to the formation of an overall stronger set of bonds; a general idea of bond dissociation energies (BDEs) is therefore quite useful. Table 1.6 lists some typical single BDEs. A few examples of BDE considerations are as follows: Bonds between highly electronegative elements are weak and easily broken, for example, O–O, N–O, X–X, N–X, O–X, and so on, where X is a halogen. 1.6 THERMODYNAMIC CONTROL: BOND DISSOCIATION ENERGIES (BDEs) 13 TABLE 1.6 Typical Single Bond Dissociation Energies (kJ/mol, in black) and Bond Distances (pm, in green) for Selected p-Block Elements H C N O F H C N O F Si P S Cl Br I 436 74 414 110 389 98 464 94 569 92 323 145 318 138 339 123 431 127 368 142 297 161 347 154 293 147 351 143 439 141 289 184 264 187 259 181 330 176 276 191 238 210 159 140 201 136 272 134 187 209 180 174 201 169 243 184 203 138 132 184 130 368 183 351 176 170 205 165 180 201 199 159 128 540 181 490 174 285 168 255 163 197 178 197 176 234 213 227 226 221 360 216 289 231 250 213 220 230 214 331 209 272 224 213 243 213 208 251 203 213 218 237 243 200 218 213 209 232 192 228 180 247 Si P S Cl Br I 151 266 Carbon, silicon, and phosphorus form strong bonds with O and F. In addition, the C=O (∼899 kJ/mol) and P+ –O− (∼544 kJ/mol) BDEs are very high and these bonds tend to form easily under hydrolysis. These elements are thus said to be strongly oxophilic and fluorophilic. The HF bond is also extremely strong (BDE 569 kJ/mol), which in part explains why, unlike the other hydrohalic acids, HF is a weak acid. Thus, a number of p-block element fluorides react with proton sources to yield HF. The bond distances listed in Table 1.6 do not warrant much comment. By all means, browse them briefly; they are simply meant to give you a sense of the comparative dimensions of different bonds. Observe that there is no particular correlation between bond distances and BDEs. For bonds between a given pair of elements, however, a longer bond does correspond to a lower BDE. ♦♦♦ Our discussion until now has centered around the SN 2 displacement. With some of the key physical concepts in place, we are now in a good position to survey a number of other fundamental mechanisms. These are arranged in somewhat arbitrary order as follows: • The E2 mechanism (Section 1.7) • Proton transfers (PTs) (Section 1.8) 14 A COLLECTION OF BASIC CONCEPTS • • • • • • • • • • • • • Associative and dissociative processes (Section 1.9) SN 2-Si (Section 1.10) Two-step mechanisms: the SN 1 and E1 pathways (Section 1.11) Electrophilic addition to C–C multiple bonds (Section 1.12) Electrophilic substitution on aromatics: Addition–elimination (Section 1.13) Nucleophilic addition to C–heteroatom multiple bonds (Section 1.14) Carbanions and ylides (Section 1.15) Carbenes (Section 1.16) Oxidative addition and reductive elimination (Section 1.17) Migrations (Section 1.18) Ligand exchanges (Section 1.19) Radical reactions (Section 1.20) Pericyclic reactions (Section 1.21) ♦♦♦ 1.7 BIMOLECULAR 𝜷-ELIMINATION (E2) A process that often competes with SN 2 displacements for organic systems is E2 (which stands for “elimination, bimolecular”). When there is one or more hydrogens 𝛽 with respect to the leaving group (see reaction 1.8) and the incoming nucleophile is a strong enough base, bimolecular elimination occurs, often in competition with nucleophilic displacement, as shown below: Me Me Me C − O H H C β Me Me H − Br − C α Me Me C OH + H C (1.8) C Me Br Me Me H An important point is that, although an E2 reaction involves movement of three electron pairs, it all happens as a concerted one-step process. A sterically hindered carbon center, such as the tertiary carbon in a t-butyl halide, is generally not conducive to an SN 2 displacement. Me X Me Me t-Butyl halide 1.8 PROTON TRANSFERS (PTs) 15 An E2 elimination is often the favored pathway in such cases. Similarly, a strong, sterically hindered base also tends to favor an E2 over an SN 2 pathway. A good example is potassium t-butoxide, which is used in reaction 1.8. Examples of sterically hindered nitrogen bases include N,N-diisopropylethylamine (DIPEA, also known as Hünig’s base) and the much stronger lithium diisopropylamide (LDA). The pKa of the conjugate acid of DIPEA is about 9.0. Amidines, which are all-nitrogen analogs of carboxylic acids, tend to be significantly more basic than tertiary amines. Two moderately sterically hindered bicyclic amidines—1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5-diazabicyclo[4.3.0]non-5-ene (DBN)—are fairly widely used as bases promoting E2 eliminations. N N N N DBN DBU The pKa values of the conjugate acids of DBU and DBN have been estimated to be about 2–3 pKa units higher than those of tertiary amines such as triethylamine or DIPEA. We will conclude this section with a couple of interesting tidbits. The first is a piece of information: DBU is not only a synthetic base but also a natural product, an alkaloid isolated from the Caribbean (Cuban) marine sponge Niphates digitalis. The second is a question for you to consider. Observe that DBU and DBN have two nitrogens each. Which is the more basic nitrogen? Why? 1.8 PROTON TRANSFERS (PTs) PTs between electronegative atoms are fast and reversible. They are enormously important, not only in organic and inorganic chemistry but also in biology. In terms of arrow pushing, PTs look very much like SN 2 displacements: − Nu H H + Nu Nu Nu − (1.9) Sometimes the proton donor is obvious: in an aqueous solution it is typically the H3 O+ ion; under nonaqueous conditions it may be a strong acid such as H2 SO4 or HCl. In such cases, the proton donor may not be explicitly shown but be simply indicated as H+ : Nu − + H Nu H (1.10) Some important concrete examples of PTs are as follows: carbonyl and nitrile groups undergo protonation: 16 A COLLECTION OF BASIC CONCEPTS (a) + O R1 H O R1 H H H O + + O H H R2 R2 + O (b) H R C N R H H (1.11) + N C H + O H H The significance of these protonations is that the cations that result are much stronger electrophiles than the uncharged functional groups. In the same vein, alcohols and thiols may be deprotonated, as shown below, and the resulting anions are much stronger nucleophiles than their uncharged precursors: (a) (b) − H O R H R H − OR − EtOH + SR S − EtO H + H (1.12) Being fast and reversible, PTs are typically thermodynamically controlled. In other words, for complete PT to occur, the proton donor must be a stronger acid than the protonated proton acceptor. Stated differently, a proton wants to be bonded to the strongest base around. Tables of pKa values are thus well suited for predicting the direction of PT reactions. 1.9 ELEMENTARY ASSOCIATIVE AND DISSOCIATIVE PROCESSES (A AND D) Two other elementary polar reactions are worth mentioning right away. These are the polar association (A) and dissociation (D) reactions. An A reaction is simply a bond formation between a nucleophile (Nu or Nu− ) or Lewis base and an electrophile (E or E+ ) or Lewis acid, and the product may be positively or negatively charged or neutral: − Nu E − Nu E Nu E Nu E + + Nu E Nu − E (1.13) + Nu E + Nu − E An A reaction is one of the most common elementary reactions (i.e., a one-step process) we will encounter in this book. Whenever you encounter a reaction of the type “A + B → products,” there is a good chance that the first step is either an SN 2 or an A reaction. Indeed, for elements below period 2 of the periodic table, A reactions are at least 17 1.9 ELEMENTARY ASSOCIATIVE AND DISSOCIATIVE PROCESSES (A AND D) as common as SN 2 reactions. Several examples of A reactions involving various p-block elements are shown below: R1 + O (a) − C − B R3 R2 Si Cl H (c) Pb AcO H − F (d) Cl Cl Cl − +O H AcO − F F F F Pb OAc 2− OAc (1.14) − F Sb F F F F I H F F F (e) + O OAc F F Cl Si Cl OAc OAc Sb R2 R3 Cl F F B Cl OAc O O + O C Cl − Cl (b) R1 F F − I F F F F F F F F F A D reaction is the reverse of an A reaction; in other words, a D reaction consists of the heterolytic cleavage of a molecule or ion into a nucleophile–electrophile pair, as shown below: Nu E Nu Nu − E Nu − − + E + + E + Nu E Nu + E + Nu − E Nu + E + (1.15) A classic example of a D reaction is the ionization of t-butyl tosylate in a polar solvent: Me Me + OTs Me Me Me − Me + OTs (1.16) 18 A COLLECTION OF BASIC CONCEPTS A more “inorganic” example might be the ionization of Martin sulfurane, a rather fancy tetravalent-sulfur-based dehydrating agent (discussed in Section 6.13): RF O RF Ph S O Ph − + + S Ph Ph (1.17) O O RF RF A very common pathway for main-group elements is an A–D sequence. Thus, a nucleophile and an electrophile come together to form a complex which then falls apart to a different nucleophile–electrophile pair. The following fluoride ion transfer, ClF3 + AsF5 → [ClF2 ]+ [AsF6 ] – (1.18) a reaction typical of halogen fluorides, is a good example of the two-step process: F F F F Cl Cl +F F F F As F A F F F F F F − F As F F D Cl + + F F F − F As F F (1.19) The D–A sequence is also fairly common. Possibly the best known example of such a sequence is the SN 1 pathway of organic chemistry, briefly described in the next section. A fascinating situation arises when a Lewis base and a Lewis acid are too sterically encumbered to form a bond with each other, as in the example below: F F F F F F t-Bu P t-Bu t-Bu + F F B F F F F F F F No reaction (1.20) 19 1.10 TWO-STEP IONIC MECHANISMS: THE SN 2-Si PATHWAY Very recently, such “frustrated Lewis acid–base pairs (FLPs),” as they are called, have been found to exhibit unique reactivity, including activation of molecular hydrogen (see Section 2.6 for additional details). The following example shows associative (A) reactions between a P/B-based FLP and CO2 . F F F F F F F CO2 B P F F F + P B − − CO2 F F O O F F F F F F F F (1.21) The mechanism presumably consists of two successive association processes, as shown below: Ar Ar O P C B O Ar′ Ar′ Ar Ar O Ar′ Ar′ −B P C O + (1.22) Ar Ar P + C −B Ar′ Ar′ O O Sulfur dioxide also reacts in much the same way with a P,B-based FLP. Feel free to sketch it out. 1.10 TWO-STEP IONIC MECHANISMS: THE SN 2-Si PATHWAY Unlike in organic chemistry, nucleophilic attack on a main-group center with a noble gas configuration does not necessarily lead to immediate bond breakage. This is because of the tendency of p-block elements in period 3 and below to form hypervalent molecules (“expanded octets”). In other words, direct SN 2 displacements (such as the Williamson ether synthesis in reaction 1.1) are far from being the norm for heavier main-group centers. Instead, an incoming nucleophile often adds first, and the leaving group departs only in the next step—in essence, an A–D sequence, to use the terminology of the last section. 20 A COLLECTION OF BASIC CONCEPTS Silylation of an alcohol, a common method for OH group protection in organic chemistry, typically involves such a mechanism: ROH + Me3SiCl Pyridine (1.23) ROSiMe3 The first step is thus an addition: H H Me O Si Cl Me R Me +O R Me Me Si − (1.24) Cl Me The chloride leaves only in a second or later step, as shown below: N H Me Me +O Si − Cl − − Cl + NH + O R Me Me Si (1.25) Me Me R The overall two-step or multistep mechanism is often called SN 2-Si, as this process has been particularly well explored for Si-containing molecules. In this book, we often assume that the SN 2-Si mechanism is operative, especially for higher-valent p-block compounds. 1.11 TWO-STEP IONIC MECHANISMS: THE SN 1 AND E1 PATHWAYS Certain carbon–heteroatom bonds may ionize, especially in polar protic media (sometimes referred to as solvolytic conditions), to generate carbocations. This is shown below for t-butyl tosylate in acetic acid: H3C H3C H H C C H OTs H3 C − − OTs H H + C CH3 (1.26) C H This rate-determining D step forms the first step of both the SN 1 and E1 pathways. In SN 1 (substitution, nucleophilic, unimolecular), the carbocation combines with a nucleophile, often derived from the solvent. In E1, a base, again often derived from the solvent, deprotonates the carbocation and generates an alkene. In this case, the nucleophile or base is the acetate anion (AcO− ): 1.11 TWO-STEP IONIC MECHANISMS: THE SN 1 AND E1 PATHWAYS H3C SN1 H3C H H + C H H − OAc − C H3C H3C CH3 OAc C OAc H H H CH3 C H H3C C − OAc H + C 21 E1 H (1.27) + C − HOAc C H H3C CH3 C H H − CH3 C H OAc Observe that an SN 1 reaction consists of a two-step D–A sequence, whereas an E1 reaction is a D–PT sequence. Because the carbocation carbon is planar (sp2 ), the A reaction with the nucleophile (in this case, AcO− ) can occur via both the front and back sides. Unlike an SN 2 reaction, therefore, an SN 1 reaction is not stereospecific. We will encounter carbocations again several times in this book, so this is a good place for a brief refresher on carbocation stability. Carbocations are described variously as methyl, primary (1∘ ), secondary (2∘ ), or tertiary (3∘ ), depending on the number of alkyl (or aryl) groups attached to the cationic center. The stability of these cations increases in the following order (3∘ most stable): H H + C H H H H C + C < C H + C < H H H H H H H H C H H < C H 2° H + C H 1° H C H C H H 3° This stability order is typically explained in terms of hyperconjugation, which refers to the overlap of neighboring C–H bonds with the empty p orbital at the cationic center, as shown below: + H CH3 H H3C H The phenomenon is also often depicted in terms of “no-bond” resonance structures: + H C H H3C + C H CH3 H C H H3C C CH3 H 22 A COLLECTION OF BASIC CONCEPTS The same phenomenon also explains the enhanced stability of 𝛽-silyl- and 𝛽-stannylsubstituted carbocations: + Si Si C + C C C Lone-pair-bearing heteroatoms strongly stabilize carbocations via resonance or 𝜋-overlap, as shown below: R1 C H + R2 R2 C O H + R1 R1 O + CH H R2 O 1.12 ELECTROPHILIC ADDITION TO CARBON–CARBON MULTIPLE BONDS From an inorganic perspective, this is not an important class of reactions for the simple reason that multiple bonds, particularly homonuclear multiple bonds, are relatively rare in inorganic chemistry. Nevertheless, in the interest of a relatively complete picture of polar mechanisms, a brief summary of these reactions seems appropriate. Consider the addition of an acid HX to an alkene such as 2-methylpropene. The first step involves the creation of a carbocation; note that a 3∘ carbocation is preferentially formed. The carbocation then reacts with X− (in an A reaction) to generate the final product. The overall process is essentially the E1 reaction run in reverse: CH3 − X jor CH3 H H C H3C C X Ma Mi C CH3 + C H3C H H X H3C C C H H H 3° Carbocation H More substituted C–X product H H no r H H3C H3C C + C H 1° Carbocation H H3C − X H3C C C H X H Less substituted C–X product (1.28) The regioselectivity of the reaction, namely, the fact that the more substituted addition product forms preferentially, is commonly referred to as Markovnikov’s rule. 23 1.13 ELECTROPHILIC SUBSTITUTION ON AROMATICS: ADDITION–ELIMINATION Addition of halogen molecules to double bonds is often stereospecific, and the two halogen atoms typically add to opposite faces of the double bond (so-called anti addition). This is explained by the intermediacy of cyclic halonium ions, as shown below: Br + Br Br H3C C H C CH3 Anti addition H3C H H Z C C Br CH3 C H − Br H3C CH3 H3C H H + C C Br H + Br Br H C E H3C Anti addition C H H CH3 Racemic Br H3C Br Br C H CH3 C H Br H C − Br C CH3 H3C H Br CH3 C H3C Br Br C H C H CH3 Meso (1.29) Recall that a racemic substance is an equal mixture of two enantiomers of a chiral molecule. A meso compound, on the other hand, has a symmetry element such as a mirror plane or an inversion center that prevents it from being chiral. Analysis of product stereochemistry thus played a crucial role in establishing these mechanisms. In other cases, addition takes place across a given face of a carbon–carbon double bond (so-called syn addition). Epoxidation by a peroxyacid is a good example: O O + − RCOOH O R H3C H O CH3 H H Z Meso O + O R O O − RCOOH O H H3C H H + H H3C CH3 CH3 H E Racemic (1.30) Once again, product stereochemistry provides key clues to the mechanism. Another important example of syn addition is osmium tetroxide-mediated cis-dihydroxylation of alkenes. Because of their limited relevance in this book, however, we won’t discuss the mechanistic details of these reactions, but do consult your organic text if you are curious. 1.13 ELECTROPHILIC SUBSTITUTION ON AROMATICS: ADDITION–ELIMINATION Electrophiles may add to aromatics, generating transient cationic intermediates. The driving force to regain aromaticity, however, is typically too strong for subsequent addition of a 24 A COLLECTION OF BASIC CONCEPTS nucleophile. Instead, a proton is eliminated, resulting in a substituted aromatic as the final product. The overall two-step process is depicted below for the nitration of benzene, with the nitronium ion (NO2 + ) as the electrophile: O O N+ + H O N + O O −H − N + + O − (1.31) Qualitatively similar mechanisms may be written for a host of other electrophilic substitutions such as sulfonation, halogenation, Friedel–Crafts alkylation and acylation, and thallation. Weaker electrophiles such as molecular halogens and alkyl halides may need activation by a Lewis acid such as AlCl3 , as shown below, a point we will discuss in Section 3.1: R RCl, AlCl3 (1.32) 1.14 NUCLEOPHILIC ADDITION TO CARBON–HETEROATOM MULTIPLE BONDS In this section, we will focus primarily on nucleophilic additions to carbonyl groups. The carbonyl substrate may be an aldehyde or ketone, as well as various carboxylic acid derivatives such acid halides and esters. Among the variety of nucleophiles that can participate in these reactions are hydride, hydroxide, alkoxide, and a variety of carbon-based nucleophiles. For carbonyl substrates, attack by a nucleophile typically results in an opening up of the C–O 𝜋-bond, leading to a tetrahedral intermediate, as shown below for the addition of cyanide to a ketone in the presence of water. − C N N R 1 C C O C R1 R2 − O (1.33) R2 The anionic alkoxide intermediate picks up a proton from water to generate the “cyanohydrin” product: N N C C R1 R2 − O O H H C C R1 R2 − OH + HO (1.34) 25 1.14 NUCLEOPHILIC ADDITION TO CARBON–HETEROATOM MULTIPLE BONDS A similar reaction may also be accomplished under nonaqueous conditions with trimethylsilyl cyanide. Though exceedingly unstable by themselves, trimethylsilyl cations in complexed form may be profitably viewed as “fat protons” and are excellent Lewis acids: N R 1 O + Me3Si C C N SiMe3 C OTf Me3Si (cat.) C R1 R2 (1.35) O R2 The interaction between the carbonyl compound and the catalyst, trimethylsilyl triflate, may be envisioned as an A–D sequence, as shown below: R1 C − Me3Si R1 OTf Me3Si C O OTf R1 O + C R2 R2 SiMe3 O + + − OTf R2 (1.36) A second A–D sequence involving the triflate anion and trimethylsilyl cyanide may then produce free cyanide: N − TfO N C C Me3Si TfO TfO − SiMe3 SiMe3 + − N (1.37) C The cyanide would then attack the activated carbonyl group to yield a silylated cyanohydrin as the final product, as shown below: N − C N R1 C R2 + O SiMe3 SiMe3 C C R1 (1.38) O R2 It’s also conceivable that the actual nucleophile is the five-coordinate species [Me3 Si(CN)(OTf)]− , as opposed to free cyanide. Ester hydrolysis, an important organic reaction that is also of great biological importance, may be either acid- or base-catalyzed. The base-mediated process may be represented as follows: R1COOR2 + NaOH R1COONa + R2OH (1.39) The various oxygens have been colored so you may track how they start from a given starting material and end up in a given product. In practice, the color corresponds to the possible 26 A COLLECTION OF BASIC CONCEPTS use of an isotopic label, typically 18 O. Thus, use of Na18 OH/H2 18 O leads to the incorporation one atom of 18 O into the carboxylic acid product, suggesting that ester cleavage occurs across the R1 CO–OR2 bond, as shown below: − O O R2 C R1 R1 HO O − OH O R2 C R1 O R 1 − O H C + C O OH − O R2 O R2 C O R1 − O + R2 O H (1.40) 18 OH− R2 simply done an SN 2 attack on the group, the label would have been Had the found in the alcohol product. The mechanism shown above is by far the most common mode of ester cleavage, although other modes of cleavage have also been observed for certain substrates and under certain reaction conditions. An important variant of nucleophilic additions to carbonyl compounds is the “conjugate addition” of a nucleophile to the 𝛽-position of an 𝛼,𝛽-unsaturated carbonyl compound. The “enolate” so produced is then protonated, producing a 𝛽-substituted carbonyl compound as the final product. − Nu R O β α − O Nu R R β R R α H A O Nu − −A β α R (1.41) H The most important example of such a conjugate addition is the Michael reaction or Michael addition, which you may remember from your organic course; we also briefly discuss it in the next section. 1.15 CARBANIONS AND RELATED SYNTHETIC INTERMEDIATES In this section, we’ll take a break from our survey of reaction mechanisms and focus instead on a class of intermediates, namely, carbanions. We will also discuss carbanion cognates such as enols, enolates, enamines, and ylides. As classic nucleophiles, carbanions react in highly characteristic ways, particularly via SN 2 displacements, as well as via other pathways (e.g., carbonyl addition and conjugate addition) we have discussed above. The material in this section will thus help you flesh out your understanding of what we have discussed so far. 1.15 CARBANIONS AND RELATED SYNTHETIC INTERMEDIATES 27 The best known among unstabilized carbanionic derivatives are the Grignard reagents (organomagnesium compounds) and organolithiums: RMgBr RLi Alkylsodiums and alkylpotassiums are considerably more reactive and are less commonly used. Of particular importance are stabilized carbanions derived from deprotonation of C–H bonds adjacent to carbonyl groups; such anions are often referred to as enolates because the negative charge is localized more on the carbonyl oxygen than on the carbanionic carbon: − H2C O − O C C R (1.42) R H2C A strong base such as an alkali metal amide (pKa ∼35–40) is typically required to quantitatively convert a simple aldehyde or ketone to an enolate. On the other hand, an alkoxide base (pKa ∼ 16) is sufficient for deprotonating a 𝛽-diketone or a 𝛽-ketoester, since the resulting enolate is much more stabilized by resonance: O O O − O O O − − (1.43) Stabilized carbanions may also be derived from nitriles: H3C − C H 3C C N C H C − N (1.44) H Enamines are an important class of uncharged synthetic intermediates that exhibit carbanion-like reactivity. They are typically prepared from ketones with one or more 𝛼-hydrogens and a secondary amine under acid catalysis: O N H + , − H2O H N (1.45) For reasons of space, we won’t go through the mechanism of this reaction, but do look it up in your organic text, if you wish to. 28 A COLLECTION OF BASIC CONCEPTS Ylides are an important class of carbanion analogs, which we will encounter several times in this book. Generally, they are not anionic, but 1,2-dipolar compounds in which a carbanionic (or other anionic) center is stabilized by an adjacent cationic p-block center, where both centers have full octets of electrons. The best known ylides are phosphonium and sulfonium ylides, the following being prototypical examples: − CH2 P + − H2C Ph Ph Ph Triphenylphosphonium methylide + S Me Me Dimethylsulfonium methylide Carbanions and related intermediates react with a variety of carbon electrophiles, such as alkyl halides and carbonyl compounds, forming carbon–carbon bonds. In this capacity, these intermediates are a cornerstone of organic synthesis. A classic example of a carbanion reaction is the aldol reaction. In this, an enolate reacts with a carbonyl compound to yield a 𝛽-hydroxycarbonyl compound, as shown in the example below: O O − LiNR2 − NHR2 R1 O − O O R − R1 Enolate O H3O 2 R2 − H2O R1 R1 O + HO R1 α β R2 β-Hydroxycarbonyl (1.46) The conjugate addition of an enolate to an 𝛼,𝛽-unsaturated carbonyl compound is called the Michael reaction or Michael addition. A good example is the following, where an enolate derived from diethyl malonate reacts with methyl vinyl ketone. O O O EtO O EtONa (cat.) + EtOH EtO (1.47) EtO Methyl vinyl ketone O Diethyl malonate EtO O We won’t go through the mechanism of this reaction, since it’s essentially the same as that depicted for a generic conjugate addition in Section 1.14. 1.16 CARBENES 1.16 29 CARBENES Divalent carbon species, or carbenes, are another classic group of organic intermediates. Not only are they important in organic chemistry but they are also isoelectronic with other divalent group 14 molecules (based on Ge, Sn, and Pb) and hence of considerable relevance to our further discussions. In addition, nitrogen-stabilized, so-called N-heterocyclic carbenes (NHCs) have gained enormous popularity as transition-metal ligands; many of the resulting complexes mediate unique transformations that define a frontier area of contemporary chemistry. Carbenes occur in one of two low energy states, triplet or singlet. These terms refer to the spin multiplicity of the molecule. The divalent carbon in a triplet carbene has two unpaired electrons, whereas in a singlet carbene the two electrons are paired. Lone-pair-bearing 𝛼-heteroatom substituents strongly stabilize the singlet state, as shown by the 𝜋-type orbital interaction below: Cl H C C H Cl CH2 (triplet) CCl2 (singlet) Cl Cl C + Cl (1.48) + Cl − − C C Cl Cl Two heteroatom substituents can result in highly stable “bottle-able” singlet carbenes, two examples of which are shown below: N N N N R R R R Additional ionic resonance structures, which can also be drawn for these two carbenes (feel free to draw them out), provide a rationale for their stability. Carbenes may be accessed via a variety of routes, of which three common ones are shown below: O O R2 Δ (a) R1 N + N− − N2 R2 R1 30 A COLLECTION OF BASIC CONCEPTS H C (b) Cl − C Base Cl Cl Cl − Cl − C Cl Cl Cl Cl (1.49) (c) R N N + NaH − H2 R R N N R H Observe that the last of these reactions (1.49c) results in the formation of an NHC. A highly characteristic reaction of carbenes is insertion, whereby a carbene inserts itself into a C–H or C–C bond, as shown below: H H H H CH2 H (1.50) H Carbenes also add to double bonds, forming three-membered rings. We’ll have more to say about the reactions of carbenes, particularly carbene analogs, in Chapter 4. 1.17 OXIDATIVE ADDITIONS AND REDUCTIVE ELIMINATIONS We finally come to a pair of reactions that may be described as typically “inorganic”— oxidative addition and reductive elimination. The two processes are the reverse of each other: X Oxidative addition E + X E Y Reductive elimination (1.51) Y Observe that oxidative addition results in an increase in the valence of the element E by two units, while reductive elimination results in the reverse. Thus, oxidative addition is a 1,1-addition, that is, addition of two groups to the same atom. Typical organic additions, by contrast, are 1,2-additions or, less commonly, 1,4-additions. It’s in this sense that oxidative addition and reductive elimination are characteristically inorganic processes. The two processes are common for transition metals and have been studied in considerable depth for many organometallic systems. They are also important for p-block elements. Most p-block elements exhibit multiple valence states, with the valence differing by two units, which makes them suitable candidates for oxidative addition and reductive elimination. 1.17 OXIDATIVE ADDITIONS AND REDUCTIVE ELIMINATIONS 31 Quite a variety of mechanisms are possible for the two processes, including radical pathways. We’ll focus here, however, on just a couple of polar mechanisms. A concerted, one-step mechanism may be written as follows: X X E E (1.52) Y Y Another common pathway involves a two-step polar addition. As written below, the overall process may be viewed as a tandem SN 2–A process: X E Y SN2 − Y X + E A X E (1.53) Y The following chlorination reactions are good examples of oxidative addition involving main-group elements: PCl3 + Cl2 → PCl5 (1.54) ICl + Cl2 → ICl3 (1.55) As in the case of many main-group reactions, the mechanisms have not been investigated for these two reactions. Given that Cl2 is a good electrophile, either of the above mechanisms seems quite reasonable. For reductive elimination, we may envision the reverse of the above two pathways. A concerted, one-step reductive elimination may be depicted as follows: X E + E X (1.56) Y Y Alternatively, we may envision a D–SN 2 sequence: X D E Y + E − Y X SN 2 E + X Y (1.57) 32 A COLLECTION OF BASIC CONCEPTS Good examples of reductive eliminations involving main-group elements include the following: Cl Cl As Cl Cl Cl As + Cl2 Cl Cl Cl (1.58) I Tl + I Ar Ar Tl I I 1.18 MIGRATIONS Migrations are a somewhat quirky process in which an atom or a group tears itself from its site of origin and jumps to a neighboring atom along with its pair of bonding electrons. Thus, typically, the migrating group acts as a nucleophile and the migration terminus as an electrophile. The process is typically intramolecular, that is, occurring within a single covalently bound entity. Some of the best studied examples of migration are provided by carbocation rearrangements. Generally, less stable cations (e.g., 2∘ ) rearrange to more stable ones (3∘ ) by undergoing hydride or alkyl shifts, as shown in the example below: H CH3 C H3C H3C + H3C C C H H3C + CH3 C H (1.59) H Indeed, observation of rearranged products is often seen as “proof ” of the involvement of carbocations and hence of an SN 1/E1-type reaction pathway; concerted SN 2/E2 pathways are not expected to result in a rearrangement. A typical migration involved in a carbocation rearrangement is called a 1,2-shift because the origin and terminus of the migration are (typically, but not invariably) adjacent to each other. We will encounter a few examples 1,2-shifts involving main-group elements. A common reaction pattern is the following: R M − M E E R +L − (1.60) L The migrating group R is often an alkyl or aryl group; the E–L bond is generally weak, which makes L a good leaving group and E a good migration terminus. The negative charge on the migration origin M enhances the migratory aptitude of the R group. Typically, M is a relatively electropositive p-block element such as boron or silicon, or a higher-valent state of an electronegative element such as a halogen. A good example of this type of a 1,2-shift is provided by hydroperoxide-mediated oxidation of organoboranes. 1.19 LIGAND EXCHANGE REACTIONS 33 A standard method of work-up for organoboranes obtained with the hydroboration reaction involves reaction with alkaline hydrogen peroxide. Mechanistically, the first step is an A reaction between the organoborane and a hydroperoxide anion that is present in solution: H R R − O O R B O B (1.61) R R O H R − The anionic boron center then acts as a launchpad for a migrating R group: R O H B R − − OH − B R R O RO HOO − HOO OR − R (1.62) B RO OR Note that the leaving group here is hydroxide, normally a lousy one in organic chemistry. Here, however, the electrophilic site is an oxygen and an O–O bond is a weak one that is easily cleaved. We will encounter several examples of similar 1,2-shifts as we progress through the book. 1.19 LIGAND EXCHANGE REACTIONS Main-group element chemistry is replete with ligand exchange reactions or metatheses. We will encounter a fair number of such reactions in this book, a few examples being as follows: SnCl4 + SnR4 → 2 SnR2 Cl2 (1.63) SO2 + PCl5 → SOCl2 + POCl3 (1.64) 2 (CH3 )3 SiBr + SeCl2 → 2 (CH3 )3 SiCl + SeBr2 (1.65) IF7 + POF3 → IOF5 + PF5 (1.66) For a mechanistic discussion, we will choose the last reaction. A reaction pathway may not be obvious at this point, based on the mechanistic paradigms we have discussed so far. Clearly, a series of simple D and A reactions, whereby oxide and fluoride ligands detach from one central atom and reattach to another one, are unreasonable, given the covalent nature of the molecules involved. An A reaction, however, is still a promising starting point: F F F F + P − O F I F F F F F F O − I F F F F F +P F F F F (1.67) 34 A COLLECTION OF BASIC CONCEPTS The oxo-bridged P+ –O–I− intermediate may now react in a number of different ways. A fluoride could depart from the anionic iodine and reattach to the cationic phosphorus center, as shown below: F F F O F − I F F F +P F F F + P F F F − F I O F F F F I O F F P F F F F F F (1.68) F F F F A second fluoride could then attack the neutral phosphorus center, leading to the final products PF5 and IOF5 : F F O F − F F F I F P F F F O F P F − F F F F F I F F F F (1.69) F F P F + F − O F I F F − + F F F F + F Other pathways are also conceivable for the initially formed oxo-bridged pathway. For example, a 1,3-shift of a fluoride provides “quick” access to the neutral intermediate F4 P–O–IF6 : F F F O + P F − I F F F F F F F O F F F F I F P F (1.70) F F F A second fluoride 1,3-shift, along with cleavage of the I–O bond, could then lead to the final observed products. F F F O F F I P F F F F F P F F F F F F + F − O I + F F F (1.71) 1.20 RADICAL REACTIONS 35 At present, we do not know whether fluoride 1,3-shifts provide a low energy pathway or not. Therefore, we cannot state categorically which of the above two pathways, or for that matter a different one, is the one that operates in reality. Note that both pathways require the formation of an oxo-bridged intermediate. That appears to be a general feature of ligand exchange reactions of this type. When dealing with such reactions, simply join up the two reactants via a lone pair on one of the migrating groups; subsequent D and A reactions, or ligand 1,3-shifts, would then lead to the final products. A word is in order on the thermodynamic driving forces underlying the above reaction. Relief of steric strain at the 7-coordinate iodine is a possible factor, but the main driving force is undoubtedly the formation of two highly stable P–F bonds, whose combined BDEs (∼490 kJ/mol each) more than outweigh that of one P+ –O− unit (∼544 kJ/mol). 1.20 RADICAL REACTIONS Although our focus is clearly on polar or ionic mechanisms, we should not and will not ignore radical pathways altogether. A very brief introduction is therefore provided here. Observe that, in the discussion below, single-headed fishhook arrows indicate “movement” of unpaired electrons. Radicals are typically produced by thermal or photochemical homolytic cleavage of a weak single bond: Homolysis: A (1.72) + B A B Homolysis refers to the separation of a bonding electron pair into two unpaired electrons, that is, radicals. Heterolytic mechanisms, by contrast, are characterized by a bond-breaking step where the electron pair constituting the bond leaves with one of the fragments, as shown below: A B A Heterolysis: A A B + − + B + B − + (1.73) The term “heterolytic mechanism” is thus more or less synonymous with a polar or ionic mechanism. Some classic radical-generating reactions are as follows: (a) Br Br + Br Br R (b) O O 2 RO (1.74) R R (c) N R N 2R + N N 36 A COLLECTION OF BASIC CONCEPTS Let us work our way through a radical chain reaction. A good example is the photochemical chlorination of alkanes, shown below for methane: Cl2, hν CH4 CH3Cl − HCl Cl2 Cl2 (1.75) Cl2 CHCl3 − HCl CH2Cl2 − HCl CCl4 − HCl The reaction begins with the light-induced splitting of molecular chlorine into chlorine atoms; this is called the initiation step: Cl hν Cl + Cl Cl (1.76) A chlorine atom can then abstract a hydrogen from methane: + C H C H H Cl H H H Cl (1.77) H H The methyl radical then abstracts a chlorine atom from molecular chlorine, forming chloromethane and another chlorine atom, thus perpetuating the presence of chlorine radicals in the system. H Cl Cl H C Cl + Cl C H H H (1.78) H The above two steps are collectively referred to as propagation steps. A methyl radical and a chlorine atom may also combine to form chloromethane, as shown below, in what is called a termination step: Cl H H C H (1.79) Cl C H H H Depending on the supply of molecular chlorine, the entire process may continue, leading to further chlorination of chloromethane, ultimately leading to carbon tetrachloride: Cl Cl H C H H C Cl Cl Cl Cl (1.80) 1.21 PERICYCLIC REACTIONS 37 Although much less commonly used in chemical synthesis relative to polar reactions, radical reactions nonetheless form a distinct “genre” of synthetic reactions. Creatively orchestrated, they can lead to a variety of complex structures with a surprising degree of efficiency. 1.21 PERICYCLIC REACTIONS Pericyclic reactions, most notably the Diels–Alder reaction, other cycloadditions, and certain sigmatropic rearrangements in which two or more electron pairs move in a more or less concerted manner along a cyclic pathway are a cornerstone of organic synthesis. Much of their importance derives from the efficiency with which they create two or more bonds in one step and also in a stereospecific manner. Some examples are as follows: Y Y Z Z Diels–Alder: Diene Dienophile Y Y Ene: Z Z H Ene Enophile U 1,3-Dipolar addition: U Y + V W (1.81) H − Z V W Y Z Dipole Dipolarophile Pericyclic reactions provide some of the most elegant examples of the importance of orbital symmetry in chemical reactions. Unlike in organic chemistry, however, pericyclic reactions are not of great importance in inorganic chemistry. That said, we will encounter a few significant examples in this book, including the reduction of carbon–carbon double bonds by diimide (Section 5.7a) and certain selenium dioxide oxidations (Section 6.16). ♦♦♦ That concludes our survey of the major reaction types that we are likely to encounter in this book. We are therefore in a position now to think in somewhat more general terms about arrow pushing. This we do in the next two sections. ♦♦♦ 38 A COLLECTION OF BASIC CONCEPTS 1.22 ARROW PUSHING: ORGANIC PARADIGMS Organic chemists have codified a number of rules and guidelines as aids to arrow pushing. We’ll summarize a few of them here as a starting point for exploring the more diverse world of inorganic mechanisms. 1. Stable molecules, the final products of reactions, typically have noble gas configurations on all atoms, that is, octets on all atoms B through F. 2. Nucleophilic attack on a center with an inert gas configuration (an octet) must lead to bond breakage, that is, departure of a leaving group. 3. Stable organic molecules strive toward charge neutrality for all atoms, although charged species such as carbocations may arise as intermediates. Like charges on two adjacent atoms are a taboo in organic chemistry! 4. Good leaving groups are relatively nonnucleophilic and nonbasic. Thus, N2 is a superb leaving group, and water (H2 O) and alcohols (ROH) are very good leaving groups as well. By contrast, OH− and RO− are lousy leaving groups and H− (hydride) and R− (alkyl anions) are far worse. For us, the key question is: how well do these guidelines carry over to inorganic chemistry? Not too well, it turns out, as we discuss below! 1.23 INORGANIC ARROW PUSHING: THINKING LIKE A LONE PAIR Generally speaking, the mechanisms of p-block element reactions are not particularly consistent with the rules outlined above. The reason for this boils down to the so-called first-row anomaly, where both first- and second-period elements (H–Ne) are all somewhat unreasonably lumped together as first row. The expression means that the chemical properties of first-row elements are anomalous relative to those of their heavier congeners. Let us go through the above four rules one by one and see how well they hold up in a main-group inorganic context. 1. The octet rule breaks down routinely as soon as one goes down to period 3. Main-group centers with more than eight electrons in their valence shells abound for period 3 and below. Molecules containing such centers are called hypervalent. Well-known examples include SiF6 2− , PF5 , PF6 − , SF4 , SF6 , BrF3 , IF5 , IF7 , XeF2 , XeF4 , XeF6 , and XeF8 2− . Even this short list of paradigmatic examples should show with complete clarity that hypervalent molecules are anything but unusual; they are ubiquitous for p-block elements in period 3 and below. Not surprisingly, therefore, the octet rule is essentially irrelevant for these elements. (Note: The bonding in the hypervalent molecules listed above might seem puzzling at first sight, but we will address that issue over the next few sections.) 2. As mentioned in Section 1.9, nucleophilic attack on a heavier main-group center with a noble gas configuration does not necessarily lead to immediate bond breakage. Instead, the first step may be an A reaction leading to a hypervalent intermediate with an expanded octet. The leaving group would them depart in a subsequent D process. As mentioned, this two-step process is known as SN 2-Si. In this book, we have 1.23 INORGANIC ARROW PUSHING: THINKING LIKE A LONE PAIR 39 often tacitly assumed that the SN 2-Si mechanism is operative. Although there is no question that it is pervasive, whether it applies near-universally to all heavier p-block scenarios has yet to be settled. 3. Compared with organic chemistry, charged centers are much more common in main-group element chemistry. Thus, monatomic anions such as O2− , S2− , and N3− are all stable species when stabilized by cations in a solid lattice. Ammonium, phosphonium, and sulfonium ions are an important part of the chemistry of the elements in question. Oxoanions are an important part of the chemistry of the great majority of p-block elements. Thus, rule no. 3 (concerning charge-neutral reactants and products) applies rather more weakly in inorganic chemistry than in organic chemistry; there are many exceptions. 4. We mentioned that strong bases such as OH− and RO− generally make poor leaving groups. These, however, are “poor leaving groups” only from an organic perspective, that is, where the reaction center is carbon. Non-carbon p-block centers vary hugely in their electronegativity from near-metallic or metalloidal B, Al, Sn, and so on, to highly electronegative elements such as N, O, and F. Indeed, for N, O, or halogen reaction centers, OH− and RO− are rather good leaving groups. The reason for this is that bonds between two highly electronegative atoms are weak and are readily broken, both via SN 2 displacements as well as homolytically. Rule no. 4 too thus has limited application in inorganic chemistry. Organic paradigms accordingly are not very helpful in providing rules of thumb for arrow pushing in main-group inorganic chemistry, especially for elements below period 2. Yet we are far from helpless. Simple pattern recognition skills, along with some basic ideas about nucleophiles, electrophiles, and leaving groups, go a long way in helping us arrive at reasonable mechanisms for reactions involving main-group elements. Our approach may be summarized as follows: 1. Look at the product structure(s) carefully and determine what bonds have been broken in the course of the reaction and what new bonds have been formed. 2. Identify the nucleophile and the electrophilic site of attack. 3. Apply steps (1) and (2) iteratively until you arrive at the product structures (assuming they are known). Step (1) consists of pattern recognition, somewhat similar to the logic involved in putting together a puzzle. Note that in the quote at the beginning of the chapter, Sherlock Holmes describes this ability to “reason backward” as easy! Based on many years of experience, we would echo the same assessment. Step (2) is where your chemistry knowledge comes in handy: Apply your knowledge of nucleophilicity, electrophilicity, leaving groups, bond strengths (e.g., bonds between two electronegative atoms are easily cleaved), and so on. Beyond that, we do not advocate an overly algorithmic approach. Several of the reactions discussed in this book are too complex for that. To us, a semi-intuitive approach is what makes inorganic arrow pushing both challenging and fun. Follow your nose! Or, to use our favorite metaphor: think like a lone pair! Where would you attack if you were a lone pair? ♦♦♦ 40 A COLLECTION OF BASIC CONCEPTS It’s time now to think about hypervalent compounds. You have encountered a few of them already, as products of A reactions and as intermediates in SN 2-Si mechanisms. But what is special about such compounds? Is the term “hypervalent” synonymous with higher-valent? (No.) To better understand these issues, we’ll take a step back in Section 1.24 and remind ourselves what the term “valence” exactly means and how it differs from related concepts such as coordination number (CN), FC, and oxidation state