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The Art of Writing Reasonable Organic Reaction Mechanisms & Solutions manual, 2nd Edition - Robert B. Grossman The Art of Writing Reasonable Organic Reaction Mechanisms & Solutions manual, 2nd Edition - Robert B. Grossman The Art of Writing Reasonable Organic Reaction Mechanisms & Solutions manual, 2nd Edition - Robert B. Grossman The Art of Writing Reasonable Organic Reaction Mechanisms & Solutions manual, 2nd Edition - Robert B. Grossman The Art of Writing Reasonable Organic Reaction Mechanisms & Solutions manual, 2nd Edition - Robert B. Grossman
The Art of Writing Reasonable Organic Reaction Mechanisms, Second Edition Robert B Grossman Springer 3879_efm1_pi-xvi 10/22/02 9:57 AM Page i The Art of Writing Reasonable Organic Reaction Mechanisms Second Edition 3879_efm1_pi-xvi 10/22/02 9:57 AM Page ii Springer New York Berlin Heidelberg Hong Kong London Milan Paris Tokyo 3879_efm1_pi-xvi 10/22/02 9:57 AM Page iii Robert B Grossman University of Kentucky The Art of Writing Reasonable Organic Reaction Mechanisms Second Edition 13 3879_efm1_pi-xvi 10/22/02 9:57 AM Page iv Robert B Grossman Department of Chemistry University of Kentucky Lexington, KY 40506-0055 USA rbgros1@uky.edu Library of Congress Cataloging-in-Publication Data Grossman, Robert B., 1964– The art of writing reasonable organic reaction mechanisms / Robert B Grossman—2nd ed p cm Includes bibliographical references and index ISBN 0-387-95468-6 (hc : alk paper) Organic reaction mechanisms I Title QD502.5.G76 2002 547Ј.139—dc21 2002024189 ISBN 0-387-95468-6 Printed on acid-free paper This material is based on work supported by the National Science Foundation under Grant 9733201 Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author and not necessarily reflect the views of the National Science Foundation © 2003, 1999 Springer-Verlag New York, Inc All rights reserved This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer-Verlag New York, Inc., 175 Fifth Avenue, New York, NY 10010, USA), except for brief excerpts in connection with reviews or scholarly analysis Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights Printed in the United States of America SPIN 10872580 www.springer-ny.com Springer-Verlag New York Berlin Heidelberg A member of BertelsmannSpringer ScienceϩBusiness Media GmbH 3879_efm1_pi-xvi 10/22/02 9:57 AM Page v Preface to the Student The purpose of this book is to help you learn how to draw reasonable mechanisms for organic reactions A mechanism is a story that we tell to explain how compound A is transformed into compound B under given reaction conditions Imagine being asked to describe how you travelled from New York to Los Angeles (an overall reaction) You might tell how you traveled through New Jersey to Pennsylvania, across to St Louis, over to Denver, then through the Southwest to the West Coast (the mechanism) You might include details about the mode of transportation you used (reaction conditions), cities where you stopped for a few days (intermediates), detours you took (side reactions), and your speed at various points along the route (rates) To carry the analogy further, there is more than one way to get from New York to Los Angeles; at the same time, not every story about how you traveled from New York to Los Angeles is believable Likewise, more than one reasonable mechanism can often be drawn for a reaction, and one of the purposes of this book is to teach you how to distinguish a reasonable mechanism from a whopper It is important to learn how to draw reasonable mechanisms for organic reactions because mechanisms are the framework that makes organic chemistry make sense Understanding and remembering the bewildering array of reactions known to organic chemists would be completely impossible were it not possible to organize them into just a few basic mechanistic types The ability to formulate mechanistic hypotheses about how organic reactions proceed is also required for the discovery and optimization of new reactions The general approach of this book is to familiarize you with the classes and types of reaction mechanisms that are known and to give you the tools to learn how to draw mechanisms for reactions that you have never seen before The body of each chapter discusses the more common mechanistic pathways and suggests practical tips for drawing them The discussion of each type of mechanism contains both worked and unworked problems You are urged to work the unsolved problems yourself Common error alerts are scattered throughout the text to warn you about common pitfalls and misconceptions that bedevil students Pay attention to these alerts, as failure to observe their strictures has caused many, many exam points to be lost over the years v 3879_efm1_pi-xvi 10/22/02 9:57 AM Page vi vi Preface to the Student Occasionally, you will see indented, tightly spaced paragraphs such as this one The information in these paragraphs is usually of a parenthetical nature, either because it deals with formalisms, minor points, or exceptions to general rules, or because it deals with topics that extend beyond the scope of the textbook Extensive problem sets are found at the end of all chapters The only way you will learn to draw reaction mechanisms is to work the problems! If you not work problems, you will not learn the material The problems vary in difficulty from relatively easy to very difficult Many of the reactions covered in the problem sets are classical organic reactions, including many “name reactions.” All examples are taken from the literature Additional problems may be found in other textbooks Ask your librarian, or consult some of the books discussed below Detailed answer keys are provided in a separate volume that is available for download from the Springer–Verlag web site (http://www.springer-ny.com/ detail.tpl?isbn=0387985409) at no additional cost The answer keys are formatted in PDF You can view or print the document on any platform with Adobe’s Acrobat Reader®, a program that is available for free from Adobe’s web site (http://www.adobe.com) It is important for you to be able to work the problems without looking at the answers Understanding what makes Pride and Prejudice a great novel is not the same as being able to write a great novel yourself The same can be said of mechanisms If you find you have to look at the answer to solve a problem, be sure that you work the problem again a few days later Remember, you will have to work problems like these on exams If you can’t solve them at home without looking at the answers, how you expect to solve them on exams when the answers are no longer available? This book assumes you have studied (and retained) the material covered in two semesters of introductory organic chemistry You should have a working familiarity with hybridization, stereochemistry, and ways of representing organic structures You not need to remember specific reactions from introductory organic chemistry, although it will certainly help If you find that you are weak in certain aspects of introductory organic chemistry or that you don’t remember some important concepts, you should go back and review that material There is no shame in needing to refresh your memory occasionally Pine’s Organic Chemistry, 5th ed (McGraw-Hill, 1987) and Scudder’s Electron Flow in Organic Chemistry (John Wiley & Sons, 1992) provide basic information supplemental to the topics covered in this book This book definitely does not attempt to teach specific synthetic procedures, reactions, or strategies Only rarely will you be asked to predict the products of a particular reaction This book also does not attempt to teach physical organic chemistry (i.e., how mechanisms are proven or disproven in the laboratory) Before you can learn how to determine reaction mechanisms experimentally, you must learn what qualifies as a reasonable mechanism in the first place Isotope effects, Hammett plots, kinetic analysis, and the like are all left to be learned from other textbooks 3879_efm1_pi-xvi 10/22/02 9:57 AM Page vii Preface to the Student vii Errors occasionally creep into any textbook, and this one is no exception I have posted a page of errata at this book’s Web site (http://www.chem.uky.edu/research/grossman/textbook.html) If you find an error that is not listed there, please contact me (rbgros1@uky.edu) In gratitude and as a reward, you will be immortalized on the Web page as an alert and critical reader Graduate students and advanced undergraduates in organic, biological, and medicinal chemistry will find the knowledge gained from a study of this book invaluable for both their graduate careers, especially cumulative exams, and their professional work Chemists at the bachelor’s or master’s level who are working in industry will also find this book very useful Lexington, Kentucky January 2002 Robert B Grossman This page intentionally left blank 3879_efm1_pi-xvi 10/22/02 9:57 AM Page ix Preface to the Instructor Intermediate organic chemistry textbooks generally fall into two categories Some textbooks survey organic chemistry rather broadly, providing some information on synthesis, some on drawing mechanisms, some on physical organic chemistry, and some on the literature Other textbooks cover either physical organic chemistry or organic synthesis in great detail There are many excellent textbooks in both of these categories, but as far as I am aware, there are only a handful of textbooks that teach students how to write a reasonable mechanism for an organic reaction Carey and Sundberg, Advanced Organic Chemistry, Part A, 4th ed (New York: Kluwer Academic/Plenum Publishers, 2000), Lowry and Richardson’s Mechanism and Theory in Organic Chemistry, 3rd ed (New York: Addison Wesley, 1987), and Carroll’s Perspectives on Structure and Mechanism in Organic Chemistry (Monterey CA: Brooks/Cole Publishing Co., 1998), are all physical organic chemistry textbooks They teach students the experimental basis for elucidating reaction mechanisms, not how to draw reasonable ones in the first place Smith and March, March’s Advanced Organic Chemistry, 5th ed (John Wiley & Sons, 2001) provides a great deal of information on mechanism, but its emphasis is synthesis, and it is more a reference book than a textbook Scudder’s Electron Flow in Organic Chemistry (John Wiley & Sons, 1992) is an excellent textbook on mechanism, but it is suited more for introductory organic chemistry than for an intermediate course Edenborough’s Writing Organic Reaction Mechanisms: A Practical Guide, 2nd ed (Bristol, PA: Taylor & Francis, 1997) is a good self-help book, but it does not lend itself to use in an American context Miller and Solomon’s Writing Reaction Mechanisms in Organic Chemistry, 2nd ed (New York: Academic Press, 1999) is the textbook most closely allied in purpose and method to the present one This book provides an alternative to Miller & Solomon and to Edenborough Existing textbooks usually fail to show how common mechanistic steps link seemingly disparate reactions, or how seemingly similar transformations often have wildly disparate mechanisms For example, substitutions at carbonyls and nucleophilic aromatic substitutions are usually dealt with in separate chapters in other textbooks, despite the fact that the mechanisms are essentially identical This textbook, by contrast, is organized according to mechanistic types, not ac- ix Chapter H Me Me H Me O O Me H Me O O Me Me O O O Me O O H O Me O H OH O Me O O H H H Me H O O O H2O HO Me O (a) Compound is obviously made by a Diels–Alder reaction between cyclopentadiene and methyl acrylate Cyclopentadiene is made from the starting material by a retro-Diels–Alder reaction The product is obtained stereoselectively because of endo selectivity in the Diels–Alder reaction ∆ CO2Me CO2Me The starting material is called “dicyclopentadiene” Cyclopentadiene itself is not stable: it dimerizes to dicyclopentadiene slowly at room temperature by a Diels–Alder reaction It does this even though it is not an electron-deficient dienophile, demonstrating the enormous reactivity of cyclopentadiene as a diene in the Diels–Alder reaction (b) LDA is a strong base Compound is obtained from the enolate of by a simple SN2 substitution reaction H O OCH3 – I N(i-Pr)2 OMOM – O OCH3 Now DMSO is treated with NaH, then with 2, then with Zn and NaOH, to give overall substitution of CH3 for CH3O The CH3 group must come from DMSO, so we need to make a new bond between the DMSO C and the C=O carbon NaH is a good base; it deprotonates DMSO to give the dimsyl anion This adds to the carbonyl C, and then loss of MeO– occurs to give the β-ketosulfoxide This is a very good acid (like a 1,3-dicarbonyl), so it is deprotonated under the reaction conditions to give the enolate Workup gives back the β-ketosulfoxide This part of the mechanism is directly analogous to a Claisen condensation Chapter O– H3C O O– NaH S CH3 H3C O– H3C S S CH2– O H3C OCH3 O– NaH H3C O OCH3 S O O– – O– work-up S H H – H3C S O H H H To get to 3, we need to cleave the S–C bond Zn is an electron donor, like Na or Li Electron transfer to the ketone gives a ketyl, which undergoes fragmentation to give the enolate The second electron from the Zn goes to the S leaving group to give MeSO– Workup gives the methyl ketone O– O– O– – H3C S e O H3C S O– H H H H H3C S e– H O– H O– H3C H S O – work-up H O H H H (c) The conversion of to is a [2+2] cycloaddition, the Paterno–Büchi reaction This four-electron reaction proceeds photochemically (d) The conversion of to is an E2 elimination R O C H2 – N(i-Pr)2 R H OH The conversion of to is a Swern oxidation The O of DMSO is nucleophilic, and it reacts with oxalyl chloride Cl– then comes back and displaces O from S to give a S electrophile The OH of is then deprotonated, whereupon it attacks S, displacing Cl– Then deprotonation of a Me group and a retrohetero-ene reaction occur to give the ketone Chapter – O O– H3C S Cl Cl H3C O O Cl Cl O O CH3 S Cl O O CH3 H3C S O CH3 – Cl Cl– + CO2 + CO S H3C CH3 Cl H Et3N H Et3N R H H2 C S R H O H2C CH3 S S H3C O– O H Cl R H CH3 R R O O CH3 The conversion of to is a dissolving metal reduction Number the atoms The key atoms are O1, C2, C6, C10, and C9 Make: none Break: C3–C4 O H 2 Li R O 10 H3C10 R The first step is formation of the ketyl of This species can undergo fragmentation to form the C2–C3 enolate and a radical at C4 A second electron transfer gives a carbanion at C4, which deprotonates NH3 Upon workup, C10 is protonated to give – R O e– R R – O – O H e– ≡ O R Chapter – – O H O O H H NH2 H work-up H+ R R H3C R The conversion of to is a simple hydrolysis of an acetal Acetals are functionally equivalent to alcohols + carbonyls and can be interconverted with them under acidic conditions Several reasonable mechanisms can be drawn for this transformation, but all must proceed via SN1 substitutions H3O+ O OMe O OMe O H H The conversion of to uses PPh3 and I2 The former is a nucleophile, the latter is an electrophile, so + they react to give Ph3P–I The P is attacked by the alcohol to give an O–P bond, and the I– then displaces Ph3PO from C to give the alkyl iodide I Ph3P Ph3P I I PPh3 HO – H+ O Ph3P I– O I H The next reaction is obviously a free-radical chain reaction Initiation: H AIBN SnBu3 SnBu3 CN CN Propagation: O H O SnBu3 H3C I H + H3C I SnBu3 Chapter O O H H H SnBu3 + 10 SnBu3 H3C H3C Finally, conversion of 10 to 11 involves addition of the very nucleophilic MeLi to the ketone; workup gives the alcohol Then E1 elimination promoted by the acid TsOH gives the alkene O H HO CH3 H+ work-up H3C H2O CH3 H H3C CH3 H H3C H3C H H H H H3C H3C 11 H3C (a) The transformation of to (not shown) is a simple deprotonation with LDA, followed by SN2 substitution on Se, displacing –SePh The conversion of to requires making C3–C6 and C4–C6, and breaking C6–S The BuLi deprotonates C6 to give a sulfur ylide This makes C6 nucleophilic It adds to C4, making an enolate and making C3 nucleophilic The enolate at C3 then attacks C6, displacing Me2S to give the product O CH3 SePh H3C S CH3 H3C 5 O CH3 H3C S SePh I– BuLi H3C O C H2 H – CH3 Bu H3C S CH2 H3C SePh Chapter – O O SePh SePh CH3 H3C S H3C CH3 The conversion of to is a free-radical chain process Note two equivalents of Bu3SnH are required Make: C7–C11, Sn–Se8 Break: Se8–C7, C3–C4 Let’s deal with the Se first After initiation, Bu3Sn· abstracts SePh from C7 The C7 radical then adds to C11, giving a radical at C12 which abstracts H from Bu3SnH to regenerate ·SnBu3 The C3–C4 bond still needs to be broken, and C3 and C4 both need to have H attached to them We know that a cyclopropane ring cleaves very easily if a radical is generated at a C attached to it, e.g at C2 We can generate a radical at C2 by having Bu3Sn· add to O1 Then the C3– C4 bond cleaves, making a C4 radical and a tin enolate at C3–C2–O1 The C4 radical abstracts H from Bu3SnH to propagate the chain The tin enolate is protonated upon workup to give O SePh Initiation: cat AIBN 10 4 H3C 12 2 Bu3 SnH O H 11 CH3 10 H3C 12 11 H AIBN CH3 SnBu3 SnBu3 CN CN Propagation: O SePh SnBu3 H3C O H H3C H3C CH2 O H H H3C O H O SnBu3 Bu3 Sn H3C CH3 CH2 Chapter CH3 O H Bu3 Sn 10 Bu3 Sn CH3 O H Bu3 Sn H H2C H3C H3C O H Bu3 Sn CH3 O H CH3 work-up Bu3 Sn H3C H3C H3C CH3 (b) LiAlH4 is a source of very nucleophilic H– It must add to an electrophilic C If you obey Grossman’s Rule, you will see that C4 and C6 in the product have extra H’s Of these two only C6 is electrophilic, because when H– adds to C6, a very stable (aromatic) cyclopentadienyl anion is obtained This anion is protonated at C4 upon workup to give the alcohol (Actually, the anion can be protonated on C3, C4, or C5, but all three isomers are in equilibrium with one another, and only the isomer protonated on C4 is able to undergo the subsequent Diels–Alder reaction.) When the alcohol is oxidized to the ketone, the C9=C10 π bond becomes electron-deficient and electronically suitable to undergo an intramolecular Diels– Alder reaction with the cyclopentadiene to give 10 11 HO CH3 1) LiAlH4 CH3 2) Al(O-i-Pr)3, acetone H H H Al H 10 H CH3 11 12 O CH3 12 CH3 CH3 H CH3 work-up CH3 HO HO H H H H H CH3 CH3 HO Oppenauer CH3 H H CH3 O Chapter 11 (c) Make: C4–C11 Break: C3–C4 The first step is electron transfer to form the ketyl Fragmentation of the C3–C4 bond occurs to give a radical at C4, which can add to C11 to make the C4–C11 bond and put the radical on C12 A second electron transfer gives a carbanion at C12 Upon workup it is protonated, as is C14, to give 1 10 12 O 13 14 – – O – H O – O – H O CH3 11 10 ≡ O H – CH2 e H H 12 H H H3C H 13 14 O 7 e– H 2 LiDBB THF 11 O CH2 work-up H H H H First step Make: C3–O8, C2–C5 Break: C7–O8 O H3C CO2Me OH HO CH3 CH3 H3C cat Rh2(OAc)4 N2 CO2Me O8 The product is a γ,δ-unsaturated carbonyl compound (a 1,5-diene), hinting that the last step is a Claisen rearrangement HO H3C MeO2C HO CH3 O H3C CH3 O MeO2C The diazo compound combined with the Rh(II) salt tells you that a carbenoid is involved The carbenoid can be drawn in the Rh=C form or as its synthetic equivalent, a singlet carbene In either case, C3 can Chapter 12 undergo one of the typical reactions of carbenes, addition of a nucleophile, to form the C3–O8 bond After proton transfer to O4 and loss of [Rh], a Claisen rearrangement can occur to give the product O O O CO2Me Rh(II) H3C OH CO 2Me H3C CO2Me H3C O CH3 OH CH3 OH CO2Me H3C CO2Me H3C OH [Rh] [Rh] CH3 [Rh] N2 HO CO2Me H3C O8 O CH3 CH3 Second step Make C3–C5 Break C2–C5 The reaction proceeds by a 1,2-shift HO CH3 BF3·OEt2 CO2Me H3C O H3C HO CO2Me O8 CH3 CH3 CH3 HO HO CO2Me H3C BF3 CO2Me H3C O O BF3 CH3 H3C CO2Me CH3 O HO work-up CO2Me H3C O BF3 OH Third step Standard ozonolysis with Me2S workup O O O3; Me2S CO2Me H3C HO CO2Me H3C HO CH3 O ~ H+ Chapter 13 The Criegee mechanism should be drawn The initially formed 1,2,3-trioxolane can be split up in two ways, one of which gives the desired aldehyde, but the mechanism can’t stop there O O O O O O O CH3 O O CH3 H3C O O SMe2 O O O O CH3 SMe2 O CH3 SMe2 O O CH3 Fourth step It is not clear whether the ring O is O6 or O7 If the ring O is O6, then make: C2–OMe, C2– O6, C5–OMe, and break: C2–O7 If the ring O is O7, then make: C2–OMe, C5–O7, C5–OMe, and break: C5–O6 O7 H3C HO MeO CO2Me MeOH cat TsOH H3C MeO2C or O OMe OH O6 First step is protonation of one of the carbonyl O’s An intramolecular addition is likely to occur faster than an intermolecular one Because a better carbocation can be formed at C2 than at C5, addition of O7 to O5 is more likely than addition of O6 to C2 O CO2Me H3C O H+ H3C HO O OH O ~ H+ MeO H3C HO CO2Me OH H O OMe H3C HO CO2Me O H OH HO CO2Me OH2 O MeO MeO H3C H3C HO CO2Me H OMe HO CO2Me Chapter 14 H O OMe O MeO MeO H3C H3C HO CO2Me OMe HO CO2Me It should be stressed that this mechanism is not the only reasonable one for this reaction Any reasonable mechanism should avoid an SN2 substitution, however Make: C1–C4, C3–C8 Break: C1–O2, C8–Br The light suggests a free-radical or pericyclic reaction is operative in at least part of the mechanism O Naph CH3 + OH O CH3 t-BuOK hν, liq NH3 Br Naph The base may deprotonate either C3 or C4 Deprotonation of C3 makes it nucleophilic We need to form a new bond from C3 to C8 via substitution The mechanism of this aromatic substitution reaction could be addition–elimination or SRN1 The requirement of light strongly suggests SRN1 See Chap 2, section C.2, for the details of drawing an SRN1 reaction mechanism O O O Naph CH2 CH3 + SRN1 hν, liq NH3 CH3 Naph Br O After the substitution is complete, all that is required is an aldol reaction, dehydration by E1cb, and deprotonation Workup then gives the product Chapter 15 O O CH3 Naph aldol O O E1cb Naph OH O– OH work-up Naph Naph H H Naph H H Alternatively, deprotonation of C4 makes it nucleophilic, and an aldol reaction and dehydration by E1cb gives an enone O O O Naph CH2 + CH3 aldol CH3 E1cb Naph Br Br We still need to form C3–C8 Deprotonation of C3 gives a dienolate The more stable, (E) isomer will form Light causes this isomer to isomerize to the (Z) isomer An electrocyclic ring closing, which may also require light because it destroys aromaticity, gives the C3–C8 bond Expulsion of Br– and deprotonation gives the conjugate base of the product O O– CH3 Naph t-BuOK Naph Br hν Br O– O– O– O hν Br Naph Br Naph Make: C3–C11, N6–C11, C7–C9 Break: C11–O12 Naph Naph H H H Chapter Bn NHBn N H 10 Me 6N 11 12 PhCO2H CO2Me 11 CHO 16 10 Me N H 12 + H2O CO 2Me The combination of an amine and an aldehyde under weakly acidic conditions almost always gives an iminium ion very rapidly Such a reaction forms the N6–C11 bond Nucleophilic C3 can then attack this iminium ion to give a new iminium ion We still need to make C7–C9 Deprotonation of C7 gives a neutral enamine and a 1,5-diene Cope rearrangement of the diene gives the C7–C9 bond, but it breaks the C3–C11 bond that was just formed! However, C11 can be made electrophilic again by protonation of C10 Attack of nucleophilic C3 on C11 gives an iminium ion again, and deprotonation of C7 gives the product H OH NHBn Me N H 11 OH N Bn N H CO2Me CO2Me OH2 NBn 11 N Bn N H Me Me + ~H N H CO2Me CO2Me NBn NBn 11 Me H –H+ H CO2Me N H N H NBn H N H Me Me CO2Me NBn H 10 Me CO2Me H H 11 H+ N H H Me CO2Me ~H+ Chapter 17 NBn H NBn H H H N H H H –H+ H Me CO2Me Me N H CO2Me First reaction Make: N1–C8, C7–C8 Break: C5–Si6, C8–O9 HN Br SiMe2 Ph DbsN ZnI2, EtOH Dbs CHO N N H Br The combination of an amine and an aldehyde under weakly acidic conditions almost always gives an iminium ion very rapidly Such a reaction forms the N1–C8 bond Nucleophilic C7 can then attack this iminium ion to give a carbocation Fragmentation of the C5–Si6 bond gives the product I2Zn Dbs O I2Zn Br Dbs NH N SiMe2 Ph Br N N H ~H+ SiMe2 Ph I2Zn Dbs O Br OH N N N DbsN SiMe2 Ph Br SiMe2 Ph N H N DbsN DbsN SiMe2 Ph Br H Second step Make: C5–C10 Break: C5–Br Br H Chapter 18 2N N DbsN Br cat (Ph3P)2Pd(O2CCF3)2 10 11 10 i-Pr2 NEt H 12 11 12 DbsN The catalytic Pd complex and the aryl bromide together suggest the first step is oxidative addition of Pd(0) to the C5–Br bond (The reduction of Pd(II) to Pd(0) can occur by coordination to the amine, β-hydride elimination to give a Pd(II)–H complex and an iminium ion, and deprotonation of Pd(II)–H to give Pd(0).) The C10–C11 π bond can then insert into the C5–Pd bond to give the C5–C10 bond β-Hydride elimination then gives the C11–C12 π bond and a Pd(II)–H, which is deprotonated by the base to regenerate Pd(0) The overall reaction is a Heck reaction N DbsN N DbsN L2Pd H Br 11 insertion Br N Pd L2 II insertion H N Br H L2Pd II DbsN coordination, 10 H H β -hydride elimination DbsN H + Br H II Pd H L2 NR3 L2Pd [...]... reasonable mechanisms by themselves, not to teach them the “right” mechanisms for various reactions Another important difference between this textbook and others is the inclusion of a chapter on the mechanisms of transition-metal-mediated and -catalyzed reactions Organometallic chemistry has pervaded organic chemistry in recent years, and a working knowledge of the mechanisms of such reactions as metalcatalyzed... provided at the end of the book All of the chapters in this book except for the one on transition-metal-mediated and -catalyzed reactions can be covered in a one-semester course The present second edition of this book corrects two major errors (the mechanisms of substitution of arenediazonium ions and why Wittig reactions proceed) and some minor ones in the first edition Free-radical reactions in Chapter... summary, the characteristics of the three kinds of hybridization are as follows: • sp3 hybridization: The s and all three p orbitals are averaged to make four sp3 orbitals of equal energy The four orbitals point to the four corners of a tetrahedron and are 109° apart The energy of each sp3 orbital is ᎏ34ᎏ of the way from the energy of the s AO to the energy of a p AO • sp2 hybridization: The s and... than either of the two starting AOs The subtractive (out -of- phase) combination, an antibonding MO, is higher in energy than either of the two starting AOs In fact, the destabilization of the antibonding MO is greater than the stabilization of the bonding MO • • • antibonding MO • Energy subtract add • • AO AO bonding MO Why must two AOs interact in both a constructive and a destructive manner? The physical... describe the likelihood of finding a gnat at a particular distance from one’s mouth or nostrils Likewise, the position of particular electrons cannot be defined; instead, a mathematical function called an orbital describes the probability of finding an electron of a certain energy in a particular region of space The actual probability is given by the square of the value of the orbital at a particular... three sp2 orbitals of equal energy, and one p orbital is left unchanged The three hybrid orbitals point to the three corners of an equilateral triangle and are coplanar and 120° apart; the unhybridized p orbital is perpendicular to the plane of the hybrid orbitals The energy of each sp2 orbital is ᎏ23ᎏ of the way from the energy of the s AO to the energy of a p AO • sp hybridization: The s and one p orbital... and they are used as empty orbitals To determine the hybridization of an atom, add up the number of lone pairs not used in resonance and the number of bonds (i.e., atoms to which it is bound) If the sum is four, the atom is sp3-hybridized If the sum is three, it is sp2-hybridized If the sum is two, it is sp-hybridized Problem 1.3 Determine the hybridization of the C, N, and O atoms in each of the. .. sp orbitals of equal energy, and two p orbitals are left unchanged The sp orbitals point 180° apart from each other The two unhybridized p orbitals are perpendicular to each other and to the line containing the sp orbitals The energy of each sp orbital is halfway between the energy of the s AO and the energy of a p AO 3879_a01_p 1-4 9 10/22/02 9:58 AM Page 13 Structure and Stability of Organic Compounds... Molecules are three-dimensional objects, and as such they have shapes You must always keep the three-dimensional shapes of organic compounds in mind when you draw reaction mechanisms Often something that seems reasonable in a flat 3879_a01_p 1-4 9 10/22/02 9:58 AM Page 10 10 1 The Basics drawing will manifest itself as totally unreasonable when the three-dimensional nature of the reaction is considered,... country and around the world for their enthusiastic embrace of the first edition of this book Their response was unexpected and overwhelming I hope they find this new edition equally satisfactory Lexington, Kentucky January 2002 Robert B Grossman 3879_efm1_pi-xvi 10/22/02 9:57 AM Page xiii Contents Preface to the Student Preface to the Instructor 1 The Basics 1.1 Structure and Stability of Organic Compounds