Advanced Organic Chemistry FIFTH EDITION Part A: Structure and Mechanisms Advanced Organic Chemistry PART A: Structure and Mechanisms PART B: Reactions and Synthesis Advanced Organic Chemistry FIFTH EDITION Part A: Structure and Mechanisms FRANCIS A. CAREY and RICHARD J. SUNDBERG University of Virginia Charlottesville, Virginia 123 FrancisA.Carey RichardJ.Sundberg DepartmentofChemistry DepartmentofChemistry UniversityofVirginia UniversityofVirginia Charlottesville,VA22904 Charlottesville,VA22904 LibraryofCongressControlNumber:2006939782 ISBN-13:978-0-387-44897-8(hardcover) e-ISBN-13:978-0-387-44899-3 ISBN-13:978-0-387-68346-1(softcover) Printedonacid-freepaper. ©2007SpringerScience+BusinessMedia,LLC All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connectionwithanyformofinformationstorageandretrieval,electronicadaptation,computersoftware,or bysimilarordissimilarmethodologynowknoworhereafterdevelopedisforbidden. Theuseinthispublicationoftradenames,trademarks,servicemarksandsimilarterms,eveniftheyare notidentifiedassuch,isnottobetakenasanexpressionofopinionastowhetherornottheyaresubject toproprietaryrights. 9 8 7 6 5 4 3 2(corrected2ndprinting,2008) springer.com Preface This Fifth Edition marks the beginning of the fourth decade that Advanced Organic Chemistryhasbeenavailable.Aswiththepreviouseditions,thegoalofthistextisto allowstudentstobuildonthefoundationofintroductoryorganicchemistryandattain a level of knowledge and understanding that will permit them to comprehend much of the material that appears in the contemporary chemical literature. There have been major developments in organic chemistry in recent years, and these have had a major influence in shaping this new edition to make it more useful to students, instructors, and other readers. The expanding application of computational chemistry is reflected by amplified discussion of this area, especially density function theory (DFT) calculations in Chapter 1. Examples of computational studies are included in subsequent chapters that deal with specific structures, reactions and properties. Chapter 2 discusses the principles of both configuration and conformation, which were previously treated in two separate chapters. The current emphasis on enantioselectivity, including devel- opment of many enantioselective catalysts, prompted the expansion of the section on stereoselective reactions to include examples of enantioselective reactions. Chapter 3, which covers the application of thermodynamics and kinetics to organic chemistry, hasbeenreorganizedtoplaceemphasisonstructuraleffectsonstabilityandreactivity. Thischapterlaysthegroundworkforlaterchaptersbyconsideringstabilityeffectson carbocations, carbanions, radicals, and carbonyl compounds. Chapters 4 to 7 review the basic substitution, addition, and elimination mecha- nisms, as well as the fundamental chemistry of carbonyl compounds, including enols and enolates. A section on of the control of regiochemistry and stereo- chemistry of aldolreactionshasbeenaddedtointroducethebasicconceptsofthisimportantarea.A morecompletetreatment,withemphasisonsyntheticapplications,isgiveninChapter 2 of Part B. Chapter8dealswitharomaticityandChapter9witharomaticsubstitution,empha- sizing electrophilic aromatic substitution. Chapter 10 deals with concerted pericyclic reactions, with the aromaticity of transition structures as a major theme. This part of the text should help students solidify their appreciation of aromatic stabilization as a fundamentalconceptinthechemistryofconjugatedsystems.Chapter10alsoconsiders v vi the important area of stereoselectivity of concerted pericyclic reactions. Instructors may want to consider dealing with these three chapters directly after Chapter 3, and Preface we believe that is feasible. Chapters11and12deal,respectively,withfreeradicalsandwithphotochemistry and, accordingly, with the chemistry of molecules with unpaired electrons. The latter chapter has been substantially updated to reflect the new level of understanding that has come from ultrafast spectroscopy and computational studies. As in the previous editions, a significant amount of specific information is providedintablesandschemes.Thesedataandexamplesservetoillustratetheissues thathavebeenaddressedinthetext.Instructorswhowanttoachieveabroadcoverage, but without the level of detail found in the tables and schemes, may choose to advise students to focus on the main text. In most cases, the essential points are clear from the information and examples given in the text itself. We have made an effort to reduce the duplication between Parts A and B. In general, the discussion of basic mechanisms in Part B has been reduced by cross- referencingthecorrespondingdiscussioninPartA.Wehaveexpandedthediscussion ofspecificreactionsinPartA,especiallyintheareaofenantioselectivityandenantios- elective catalysts. We have made more extensive use of abbreviations than in the earlier editions. In particular, EWG and ERG are used throughout both Parts A and B to designate electron-withdrawing and electron-releasing substituents, respectively. The intent is thattheuseofthesetermswillhelpstudentsgeneralizetheeffectofcertainsubstituents such as C=O, C N, NO , and RSO as electron withdrawing and R (alkyl) and RO ≡ 2 2 (alkoxy)aselectronreleasing.Correctuseofthisshorthanddependsonasolidunder- standing of the interplay between polar and resonance effects in overall substituent effects. This matter is discussed in detail in Chapter 3 and many common functional groups are classified. Severalareashavebeentreatedas“Topics”.SomeoftheTopicsdiscussareasthat arestillinaformativestage,suchastheeffortstodevelopDFTparametersasquantitative reactivityindices.Others,suchastheroleofcarbocationsingasolineproduction,have practicalimplications. Wehavealsoabstractedinformationfromseveralpublishedcomputationalstudies to present three-dimensional images of reactants, intermediates, transition structures, andproducts.Thismaterial,includingexercises,isavailableatthepublisherswebsite, andstudentswhowanttoseehowtheoutputofcomputationscanbeappliedmaywant to study it. The visual images may help toward an appreciation of some of the subtle effectsobservedinenantioselectiveandotherstereoselectivereactions.Asinprevious editions, each chapter has a number of problems drawn from the literature. A new feature is solutions to these problems, which are also provided at the publisher’s websiteatspringer.com/carey-sundberg Ourgoalistopresentabroadandfairlydetailedviewofthecoreareaoforganic reactivity. We have approached this goal by extensive use of both the primary and review literature and the sources are referenced. Our hope is that the reader who worksthroughthesechapters,problems,topics,andcomputationalstudieseitherinan organizedcourseorbyself-studywillbeabletocriticallyevaluateandusethecurrent literature in organic chemistry in the range of fields in which is applied, including the pharmaceutical industry, agricultural chemicals, consumer products, petroleum chemistry, and biotechnology. The companion volume, Part B, deals extensively with organic synthesis and provides many more examples of specific reactions. Acknowledgment and Personal Statement The revision and updating of Advanced Organic Chemistry that appears as the Fifth Edition spanned the period September 2002 through December 2006. Each chapter was reworked and updated and some reorganization was done, as described in the Prefaces to Parts A and B. This period began at the point of conversion of library resources to electronic form. Our university library terminated paper subscriptions to the journals of the American Chemical Society and other journals that are available electronically as of the end of 2002. Shortly thereafter, an excavation mishap at an adjacentconstructionprojectledtostructuraldamageandclosureofourdepartmental library.ItremainedclosedthroughJune2007,butthankstotheeffortsofCarolHunter, BethBlanton-Kent,ChristineWiedman,RobertBurnett,andWynneStuart,Iwasable to maintain access to a few key print journals including the Journal of the American Chemical Society, Journal of Organic Chemistry, Organic Letters, Tetrahedron, and TetrahedronLetters.Thesecircumstanceslargelycompletedanevolutioninthesource for specific examples and data. In the earlier editions, these were primarily the result of direct print encounter or search of printed Chemical Abstracts indices. The current editionreliesmainlyonelectronickeywordandstructuresearches.Neithertheformer northelattermethodisentirelysystematicorcomprehensive,sothereisaconsiderable element of circumstance in the inclusion of specific material. There is no intent that specific examples reflect either priority of discovery or relative importance. Rather, they are interesting examples that illustrate the point in question. Several reviewers provided many helpful corrections and suggestions, collated by Kenneth Howell and the editorial staff of Springer. Several colleagues provided valuable contributions. Carl Trindle offered suggestions and material from his course on computational chemistry. Jim Marshall reviewed and provided helpful comments on several sections. Michal Sabat, director of the Molecular Structure Laboratory, provided a number of the graphic images. My co-author, Francis A. Carey, retired in 2000 to devote his full attention to his text, Organic Chemistry, but continued to providevaluablecommentsandinsightsduringthepreparationofthisedition.Various usersofprioreditionshaveprovidederrorlists,and,hopefully,thesecorrectionshave vii viii been made. Shirley Fuller and Cindy Knight provided assistance with many aspects of the preparation of the manuscript. Acknowledgment This Fifth Edition is supplemented by the Digital Resource that is available at andPersonalStatement springer.com/carey-sundberg. The Digital Resource summarizes the results of several computationalstudiesandpresentsthree-dimensionalimages,comments,andexercises based on the results. These were developed with financial support from the Teaching TechnologyInitiativeoftheUniversityofVirginia.Technicalsupportwasprovidedby Michal Sabat, William Rourk, Jeffrey Hollier, and David Newman. Several students made major contributions to this effort. Sara Higgins Fitzgerald and Victoria Landry created the prototypes of many of the sites. Scott Geyer developed the dynamic representations using IRC computations. Tanmaya Patel created several sites and developedthemeasurementtool.Ialsogratefullyacknowledgethecooperationofthe original authors of these studies in making their output available. Problem Responses have been provided and I want to acknowledge the assistance of R. Bruce Martin, DavidMetcalf,andDanielMcCauleyinhelpingworkoutsomeofthespecifickinetic problems and in providing the attendant graphs. It is my hope that the text, problems, and other material will assist new students to develop a knowledge and appreciation of structure, mechanism, reactions, and synthesis in organic chemistry. It is gratifying to know that some 200,000 students have used earlier editions, hopefully to their benefit. Richard J. Sundberg Charlottesville, Virginia March 2007 Introduction This volume is intended for students who have completed the equivalent of a two-semesterintroductorycourseinorganicchemistryandwishtoexpandtheirunder- standingofstructureandreactionmechanismsinorganicchemistry.Thetextassumes basic knowledge of physical and inorganic chemistry at the advanced undergraduate level. Chapter 1 begins by reviewing the familiar Lewis approach to structure and bonding. Lewis’s concept of electron pair bonds, as extended by adding the ideas of hybridization and resonance, plus fundamental atomic properties such as electroneg- ativity and polarizability provide a solid foundation for qualitative descriptions of trendsinreactivity.Inpolarreactions,forexample,themolecularpropertiesofacidity, basicity,nucleophilicity,andelectrophilicitycanallberelatedtoinformationembodied in Lewis structures. The chapter continues with the more quantitative descriptions of molecular structure and properties that are obtained by quantum mechanical calcula- tions.Hückel,semiempirical,andabinitiomolecularorbital(MO)calculations,aswell as density functional theory (DFT) are described and illustrated with examples. This materialispresentedatalevelsufficientforstudentstorecognizethevariousmethods and their ranges of application. Computational methods can often provide insight into reaction mechanisms by describing the structural features of intermediates and transitionstructures.Anotherpowerfulaspectofcomputationalmethodsistheirability torepresentelectrondensity.Variousmethodsofdescribingelectrondensity,including graphical representations, are outlined in this chapter and applied throughout the remainderofthetext.Chapter2exploresthetwostructurallevelsofstereochemistry— configurationandconformation.Molecularconformationisimportantinitsownright, butcanalsoinfluencereactivity.Thestructuralrelationshipsbetweenstereoisomersand the origin and consequences of molecular chirality are discussed. After reviewing the classicalapproachtoresolvingracemicmixtures,modernmethodsforchromatographic separationandkineticresolutionaredescribed.Thechapteralsoexploreshowstereo- chemistry affects reactivity with examples of diastereoselective and enantioselective reactions,especiallythoseinvolvingadditiontocarbonylgroups.Muchoftoday’swork in organic chemistry focuses on enantioselective reagents and catalysts. The enantio- selectivityofthesereagentsusuallyinvolvesrathersmallandsometimessubtlediffer- ences in intermolecular interactions. Several of the best-understood enantioselective ix