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Eric V. Anslyn 学术报告---《化学选论》系列之二十
日期： 15:03
&题&目&Supramolecular Analytical Chemistry
时&间&2011年06月2日（星期四） 上午9:30&
地&点&玉泉校区 教八-218
报告人& Eric V. Anslyn, &J. Am. Chem. Soc., Associate Editor
单&位&University of Texas
PhD, California Institute of Technology, 19821987
Postdoctor, Columbia University,
Faculty, University of Texas, 1989 (Full Professor from 2004)
Research Interest
&His research encompasses physical organic and bioorganic chemistry, and his research generally explores the use ofsynthetic receptors for sensing and catalysis applications.
1. Chem. Sci. 9-445.
&2. J. Am. Chem. Soc. , 45 .
3. &Chem. Soc. Rev. 21-3632.
&4. J. Am. Chem. Soc. , 13114 &&&&&&&&&&&&&&&&&&&
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&&&&Eric V. Anslyn 教授学术报告
报告题目： Differential Sensing: Concepts and Applications 报 告 人： Eric V. Anslyn 教授 （JACS副主编，The University of Texas at Austin） 时&& &间： （周四）上午10：30 地&&& 点： 教工之家 报告人简介： &&& Professor Eric V. Anslyn is the Associate Editor of J. Am. Chem. Soc. and a Fellow of American Association for the Advancement of Science. He is the recipient of numerous awards and honors, including ACS Edward Leete Award（2013）and ACS Cope Scholar Award（2006）.Dr. Anslyn received his PhD in Chemistry from the California Institute of Technology under the direction of Robert Grubbs. After completing post-doctoral work with Ronald Breslow at Columbia University, he joined the faculty at the University of Texas at Austin, where he became a Full Professor in 1999. He currently is Norman Hackerman Chair of Chemistry at the University of Texas at Austin. He is also known as the author of Modern Physical Organic Chemistry textbook.
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淘豆网网友近日为您收集整理了关于Modern Physical Organic Chemistry, - Chapter6 - Stereochemistry(Eric V Anslyn, Dennis A Dougherty)的文档，希望对您的工作和学习有所帮助。以下是文档介绍：Modern Physical Organic Chemistry, - Chapter6 - Stereochemistry(Eric V Anslyn, Dennis A Dougherty) 297CHAPTER 6StereochemistryIntent and PurposeStereochemistry is the study of the static and dynamic aspects of the three-dimensionalshapes of molecules. It has long provided a foundation for understanding structure and re-activity. At the same time, stereochemistry constitutes an intrinsically interesting researcheld inits own right.Many chemists nd thisarea of studyfascinating due simplyto the aes(来源：淘豆网[/p-3987794.html])-thetic beauty associated with chemical structures, and the intriguing ability bine theelds of geometry, topology, and chemistry in the study of three-dimensional shapes. In ad-dition, there are extremely important practical ramications of stereochemistry. Nature isinherently chiral because the building blocks of life ( -amino acids, nucleotides, and sugars)are chiral and appear in nature in enantiomerically pure forms. Hence, any substances cre-ate(来源：淘豆网[/p-3987794.html])d by humankind to interact with or modify nature are interacting with a chiral environ-ment. This is an important issue for anic chemists, and a practical issue for pharma-ceutical chemists. The Food and Drug Administration (FDA) now requires that drugs beproduced in enantiomerically pure forms, or that rigorous tests be performed to ensure thatboth enantiomers are safe.In addition, stereochemistry is highly relevant to unnatural systems. As we will(来源：淘豆网[/p-3987794.html]) de-scribeherein, thepropertiesofsynthetic polymersareextremelydependent uponthestereo-chemistry of the repeating units. Finally, the study of stereochemistry can be used to probereaction mechanisms, and we will explore the stereochemical e of reactions through-out the chapters in parts II and III of this text. Hence, understanding stereochemistry is nec-essary for most elds of chemistry, making this chapter one of paramount importance.All anic chem(来源：淘豆网[/p-3987794.html])istry courses teach the fundamentals of stereoisomerism,and we will only briey review that information here. We also take a slightly more modernviewpoint, emphasizingnewer terminology andconcepts. The goal isfor the studentto gaina fundamental understanding of the basic principles of stereochemistry and the associatedterminology, and then to present some of the modern problems and research topics in thisarea.6.1 Stereogenicity and StereoisomerismSte(来源：淘豆网[/p-3987794.html])reochemistry is a eld that has often been especially challenging for students. No doubtone reason for this is the difculty of visualizing three-dimensional objects, given two-dimensional representations on paper. Physical models and 3-puter models can be ofgreat help here, and the student is encouraged to use them as much as possible when work-ing through this chapter. However, only simple wedges and dashes are given in most of ourdrawings. It is th(来源：淘豆网[/p-3987794.html])ese kinds of simple representations that one must master, because attrac-tive, computer generated pictures are not routinely available at the work bench. The mon convention is the familiar ‘‘wedge-and-dash’’ notation. Note that there is somevariability in the symbolism used in the literature. Commonly, a dashed wedge that getslarger as it emanates from the point of attachment is used for a receding group. However,considering the art of perspective d(来源：淘豆网[/p-3987794.html])rawing, it makes no sense that the wedge gets bigger as298 CHAPTER 6: STEREOCHEM ISTRYProjecting awayfrom the viewerProjecting towardthe viewerHydrogens projectingtoward the viewerThe convention usedin this bookit moves further away. Yet, this is the mon convention used, and it is the con-vention we adopt in this book. Many workers have turned to a simple dashed line instead(see above), or a dash that does get smaller. Similarly, both a bold wedge a(来源：淘豆网[/p-3987794.html])nd a bold lineare used to represent forward-projecting substituents. mon convention is thebold ‘‘dot’’ on a carbon at a ring junction, representing a hydrogen that projects toward theviewer.The challenge of seeing, thinking, and drawing in three dimensions is not the only causefor confusion in the study of stereochemistry. Another major cause is the terminology used.Hence, we start this chapter off with a review of basic terminology, the problems as(来源：淘豆网[/p-3987794.html])sociatedwith this terminology, and then an extension into more modern terminology.6.1.1 Basic Concepts and TerminologyThere was considerable ambiguity and imprecision in the terminology of stereochemis-try as it developed during the 20th century. In recent years, stereochemical terminology hasclaried. We present here a discussion of the basics, not focused solely on carbon. However,inSection 6.2.4wewillexamine carbonspecically.Whilemost ofthisshould(来源：淘豆网[/p-3987794.html]) bereview,per-haps the perspective and some of the terminology will be new.Let’s start by delineating the difference between a stereoisomer and other kinds of iso-mers. Recall that stereoisomers are molecules that have the same connectivity but differ inthe arrangement of atoms in space, such as cis- and trans-2-butene. Even gauche and anti bu-tane are therefore stereoisomers. This is in contrast to constitutional isomers, which aremolecules with the same molecular formula but different connectivity between the atoms,such as 1-bromo- and 2-bromobutane. The constitution of a molecule is dened by the num-ber and types of atoms and their connectivity, including bond multiplicity. These denitionsare straightforward and clear (as long as we can agree on the denition of connectivity—seethe Going Deeper highlight on page 300).An historical distinction, but one that is not entirely clear cut, is that between congura-tional isomers and conformational isomers. Conformational isomers are interconvertibleby rotations about single bonds, and the conformation of a molecule concerns features re-lated to rotations about single bonds (see Chapter 2). There is some fuzziness to this distinc-tion, attendant with the denition of a ‘‘single’’ bond. Is the C–N bond of an amide a singlebond, even though resonance arguments imply a signicant amount of double bond charac-ter and the rotation barrier is fairly large? Also, some olenic ‘‘double’’ bonds can have quitelow rotation barriers if the appropriate mix of substituents if present. Because of these exam-ples,aswellasotherissuesconcerningstereochemistry, wesimplyhavetolivewithacertainamount of terminological ambiguity. A related term is atropisomers, which are stereoiso-mers that can be interconverted by rotation about single bonds but for which the barrier torotation is large enough that the stereoisomers can be separated and do not interconvertreadily at room temperature (examples are given in Section 6.5).The term congurational isomer is a historic one that has no real value in modern ste-reochemistry. It is generally used to pass enantiomers and disastereomers as isomers(see denitions for these below), but stereochemical isomers is a better term. The term con-2996.1 STER EOGENICITY AN D STEREOISOMER ISMFigure 6.1Simple owchart for classifying various kinds of isomers.Two structureswith the same formulaSameconnectivity?ConstitutionalisomersStereoisomersNon-congruentmirrorimages?DiastereomersEnantiomersyesyesnonoguration is still useful. Mislow denes conguration as ‘‘the relative position or order ofthe arrangement of atoms in space which characterizes a particular stereoisomer’’. A re-lated term is absolute conguration, which relates the conguration of a structure to anagreed upon stereochemical standard. For example, later in this chapter we discuss the dand l nomenclature system, where the arrangement of atoms in space is related to that of( )-glyceraldehyde. If the arrangement of atoms in space in a molecule can be related to( )-glyceraldehyde, or some other standard, we state that we know that molecule’s abso-lute conguration.When two stereoisomers are nonsuperposable mirror images of each other, they areknown as enantiomers (see the schematic examples in the margin). To achieve the mirrorimage of a molecule, simply imagine a sheet of glass placed alongside the molecule of inter-est, then pass each atom through the glass such that each atom ends up the same distancefromthe sheetofglassas intheoriginalstructure. Stereoisomersthatare notenantiomersareknown as diastereomers. Figure 6.1 shows a simple ow chart for classifying isomers.Any object that is nonsuperposable (noncongruent) with its mirror image is chiral. If anobject is not chiral—that is, if its mirror image is congruent with the original—it is achiral.Classic TerminologyThereareaseriesof termsusedinthecontextofstereochemistrythat areingrainedintheliterature, and several you are likely familiar with from anic chemistry. We de-ne many of these terms here, and examine how they can be misleading. After a look at thisclassic terminology, more modern and concise terms are given.Confusion with respect to terminology arises with terms such as ‘‘optically active’’ and‘‘chiral center’’, which often mislead as much as they inform. Optically active refers to theability of a collection of molecules to rotate plane polarized light (a phenomenon that we ex-plore in detail in Section 6.1.3).In order for a sample to be optically active, itmust have an ex-cess of one enantiomer. es the confusion. Optically active was generally used as asynonym for chiral in the earlier literature, and unfortunately this usage continues at timeseventoday.Wediscouragethisuse.Theproblem isthattherearemanyexamplesofchemicalWXZYWSheet of glassXZYZWXYZEnantiomers: non-superimposablemirror imagesV VWXY300 CHAPTER 6: STEREOCHEM ISTRYOHChiral molecules withouta “chiral center”onnectionsStereoisomerism and Connectivity Further, what about metal coordination? We fortable with a clear connectivity pattern in anicA crucial concept in the denition of plexes such as iron pentacarbonyl or a -given above is ‘‘connectivity’’. In methane or 2,3-plex. But what about Mg2+plexing a carbonyl?dichlorobutane, there is no doubt as to the connectivity ofWhen is a bond too weak to be considered relevant forthe system. However, there is an innate arbitrariness to thestereoisomerism?term, and this can lead to some ambiguity about stereo-isomerism. For example, do hydrogen bonds count in ourlist of connectivity? No, but consider the implications ofthis. If hydrogen bonds ‘‘don’t count’’, then how do wethink about isomerism in double-helical DNA? Do we justignore the interaction of the two strands? As a simplerexample, in a solution of a racemic carboxylic acid, doesOMg2+Mg2+Stereoisomers?Odimerization create true diastereomers?Finally, there has been a modern emphasis on ‘‘topo-logical isomerism’’, structures with loops or interlockingrings in which large parts of the molecule are not con-nected to each other in any conventional way. This canproduce novel stereochemical situations, as we will seein Section 6.6.In the end, there is no universally agreed upon con-vention for connectivity as it relates to stereoisomerism.Usually, the connectivity of a system is clear. When thereis the potential for ambiguity, though, a clear statementof the ground rules should be made.H HDo diastereomers exist ina solution of arboxylic acids?O H OO H OH HO H OO H Osamples that contain chiral molecules, but the samples themselves are not optically active. Aracemic mixture, a 50:50 mixture of enantiomers, is not optically active, but every moleculein the sample is chiral. It is important to distinguish between a sample that is optically inac-tive because it contains a racemic mixture and a sample that is optically inactive because itcontains achiral molecules, and the earlier terminology made this difcult.Also, it is easy to imagine molecules, even when enantiomerically pure, that would notrotate plane polarized light to any measurable extent. The extent of rotation of plane polar-ized light depends upon differences in the refractive indices with respect to right and left cir-cularly polarized light as it passes through the sample. Enantiomers that do not have dra-matically different refractive indices would not result in measurable rotations. Exampleswould be a carbon with four different n-alkyl chains attached, with chain lengths of maybe10, 11, 12, and 13 or one with four C10 chains, but terminating in –CH3, –CH2D,–CHD2, and –CD3. In each case the molecule is chiral, but any rotation of plane polarizedlight would be immeasurably small. Operationally, they are optically inactive. Finally, evenan enantiomerically pure sample of a chiral molecule will show zero rotation at certainwavelengths of light, as we move from ( ) rotation to ( ) rotation in the optical rotatory dis-persion (ORD) curve (see Section 6.1.3). ‘‘Optically active’’ is an ambiguous description.More confusion arises with terms that are meant to focus on the chirality at a particularpoint in a molecule. The prototype is the chiral center or chiral carbon, which is dened asan atom or specically carbon, respectively, that has four different ligands attached. Here,the term ‘‘ligand’’ refers to any group attached to the carbon, such as H, R, Ar, OH, etc. Theparticular case of a carbon with four different ligands has also been termed an arbon. One problem with such terms, as we will show below, is that ‘‘asymmetric carbons’’and ‘‘chiral centers/carbons’’ exist in molecules that are neither asymmetric nor chiral. Inaddition, many molecules can exist in enantiomeric forms without having a ‘‘chiral center’’.Classic examples include dimethylallene and the twisted biphenyl shown in the margin—we’ll see more below. Given all this, although the terms may already be part of your vocabu-lary, we discourage their use.3016.1 STER EOGENICITY AN D STEREOISOMER
CSwap two ligandsCHHONH2CO2HSwap two ligandsSwap two ligandsSwap two ligandsSwap two ligandsRu ClH2OClClOH2H2OClClPFFRu ClClClH2OOH2H2OFClClPClFCH3H3CHHC C CH2NHOHCO2HHFigure 6.2Molecules with stereogenic centers. The enters are marked with colored arrows, and a curvedblack arrow is used to show how ligand interchangeat a stereogenic center produces a new stereoisomer.More Modern TerminologyMuch of the confusion that can be generated with the terms given above was eliminatedwith the introduction of the stereogenic center (or, equivalently, stereocenter) as a-nizing principle in stereochemistry. An atom, or a grouping of atoms, is considered to be astereogenic center if the interchange of two ligands attached to it can produce a new stereo-isomer. Not all interchanges have to give a new stereoisomer, but if one does, then the centeris stereogenic. The center therefore ‘‘generates’’ stereochemistry. A non-stereogenic centeris one in which exchange of any pair of ligands does not produce a stereoisomer. The term‘‘stereogenic center’’ is, in a sense, broader than the term ‘‘chiral center’’. It implies nothingabout the molecule being chiral, only that stereoisomerism is possible. The structures in Fig-ure 6.2 show several stereogenic centers. Note that in plex geometries, such aspentacoordinate or hexacoordinate atoms, we do not need all the ligands to be inequivalentin order to have a stereogenic center. Given these new terms, we strongly encourage stu-dents to abandon the term ‘‘chiral center’’ and to reserve ‘‘optically active’’ as a descriptionof an experimental measurement.A related and more passing concept is that of a stereogenic unit. A stereogenicunit is an atom or grouping of atoms such that interchange of a pair of ligands attached to anatom of the grouping produces a new stereoisomer. For example, the C C group of trans-2-butene is a stereogenic unit because swapping a CH3/H pair at one carbon produces cis-2-butene. A tetrahedral atom is a stereogenic unit, where swapping the positions of any two offour different ligands gives a stereoisomer (see below).In the examples of chiral molecules without ‘‘chiral centers’’ noted above, the C C Cunit of the allene and the biphenyl itself are stereogenic units. Many workers have adoptedtermssuch asplanar chiralityand axialchirality todescribe systemssuch aschiral biphenyland allene based structures, respectively. The justication for these terms is that such mole-cules do not have stereogenic centers, but rather stereogenic units. Admittedly, terms thataddress chirality without stereogenic centers could be useful. However, since a moleculethat is truly planar (i.e., has a plane of symmetry) must be achiral, planar chirality is an odduse of the word ‘‘planar’’. Developing precise, unambiguous denitions of these terms is achallenge that, in our view, has not yet been met. Currently, the best term is ‘‘stereogenicunit’’, where the biphenyl or allene groups have the ability to create chirality, just as a tetra-hedral atom has the ability to generate chirality.302 CHAPTER 6: STEREOCHEM ISTRYFigure 6.3Illustration of the concept of the stereogenic center in the contextof carbon. Whether in a chiral molecule like 2-butanol or an achiralmolecule like meso-tartaric acid, interconversion of two ligands ata stereocenter produces a new stereoisomer.(R)-2-Butanol (S)-2-enterInterconverting two ligandsproduces a new stereoisomerH CH3HOHHH3CH CH3HHOHH3Cmeso-Tartaric acid (R,R)-Tartaric enterInterconverting two ligandsproduces a new stereoisomerHO CO2HHOHHHO2CHO CO2HHHOHHO2CTo illustrate the value of the newer terminology, let’s review two prototypes anicstereochemistry. First, consider a molecule that has a carbon with four different ligands, acarbon we will describe as CWXYZ. A specic example is 2-butanol (Figure 6.3). If we inter-change any two ligands at carbon 2, we obtain a stereoisomer—the enantiomer—of the orig-inal structure. Thus, C2 of 2-butanol is a stereogenic center. The analysis can get -plicated in systems with more than one CWXYZ center. Let’s consider such a case.Figure 6.3 also shows tartaric acid. Beginning with the structure labeled ‘‘meso’’, if weinterchange two ligands at either C2 or C3, we obtain a new structure, such as (R,R)-tartaricacid. (If you do not recall the R and S notation, look ahead to Section 6.1.2.) This structure hasthe same connectivity as meso-tartaric acid, but the two are not congruent (verify for your-self), and so the new structure is a stereoisomer of the original. However, (R,R)- and meso-tartaric acid are not mirror images, so they are not enantiomers. They are diastereomers.Note that the meso form of tart verify for yourself that it is congruentwith its mirror image. However, C2 and C3 of meso-tartaric acid are thatis, swapping any two ligands at either center produces a new stereoisomer. This is one valueof the stereogenic center concept. As we noted above, in earlier literature a CWXYZ centersuch as C2 or C3 was called a chiral center, but it seems odd to say we have two chiral centersin an achiral molecule! A CWXYZ center does not guarantee a chiral molecule. However, aCWXYZ group is always a stereogenic center.Tartaric acid has two stereogenic centers and exists as three possible stereoisomers. Thisis an exception to the norm. Typically, a molecule with n stereogenic, tetracoordinate car-bons will have 2nstereoisomers–2n–1diastereomers that each exist as a pair of enantiomers.For example, a structure with two stereogenic centers will exist as RR, SS, RS, and SR forms.In tartaric acid the RS and SR forms are identical—they are both the meso form—because C2and C3 have the same ligands.The2nrulequickly plexity inmoleculeswith multiplestereogenic centers.plex natural products that are often targets of total synthesis efforts, it is conventional tonote the number of possible stereoisomers (for example, 10 stereogenic centers implies 1024stereoisomers), with only bination dening the proper target (see the FollowingConnections highlight). Polymers, both natural and synthetic, can produce extraordinarystereochemical diversity when each monomer carries a stereogenic center. We’ll return tothis issue below.When many stereogenic centers are present in a molecule, it es difcult to refer toall the possible stereoisomers. It is often useful to consider only two different isomers, calledepimers. Epimers are diastereomers that differ in conguration at only one of the severalstereogenic centers. Imagine taking any one of the many stereogenic centers in everninomi-cin (shown in the next Connections highlight) and changing the stereochemistry at only thatone stereogenic center. This creates an epimer of the original structure. Another example isthe difference between the - and -anomers of glucose, which are epimeric forms of thesugar (look ahead to Figure 6.18 for denitions of - and -anomers).3036.1 STER EOGENICITY AN D STEREOISOMER ISMConnectionsTotal Synthesis of an Antibiotic with these techniques have e is the total synthesis of ever-a Staggering Number of Stereocenters ninomicin 13,384–1. pound contains 13 ringsand 35 stereocenters (3.4 1010possible stereoisomers).Synthetic chemists are continually in search of new meth-Although many of the stereocenters were derived fromods to control the stereochemical e of syntheticthe ‘‘chiral pool’’(see Section 6.8.3), several stereocenterstransformations. Although the exact methods used areassociated with the ring connections and ring-fusionsbest described in textbooks with a focus upon asymmetricwere set with reactions that proceed with varying degreessynthesis, it is worth mentioning here how sophisticatedof stereoselectivity and specicity.the eld is ing. By analyzing how the topicity rela-tionships within reactants will inuence enantiomeric and Nicolaou, K. C., Mitchell, H. J., Suzuki, H., Rodriguez, R. M., Baudoin,disastereomeric selectivities, a multitude of reactions with O., and Fylaktakidou, C. ‘‘Total Synthesis or Everninomicin 13,384–1—Part1: Synthesis of A1B(A)C Fragment.’’ Angew. Chem. Int. Ed. Eng., 38, 3334–good stereochemical control have been developed. One), and munications.particular example that highlights just how far advancedOMeOMeOMe OH HO OHMeHOOHOMeOMeO OOHO MeMeClClOO OOMe MeMeMeMeOHOO OMeOHHOEverninomicin 13,384–1NO2OOOHOOOOOO6.1.2 Stereochemical DescriptorsAll anic chemistry texts provide a detailed presentation of the variousrules for assigning descriptors to stereocenters. Here we provide a brief review of the termi-nology to remind the student of the basics.Many of the descriptors for stereogenic units begin with assigning priorities to theattached ligands. Higher atomic number gets higher priority. If two atoms pari-son are isotopes, the one with higher mass is assigned the higher priority. Ties are settledby moving out from the stereocenter until a distinction is made. In other words, when twoattached atoms are the same, one examines the next atoms in the group, only looking for awinner by examining individual atomic numbers (do not add atomic numbers of severalatoms).Multiple bonds are treated that is, C O is treated as a C that is sin-gly bonded to two oxygens with one oxygen bound to a C. For example, the priorities shownbelow for the substituted alkene are obtained, giving an E-stereochemistry.OAn E-alkeneHigher PriorityOCH2CH3Lower PriorityOConsidered Considered asCR RH OOCBrHighest priorityLowest priorityCH3ClClCH3H3CHHigher priorityLower priorityLower priorityHigher priorityOOF304 CHAPTER 6: STEREOCHEM ISTRYHHOTurnmoleculeoverOH1122 33OHH OH(S)-2-Butanol (R)-2-ButanolOHigherpriorityLowerpriorityHigherpriority(Z )-3-Chloromethyl-3-penten-2-lR,S SystemFor tetracoordinate carbon and related structures we use the Cahn–Ingold–Prelog sys-tem. The highest priority group is given number 1, whereas the lowest priority group isgiven number 4. Sight down the bond from the stereocenter to the ligand of lowest prioritybehind. If movingfrom the highest (#1),to the second (#2),to the third (#3) priorityligand in-volves a clockwise direction, the center is termed R. A counterclockwise direction implies S.E,Z SystemFor olens and related structures we use the same priority rules, but we divide the dou-ble bond in half pare the two sides. For each carbon of an olen, assign one ligandhigh priority and one low priority according to the rules above. If the two high priority li-gands lie on the same side of the double bond, the system is Z (zusammen); if they are on op-posite sides, the system is E (entgegen). If an H atom is on each carbon of the double bond,however, we can also use the traditional ‘‘cis’’ and ‘‘trans’’ descriptors.d and lThe descriptors d and l represent an older system for distinguishing enantiomers,relating the sense of chirality of any molecule to that of d- and l-glyceraldehyde. d- andl-glyceraldehyde are shown below in Fischer projection form. In a Fischer projection, thehorizontal lines represent ing out of the plane of the paper, while the vertical linesrepresent bonds projecting behind the plane of the paper. You may want to review an intro-ductory text if you are unfamiliar with Fischer projections. The isomer of glyceraldehydethat rotates plane polarized light to the right (d) was labelled d, while the isomer that rotatesplane polarized light to the left (l) was labelled l.To name plex carbohydrates or amino acids, one draws a similar Fischer pro-jection where the CH2OH or R is on the bottom and the carbonyl group (aldehyde, ketone, orcarboxylic acid) is on the top. The d descriptor is used when the OH or NH2 on the penulti-mate (second from the bottom) carbon points to the right, as in d-glyceraldehyde, and l isused when the OH or NH2 points to the left. See the following examples.HO HH OHH OHCH2OHD-ArabinoseCHOOHO HH OHH OHCH2OHD–FructoseCH2OHH OHHO HH OHHO HCH2OHL-IdoseH NH2CH2PHD-PhenylalanineCO2HH OHCH2OHCHOH2N HCH2OHL-SerineCO2HCHOL-GlyceraldehydeOH =HCH2OHD-GlyceraldehydeCHOHO HCH2OHCHOH =HOCH2OHCHOThe d and l nomenclature system is fundamentally different than the R/S or E/Z sys-tems. The d and l descriptors derive from only one stereogenic center in the molecule andare used to name the entire molecule. The name of the sugar denes the stereochemistry ofall the other stereogenic centers. Each sugar has a different arrangement of the enters along the carbon backbone. In contrast, normally a separate R/S or E/Z descriptoris used to name each individual stereogenic unit in a molecule. The d/l nomenclature is acarry over from very early carbohydrate chemistry. The terms are now reserved primarilyfor sugars and amino acids. Thus, it monly stated that all natural amino acids are l,while natural sugars are d.3056.1 STER EOGENICITY AN D STEREOISOMER ISMErythro and ThreoAnother set of terms that derive from the stereochemistry of harides are erythro andthreo. The sugars shown below are d-erythrose and d-threose, which are the basis of a no-menclature system pounds with two stereogenic centers. If the two stereogenic cen-ters have two groups mon, we can assign the terms erythro and threo. To he use of the erythro and threo descriptors, draw pound in a Fischer projection withthe distinguishing groups on the top and bottom. If the groups that are the same are both onthe right or left side, pou if they are on opposite sides, -pound is called threo. See the examples given below. Note that these structures have enanti-omers, and hence require R and S descriptors to distinguish the specic enantiomer. Theerythro/threo system distinguishes diastereomers.H2N HH NH2PhThreoCO2HH NH2H NH2PhErythroCO2HHO HH OHCH2OHD-ThreoseCHOH OHH OHCH2OHD-ErythroseCHOBr HBr Ht-BuErythroCH3Br HH Brt-BuThreoCH3Helical Descriptors—M and PMany chiral molecules lack a conventional center that can be described by the R/S orE/Z nomenclature system. Typically these molecules can be viewed as helical, and mayhave propeller, or screw-shaped structures. To assign a descriptor to the sense of twist ofsuch structures, we sight down an axis that can be associated with the helix, and considerseparately the ‘‘near’’ and ‘‘far’’ substituents, with the near groups taking priority. We thendetermine the highest priority near group and the highest priority far group. Sighting downthe axis, if moving from the near group of highest priority to the corresponding far group re-quires a clockwise rotation, the helix is a right-handed helix and is described as P (or plus). Acounterclockwise rotation implies a left-handed helix and is designated as M (or minus). Asin all issues related to helicity, it does not matter what direction we sight down the axis, be-cause we will arrive at the same descriptor. Three examples of molecules with M/P descrip-tors are shown below.CH3CH3NO2O2NH3CH3CH SightClHC H3C HCCH3HHCHClCounterclockwiseMSightO2N CH3NO2CH3ClockwisePSightH CH3CH3HClockwisePAs another example, consider triphenylborane (Eq. 6.1, where a, b, and c are just labelsof hydrogens so that you can keep track of the rotations shown). Triphenylborane cannot befully planar because of steric crowding, and so it adopts a conformation with all three ringstwisted in the same direction, making a right- or left-handed propeller. The M or P descrip-306 CHAPTER 6: STEREOCHEM ISTRYtors are most easily assigned by making an analogy to mon screw or bolt. Commonscrews or bolts are right-handed (‘‘reverse thread’’ screws and bolts are left-handed). If thesense of twist is the same as a screw or bolt, it is assigned the P descriptor (check the P and Mdescriptors for yourself in Eq. 6.1).abcBaBcBbP M(Eq. 6.1)Rotation about the C–B bonds of triphenylborane is relatively facile, and the motionsof the rings are correlated in the sense shown (Eq. 6.1). In Eq. 6.1 the arrows denote thedirection of bond rotation, not the helical direction. Two rings rotate through a perpen-dicular conformation while one moves in the opposite way. This ‘‘two-ring ip’’ reverseshelicity and, in a substituted case (now a, b, and c in Eq. 6.1 are substituents), creates a newdiastereomer.Ent and EpiBecause of the plexity of many natural products, short and simpledescriptors e mon use to relate various stereochemical relationships. Forexample, the enantiomer of a structure with many stereogenic centers has the prex ent-.Ent-everninomicin is a trivial name that can be given to the enantiomer of everninomicin.Similarly,dueto plexityof manynaturalproducts,the prex epi-e a convenient way to name structures where only one stereogenic center has under-gone a change in conguration. For example, any epimer of everninomicin can be called epi-everninomicin. Usually, a number precedes ‘‘epi-’’ to distinguish which center has changedconguration.Using Descriptors pare pounds that have the same sense of chirality at their individual stereogenic centersare called homochiral. Homochiral molecules are not identical—they just have the samesenseofchirality,muchlikeallpeople’sright handsaredistinctbutofthesamechirality.Asachemical example,the amino acids l-alanineand l-leucine are homochiral.Those moleculeswith a differing sense of chirality at their stereogenic centers are called heterochiral. Thesame sense of chirality can often, but not always, be analyzed by examining whether thedifferent kinds of stereochemical descriptors at the stereogenic centers are the same. Forexample, (R)-2-butanol and (R)-2-aminobutane are homochiral. Further, all the naturally oc-curring amino acids are l, so they are all homochiral (see the next Connections highlight).Homochiral has been used by some as a synonym for ‘‘enantiomerically pure’’. This isanother usage of a term that should be discouraged, as homochiral already had a clear anduseful denition, and using the same term to signify pletely different conceptscan only lead to confusion. A better term for designating an enantiomerically pure sample issimply enantiopure.6.1.3 Distinguishing EnantiomersEnantiomers are distinguishable if and only if they are placed in a chiral environment,and all methods to separate or characterize enantiomers are based on this principle. Sup-pose, for example, that we have a collection of right- and left-handed gloves, and we want toretrieve only the right-handed ones. Using a simple hook to reach into the pile cannot suc-ceed because a hook is achiral—it cannot distinguish handedness. A chiral object, however,like a right hand, can distinguish between the gloves just by trying them on.播放器加载中，请稍候...
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Modern Physical Organic Chemistry, - Chapter6 - Stereochemistry(Eric V Anslyn, Dennis A Dougherty) 297CHAPTER 6StereochemistryIntent and PurposeStereochemistry is the study of the static and dynamic aspects of the three-dimensionalshapes of molecules. It has long provided a foundation for understand...
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