Organic chemistry 8th edition (2017) part 3 Organic chemistry 8th edition (2017) part 3 Organic chemistry 8th edition (2017) part 3 Organic chemistry 8th edition (2017) part 3 Organic chemistry 8th edition (2017) part 3 Organic chemistry 8th edition (2017) part 3 Organic chemistry 8th edition (2017) part 3 Organic chemistry 8th edition (2017) part 3
916 Chapter 20: Dienes, Conjugated Systems, and Pericyclic Reactions ienes for this purpose are cyclopentadiene and 1,3-cyclohexadiene In fact, cyclod pentadiene is reactive both as a diene and as a dienophile, and upon standing at room temperature, it forms a Diels-Alder self-adduct known by the common name dicyclopentadiene When dicyclopentadiene is heated to 170°C, a reverse Diels-Alder reaction takes place and cyclopentadiene is reformed H H Dicyclopentadiene The terms endo and exo are used for bicyclic Diels-Alder adducts to describe the orientation of substituents of the dienophile in relation to the two-carbon diene-derived bridge Exo (Greek, outside) substituents are on the opposite side from the dienederived bridge; endo (Greek, within) substituents are on the same side exo endo For Diels-Alder reactions under kinetic control, the endo orientation of the dienophile is favored (Figure 20.9) Treatment of cyclopentadiene with methyl propenoate (methyl acrylate) gives the endo adduct exclusively The exo adduct is not formed Diels-Alder reactions are not always so stereoselective Cyclopentadiene Methyl propenoate D. The Configuration of the Dienophile Is Retained The reaction is completely stereospecific at the dienophile If the dienophile is a cis isomer, then the substituents cis to each other in the dienophile are cis in the DielsAlder adduct Conversely, if the dienophile is a trans isomer, substituents that are trans in the dienophile are trans in the adduct Dimethyl cis-2-butenedioate cis Dimethyl cis -4-cyclohexene1,2-dicarboxylate Dimethyl trans-2-butenedioate trans Dimethyl trans -4-cyclohexene1,2-dicarboxylate Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 20.5 The Diels-Alder Reaction 917 E. The Configuration at the Diene Is Retained The reaction is also completely stereospecific at the diene Groups on the and positions of the diene retain their relative orientation 1 A picture of the transition state will help clarify the reason for this Bonds being formed in the transition state are shown as dashed red lines; bonds being broken are shown as dashed blue lines The groups that are inside on the diene end up on the opposite side from the dienophile A O A D B C O O BC D O O O C C B A B D A D C D B A O O O C H D B H O A O O Example 20.9 Stereochemistry of the DielsAlder Reaction Complete the following Diels-Alder reaction, showing the stereochemistry of the product Solution Reaction of cyclopentadiene with this dienophile forms a disubstituted bicyclic product The two ester groups are cis in the dienophile, and given the stereoselectivity of the Diels-Alder reaction, they are cis and endo in the product (Continued) Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 918 Chapter 20: Dienes, Conjugated Systems, and Pericyclic Reactions H COOCH3 H COOCH3 COOCH3 COOCH3 Problem 20.9 What diene and dienophile might you use to prepare the following racemic Diels-Alder adduct? Figure 20.9 Mechanism of the Diels-Alder reaction The diene and dienophile approach each other in parallel planes, one above the other, with the substituents on the dienophile endo to the diene There is overlap of the p orbitals of each molecule and syn addition of each molecule to the other As (1) new s bonds form in the transition state, (2) the !CH2! on the diene rotates upward and (3) the hydrogen atom of the dienophile becomes exo and the ester group becomes endo O C H H3CO O C H H3CO H C O OCH3 Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 20.5 The Diels-Alder Reaction 919 F. Exploiting the Stereochemistry of the Diels-Alder Reaction As we have mentioned repeatedly throughout the text, the synthesis of chiral products from achiral starting materials in an achiral environment invariably leads to a racemic mixture of products Nature achieves the synthesis of single enantiomers by using enzymes that create a chiral environment in which reaction takes place Enzymes, in fact, show such high enantiomeric and diastereomeric selectivity that the result of an enzyme-catalyzed reaction is generally only a single one of all possible stereoisomers Chemists have developed chiral catalysts that produce chiral products However, these catalysts are often far less stereoselective than nature’s enzyme catalysts, although great progress has been made in this field in recent years How then chemists achieve the synthesis of single enantiomers uncontaminated by their mirror images? One strategy they use is resolution (Section 3.9) to separate enantiomers and recover each in pure form The most common methods for resolution depend on (1) the different physical properties of diastereomeric salts, (2) the use of enzymes as resolving agents, and (3) chromatography on a chiral substrate While resolution is effective in preparing pure enantiomers, half of all product prepared to the point of resolution, namely the unwanted enantiomer, is lost in the process Thus, this strategy for the preparation of single enantiomers wastes starting materials and reagents We illustrate an alternative strategy, namely asymmetric induction, by E J Corey’s preparation of a key intermediate in his synthesis of prostaglandins In asymmetric induction, the reactive functional group of an achiral molecule is placed in a chiral environment by reacting it with a chiral auxiliary The strategy is that the chiral auxiliary then exerts control over the stereoselectivity of the desired reaction The chiral auxiliary chosen by Corey was 8-phenylmenthol This molecule has three chiral centers and can exist as a mixture of 23 possible stereoisomers It was prepared in enantiomerically pure form from naturally occurring, enantiomerically pure menthol Menthol 8-Phenylmenthol The initial step in Corey’s prostaglandin synthesis was a Diels-Alder reaction between a substituted cyclopentadiene and the double bond of an acrylate ester By binding the achiral acrylate reactant to enantiomerically pure 8-phenylmenthol, Corey placed the carbon-carbon double bond of the dienophile in a chiral environment The result was that the diene approached the carbon-carbon double bond of the acrylate preferentially from one direction A remarkable feature of this reaction is that it creates three chiral centers Two of the chiral centers, namely those at the two ring junctions, are established by the Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 920 Chapter 20: Dienes, Conjugated Systems, and Pericyclic Reactions Diels-Alder reaction The third, namely the endo position of the ester group, is also established by the Diels-Alder reaction Without the chiral auxiliary 8-phenylmenthyl group, two of the eight possible stereoisomers would be produced, namely the pair of enantiomers shown Although both enantiomers of the bicyclic products were formed in Corey’s scheme, they were formed in the ratio of 97:3 and the desired enantiomer could be separated in pure form In subsequent steps, the 8-phenylmenthyl ester was hydrolyzed and the pure enantiomer was converted to the so-called Corey lactone and then to enantiomerically pure prostaglandin F2a G. A Word of Caution About Electron Pushing Earlier we used curved arrows to show the flow of electrons that takes place in the process of bond breaking and bond forming in the Diels-Alder reaction As discussed, these reactions involve a four-carbon diene and a two-carbon d ienophile and are termed [4 2] cycloadditions We can write similar electron-pushing mechanisms for the dimerization of ethylene by a [2 2] cycloaddition to form cyclobutane and for the dimerization of butadiene by a [4 4] cycloaddition to form 1,5-cyclooctadiene Cyclobutane 1,5-Cyclooctadiene Although [2 2] and [4 4] cycloadditions bear a formal relationship to the DielsAlder reaction, neither, in fact, takes place under the thermal conditions required for Diels-Alder reactions (see Section 20.4) because they are forbidden as determined by the frontier molecular orbital analysis 20.6 Sigmatropic Shifts Sigmatropic shift A reaction in which a s bond migrates across the face of one or more p bonds The second class of pericyclic reactions that we examine is that of sigmatropic shifts These reactions consist of the movement of a s bond across the face of one or more p bonds Although many examples of these reactions are known, we are only going to analyze what is known as a [3,3]-shift The numbering system for the nomenclature of the shift derives from assigning the number to the ends of the s bond that is shifting and then naming the reaction to denote the number of atoms to which the s bond migrates There are two common versions of this reaction, known as the Claisen and Cope rearrangements Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 20.6 Sigmatropic Shifts 921 To derive the frontier molecular orbital analysis for any [3,3]-shift, we’ll use 1,5-hexatriene as the model, just as we used butadiene and ethylene as models for the frontier molecular orbital analysis of all Diels-Alder reactions As always, in a frontier molecular orbital analysis, we first identify a proposed geometry for the reaction Let’s propose a chairlike transition state in which the carbons on the ends of the chain react from the top of one p bond and the bottom of the other 1 The next step of a frontier molecular orbital analysis involves identifying a HOMO and a LUMO and checking to see if the HOMO and LUMO can interact with matched phasings (Figure 20.10) In this case, we assign the s bond that is migrating to be the HOMO; it is thus drawn as the overlap of two sp3 hybrid orbitals (see Figure 1.18) The LUMO is assigned to be a molecular orbital that is a mixture of the two alkenes when their ends are in close proximity [Figure 20.10(a)] and in a trajectory to react in a manner consistent with a chairlike geometry of the transition state The molecular orbitals that result from the mixture of two separate alkenes are analogous to those found in butadiene Hence, the LUMO for the [3,3]-shift is phased identical to the LUMO of butadiene [compare the LUMO indicated in Figure 20.10(a) to orbital in Figure 20.2] However, there is one important difference In orbital of Figure 20.2, the two central p orbitals are in phase when parallel But in our analysis of the Cope reaction, the top of one of the central p orbitals is placed in phase with the bottom of the other because this is the interaction geometry we are analyzing (a) (b) Figure 20.10 (a) Proper phasing of orbitals for the frontier molecular orbital analysis of a [3,3]-sigmatropic shift; note the phasing interaction between the terminal carbons when the top of one p bond interacts with the bottom of the other in-phase (b) Reorientation showing how the chair conformation leads to in-phase interactions throughout the [3,3]-shift p We can now check to see if the HOMO and LUMO phases match In Figure 20.10(b), we redraw the chair with the s bond vertically for clarity The arrows show matched phasing that leads to a s bond and two p bonds in the product that are all in phase and bonding Hence, the reaction is allowed In summary, the frontier molecular orbital approach finds that there is an allowed geometry for reaction with the ends of the p bonds of a 1,5-diene as in a Cope rearrangement (or analogously a Claisen rearrangement) with a chairlike transition state Interestingly, a boatlike transition state is also allowed, although it is conformationally less stable (see Problem 20.48) Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 922 Chapter 20: Dienes, Conjugated Systems, and Pericyclic Reactions A. The Claisen Rearrangement One example of the Claisen rearrangement transforms allyl phenyl ethers to o-allylphenols Heating allyl phenyl ether, for example, the simplest member of this class of compounds, at 200–250°C results in a Claisen rearrangement to form o-allylphenol In this rearrangement, an allyl group migrates from a phenolic oxygen to a carbon atom ortho to it Carbon-14 labeling, here shown in color, has demonstrated that during a Claisen rearrangement, carbon of the allyl group becomes bonded to the ring carbon ortho to the phenolic oxygen Allyl phenyl ether 2-Allylphenol The mechanism of a Claisen rearrangement involves a concerted redistribution of six electrons in a cyclic transition state, as described above The product of this rearrangement is a substituted cyclohexadienone, which undergoes keto-enol tautomerism to reform the aromatic ring A new carbon-carbon bond is formed in the process Mechanism 20.2 The Claisen Rearrangement Step 1: Sigmatropic shift. Redistribution of six electrons in a cyclic transition state gives a cyclohexadienone intermediate Dashed red lines indicate bonds being formed in the transition state, and dashed blue lines indicate bonds being broken Step 2: Keto-enol tautomerism. Keto-enol tautomerism restores the aromatic character of the ring ‡ Allyl phenyl ether 2-Allylphenol Thus, we see that the transition state for the Claisen rearrangement bears a close resemblance to that for the Diels-Alder reaction Both involve a concerted redistribution of six electrons in a cyclic transition state Example 20.10 The Claisen Rearrangement Predict the product of Claisen rearrangement of trans-2-butenyl phenyl ether trans-2-Butenyl phenyl ether Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 20.6 Sigmatropic Shifts 923 Solution In the six-membered transition state for this rearrangement, carbon of the allyl group becomes bonded to the ortho position of the ring ‡ Problem 20.10 Show how to synthesize allyl phenyl ether and 2-butenyl phenyl ether from phenol and appropriate alkenyl halides B. The Cope Rearrangement The Cope rearrangement of 1,5-dienes also takes place via a cyclic six-electron transition state In this example, the product is an equilibrium mixture of isomeric dienes The favored product is the diene on the right, which contains the more highly substituted double bonds Mechanism 20.3 The Cope Rearrangement Pericyclic reaction. Redistribution of six electrons in a cyclic transition state converts a 1,5-diene to an isomeric 1,5-diene ‡ 3,3-Dimethyl1,5-hexadiene 6-Methyl-1,5heptadiene Example 20.11 The Cope Rearrangement Propose a mechanism for the following Cope rearrangement (Continued) Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 924 Chapter 20: Dienes, Conjugated Systems, and Pericyclic Reactions Solution Redistribution of six electrons in a cyclic transition state gives the observed product ‡ Problem 20.11 Propose a mechanism for the following Cope rearrangement C. Stereochemistry of the Cope Rearrangement As discussed during the previous frontier molecular orbital theory analysis of [3,3]-sigmatropic shifts, a chairlike transition state is allowed for these reactions As you will show in Problem 20.48, a boatlike transition state is also allowed by frontier molecular orbital theory However, chair conformations are more favorable than boat conformations for six-membered cyclic rings (look back at Section 2.5A) This preference influences the stereochemistry of these shifts, as we now show with an example Example 20.12 Stereochemistry, the Cope Rearrangement Upon heating the meso version of 3,4-dimethyl-1,5-hexadiene, three products with differing alkene stereochemistry from the Cope rearrangement are possible, but only two are found, with one being highly preferred Show all three possible products and predict the preference in the distribution Solution The products and preference for the cis-trans alkenes can be explained by redrawing the reactant in chair- and boatlike conformations These drawings reveal that the preferred product arises from a chairlike transition state cis trans cis trans Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 Study Guide 925 Watch a video explanation Problem 20.12 Upon heating a racemic mixture of d,l-3,4-dimethyl-1,5-hexadiene, three products are possible, and all three are observed The ratios are 90, 9, and nearly percent Predict which percentages correspond to which products and explain the ratio by showing the chair and boat conformations that lead to the products trans cis cis trans Study Guide 20.1 Stability of Conjugated Dienes ●● A conjugated diene is one in which the double bonds are separated by only one single bond so that the 2p orbitals of the adjacent p bonds overlap – An unconjugated diene is one in which the double bonds are separated by two or more single bonds – A cumulated diene is one in which the two double bonds share an sp hybridized carbon In a cumulated diene, the 2p orbitals of the p bonds not overlap; so they are not conjugated ●● The two conjugated double bonds in conjugated dienes are 14.5–17 kJ (3.5–4.1 kcal)/mol more stable than isomeric nonconjugated dienes, an observation that e xtends to all conjugated double bonds, not just dienes – The increased stability of conjugated double bonds results from delocalization of the four p electrons over the set of four parallel 2p orbitals – According to molecular orbital theory, two conjugated double bonds are derived from four p molecular orbitals because the four parallel 2p orbitals overlap in space, even the 2p orbitals on either side of the single bond between the conjugated double bonds – The lowest two p molecular orbitals have zero and one node, respectively, are bonding orbitals, and are filled with two electrons each – Each of these lowest two filled p molecular orbitals is at an energy that is lower than isolated p bonds, accounting for the “extra” stability of conjugated p systems – The lowest filled p molecular orbital has large lobes extending over all four atoms, illustrating the delocalization of electron density in conjugated p systems – In order for maximal overlap to occur, the 2p orbitals must be parallel; so the sp2 atoms of the conjugated systems must be coplanar P 20.1, 20.2, 20.6, 20.14, 20.15 Figure 20.2 Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 Index Toremifene, 993–994 Torsional strain, 87 Tosyl chloride (TsCl), 452, 763, 786 Tranquilizer, 813 Trans, 100, 212 Trans-alkene, 314, 322 trans dienophile, 916 Trans fats, 1192 Trans fatty acids, 276–277 Transaminase, 682 Transesterification, 787, 788, 805 Transfer (tRNA), 1248t, 1249–1250 Transition metal catalysis, 737 Transition-metal nucleophilic-carbene catalysts, 1113, 1115 Transition state, 184, 185, 243 Transmetallation, 1107 Tree diagrams, 579, 580 Trehalose, 1165 Triacontyl palmitate, 1172 Triacylglycerols, 1171 See also Triglycerides Trialkenylborane, 308 Trialkylboranes, 267 2,4,6-Tribromophenol, 955 Tricarboxylic acid (TCA) cycle, 154 Trichlor, 332 Trichloroacetic acid, 732 1,3,5-Trichlorobenzene, 1066 1,1,1-Trichloroethane, 332 Trichloroethylene, 332 Trichloromethane, 332 (Z)-9-Tricosene, 637 tridec-, 77t Tridecane, 74t (E)-5-Tridecene, 637 Trienes, 216 Triethanolamine, 527 Triethylamine acid strength, 1046t acidity/basicity, 1082 boiling point, 1045t melting point, 1045t nomenclature, 1040 reaction with alcohols, 786 solubility, 1045t structural formula, 1045t structure, 1046t tertiary amine, 1082 Triethylammonium chloride, 451, 1041 Triethylborane, 265 Triethylsilyl chloride (TESCl), 504 Triethylsilyl (TES) group, 504 Triflates, 1099 4,4,4-Trifluoro-1-butanol, 191 3,3,3-Trifluoro-1-propanol, 191 2,2,2-Trifluoroethanol, 190, 191 Trifluoromethanesulfonates, 1099 Trifluoromethanesulfonyl chloride, 1099 Trifluoromethylbenzene, 1029 Trifluralin B, 1026 Triglycerides, 220, 1171–1174, 1191–1192 2,3,4-Trihydroxybutanal, 137, 138 Triiodoaromatics, 1091 l-Triiodothyronine, 1202 Triisopropylsilyl chloride (TIPSCl), 504 Triisopropylsilyl (TIPS) group, 504 3,7,11-Trimethyl-2,6,10-dodecatrien1-ol, A-17 (2E,6E)-3,7,11-Trimethyl-2,6,10dodecatrien-1-ol, A-17 Trimethylamine, 21, 1038, 1045t, 1046t 1,2,4-Trimethylcyclohexane, 98 3,7,11-Trimethyldodecan-1-ol, A-17 2,2,4-Trimethylpentane, 82, 114, 615 Trimethylphosphine, 39 Trimethylphosphite, 668 Trimethylsilyl chloride (TMSCl), 504 Trimethylsilyl (TMS) group, 504 2,4,6-Trinitrophenol, 959, 960 Triose, 1135 Tripeptide, 1208 Triphenylmethyl (trityl) ethers, 985 Triphenylphosphine, 666, 1100 Triphosphate ion, 764 Triphosphoric acid, 764 Trisaccharides, 1151 Trisubstituted carbon-carbon double bonds, 273 Triterpenes, 1184 Trityl ethers See Triphenylmethyl (trityl) ethers tRNA See Transfer (tRNA) Tropical oils, 1172 Tropylium cation, 622 Trp, 1201t See also Tryptophan Trypsin, 1212 Tryptophan, 1201t, 1203t Ts See Toluenesulfonyl group (Ts) TsCl See Tosyl chloride (TsCl) Tub conformation, 948 Tumeric flower, 894 Turnover, 1096 Turpentine, 220 Twist-boat conformation, 93, 93 Twisting, 540 Type A blood, 1154 Type B blood, 1154 Type O blood, 1154 Tyr, 1201t See also Tyrosine Tyrosine, 1201t, 1203t U U See Uracil (U) Ullmann coupling, 1036 Ultraviolet-visible radiation, 904 Ultraviolet-visible spectroscopy, 537t, 904–908 absorbance, 905 Beer-Lambert law, 905, 906–907 percent transmittance, 905 I-43 pSp* transition, 907, 908t review/study guide, 926–927 ultraviolet-visible radiation, 904 Unbranched alkyl substituents, 79 Unconjugated diene, 894, 895 Unconjugated double bonds, 895 undec-, 77t Undecane, 74t Undecanenitrile, 784, 785 Undecanoic acid, 784, 785 Unimolecular reaction, 379 Unoprostone, 1195 Unpaired electron density, 70 Unpleasant odors, 731 Unsaturated alcohols, 440 Unsaturated fatty acids, 1171t, 1173t, 1174 Unsaturated hydrocarbons, 73, 206 Unsaturated a,b-unsaturated carbonyl, 831 Unstabilized ylides, 668 Unstable structures, “Up is up and down is down,” 100 Upfield, 565, 565 Upholstery, 1273 Uracil (U), 1144, 1239 Urea, 790 Urea-formaldehyde thermosets, 1275 Urethane, 819, 1272 Uridine, 1240 Urografin, 1091 Uronic acid, 1146–1147 UV-visible radiation, 904 UV-visible spectroscopy See Ultraviolet-visible spectroscopy V Vaginal yeast infections, 1030 Val, 1201t See also Valine Valence bond theory (VB theory), 34–38, 653 Valence electrons, Valence shell, 6, 69 Valence-shell electron-pair repulsion (VSEPR), 24–26 defined, 24 predicted molecular shape, 26t resonance, 55 Valeric acid, 728t Valine, 1201t, 1203t Valium, 1030 Valnoctamide, 887 Valproic acid, 879 van der Waals, J D., 333 van der Waals forces, 333 van der Waals radius, 333, 333t van der Waals strain, 89 Vancomycin, 1129 Vancomycin aglycon, 1129 Vanilla pompona, 957 Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 I-44 Index Vanillic acid, 688 Vanillin, 688, 957, 1165 Variants of acetoacetic ester synthesis, 848 VB theory See Valence bond theory (VB theory) Venlafaxine, 1031–1032 Verapamil, 886 Very-high-molecular-weight alkanes, 118 Viagra, 1090 Vibrational infrared region, 538 Vicinal coupling, 574 Vicinal diol, 270 Vicinal hydrogens, 574 Vinyl, 212 Vinyl acetate, 588 Vinyl chloride, 307, 331, 1266, 1276t See also Poly(vinyl chloride) (PVC) Vinyl ethers, 546 Vinyl triflates, 1110 Vinylacetylene, 299 Vinylcyclopentane, 212 Vinylic carbocation, 306 Vinylic halide, 331 Vinylic hydrogen, 570–572 Viscose rayon thread, 1156 Visible light color-wavelength correlation, 906 Visual cycle, 1188, 1189 Visual purple, 680 Vitamin A, 217, 220, 883, 1188 Vitamin A acetate, 718 Vitamin A aldehyde, 680 Vitamin B6, 682–684 Vitamin C, 1141 Vitamin D, 1188–1189 Vitamin D3, 1188 Vitamin E, 355, 1189–1190 Vitamin K deficiency, 1190–1191 Vitamin K2, 965, 965 Vitamin K1 base, 1190, 1191 von Euler, Ulf, 1178 VSEPR See Valence-shell electron-pair repulsion (VSEPR) W Wacker process, 737 Wagging, 540 Warburganal, 933 Warfarin, 766, 883 Water, A-2 carboxylic acid derivatives See Hydrolysis electrostatic potential map, 28 Lewis structure, 13t, 25 orbital overlap picture, 36 pKa, 445t protic solvent, 389t shape, 25 Watson, James D., 1243, 1245, 1246 Watson-Crick model, 1243, 1244 Wave equation, 29 Wave function, 30 Wave mechanics, 30 Wavelength, 535, 536t Wavenumbers, 538, 541 Weak nucleophile, 393 Weight average molecular weight (Mw), 1267 Wellbutrin, 1030 West Indian vanilla, 957 Western pine beetle, 884 Whinfield, John Rex, 1271 Wilkins, Maurice, 1243, 1244 Williamson ether synthesis, 496–497, 962 Willow bark, 730 Wine making, 694 Wittig, Georg, 666 Wittig carbanion, 668 Wittig reaction, 666–669 examples (reactions of Wittig reagents), 669 Horner-Emmons-Wadsworth modification, 668, 704 importance, 704 key reactions, 704 reaction mechanism, 667 review/study guide, 703–704 stages, 666 steric hindrance, 704 Wolff, L., 697 Wolff-Kishner reduction, 697–698, 709 Woodward, R B., 909 X X-ray diffraction patterns, 1244 m-Xylene, 955 p-Xylene, 968, 1272 Xylitol, 1145, 1146 Xylocaine, 765 Y Ylide, 666–669 -yn-, 81 Yomogi alcohol, 488 Z Z, 213 Z— protecting group See Benzyloxycarbonyl (Z—) protecting group Zaitsev elimination, 401, 1069 Zaitsev’s rule, 401, 480, 1069 Zero-carbon bridge, 84 Zidovudine (AZT), 1244–1245 Ziegler, Karl, 1279 Ziegler-Natta chain-growth polymerization, 1279–1282, 1296 Zimmerman, Howard, 909 Zinc-10-undecenoate, 751 Zocor, 839, 840 Zoloft, 491 Zwitterion, 1054, 1200, 1205, 1206 Zyban, 1030 Zyrtec, 532 Zyvox, 821–822 Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 Appendix 10 Organic Chemistry Reaction Roadmaps Reaction Roadmap End of chapter problems marked with this icon use reaction roadmaps An organic chemistry reaction roadmap is a graphical representation of the many organic reactions in the context of the important functional groups The functional groups of an organic chemistry reaction roadmap are analogous to cities on a real roadmap, and the reactions are the roads between those cities Arrows are used to represent routes that are known between functional groups, and the reagents required to bring about each reaction are written next to the corresponding arrow For the reaction roadmaps that follow, the arrows and reagents are color coded to denote the chapter in which the reaction is first described Multistep synthesis questions are often the most challenging for organic chemistry students even though synthesis is at the core of organic chemistry as a discipline The problem comes down to keeping track of the different reactions encountered throughout the course in such a way that they can be recalled in the context of transforming simpler molecules into more complex molecules The power of the organic chemistry reaction roadmap is that it visualizes the reactions introduced in different chapters in a context that emphasizes how these reactions can be used in specific sequences to interconvert key functional groups in multistep synthesis problems Often it is not possible to change one functional group into another with a single reaction The roadmap helps you deduce a pathway that is possible when several different reactions are required For example, you will notice that you cannot create an alkyne directly from an alkane However, by looking at the roadmap for Chapters 6–11, you observe that it is possible to convert an alkane into a haloalkane (Br2 and hn), followed by an E2 elimination (strong base) to give an alkene The alkene can then be reacted with X2 to give a vicinal dihaloalkane, which is then reacted with NaNH2 in NH3 to give the alkyne Of course, you always need to keep track of both regiochemistry (i.e., Markovnikov addition to an alkene, replacement of an H atom at the most substituted carbon, etc.) and stereochemistry (syn vs anti, inversion of a chiral center, etc.) in order to predict accurately the products of a reaction sequence In order to avoid having too much information on a single page, several different roadmaps have been created In particular, there is a roadmap for Chapters 6–11, Chapters 15–18, Chapter 19, and Chapters 20–23 Although these roadmaps are intended to be a useful reference, you will benefit from making and using your own roadmaps See the end of chapter problems throughout this book The authors’ students have been making and using roadmaps for almost two decades now, and these roadmaps are universally credited with making organic chemistry lecture courses a much richer learning experience Reactions that make carbon-carbon bonds are particularly useful for organic synthesis because it allows the construction of larger molecules from smaller fragments All of the many carbon-carbon bond-forming reactions are indicated on the following roadmaps as reagents with solid backgrounds For the two reactions involving the cleavage of carbon-carbon bonds, the reagents are circled Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 ROADMAP FOR REACTIONS Chapter ROADMAP FOR REACTIONS Chapters Chapter vicinal tetrahaloalkanes geminal dihaloalkanes 2HX (A) Chapter Chapter Chapter 2X2 1) (sia)2BH, 2) H2O2, NaOH (C) 1) BH3, 2) H2O2, NaOH alkynes vicinal tetrahaloalkanes geminal dihaloalkanes Reactions that cleave carbon-carbon bonds are indicated by reagents that are circled aldehydes/ ketones 2X2 2HX (A) 1) (sia)2BH, 2) H2O2, NaOH (C) alkynes vicinal dihaloalkanes halohydrins 1) O3, 2) (CH3)2S 1) O3, 2) (CH3)2S 1) OsO4 (D), 2) NaHSO3 1) BH3, 2) H2O2, NaOH (C, D) 1) BH3, 2) H2O2, NaOH (C, D) 1) Hg(OAc)2, H2O, 2) NaBH4, (A) alcohols (A) 1) Hg(OAc)2, H2O, 2) NaBH4, (A) alcohols alkanes alkenes H2/Pd, Pt,or Ni (D) H3O+/H2O (A) 1) Hg(OAc)2, H2O, 2) NaBH4, (A) alcohols NBS (O) allylic halides HX (A) alkenes H2/Pd, Pt,or Ni (D) 2O HBr, peroxides (C) H2/Pd, Pt,or Ni (D) alkanes H3 1) BH3, 2) H2O2, NaOH (C, D) HX (A) alkanes H3O+/H2O (A) alkenes O+/H vicinal diols X2 (B) vicinal diols X2/H2O (B) X2 (B) 1) OsO4 (D), 2) NaHSO3 vicinal diols aldehydes/ ketones NaNH2 /NH3 H2 /Lindlar Cat (F) Na /NH3 (G) H2 /Pd, Pt, Ni NaC RC halohydrins X2/H2O (B) 1) OsO4 (D), 2) NaHSO3 CR (E) vicinal dihaloalkanes 1) O3, 2) (CH3)2S 1) BH3, 2) H2O2, NaOH H2SO4, HgSO4 (A) NaNH2 /NH3 H2 /Lindlar Cat (F) Na /NH3 (G) H2 /Pd, Pt, Ni CR (E) halohydrins Carbon-carbon bond forming reactions are indicated by reagents written with solid backgrounds and white lettering Reactions that cleave carbon-carbon bonds are indicated by reagents that are circled aldehydes/ ketones H2SO4, HgSO4 (A) NaC dihaloalkanes X2 (B) (P) (Q) Carbon-carbon bond forming reactions are indicated by reagents written with solid backgrounds and white lettering Chapter Reactions that cleave carbon-carbon bonds are indicated by reagents that are circled } HX (A) (M) (N) (O) X2/H2O (B) (L) Regiochemistry: Markovnikov addition to a π bond Stereochemistry: anti-addition Regiochemistry: non-Markovnikov addition to a π bond Stereochemistry: syn-addition Works well for methyl and 1° haloalkanes Stereochemistry: gives cis-alkenes as products Stereochemistry: gives trans-alkenes as products Reactivity of C–H bonds follows 3° > 2° > 1° Works for methyl, 1°, and 2° haloalkanes Works for 2° and 3° haloalkanes, may see rearrangements Works for all haloalkanes except methyl, although a bulky (non-nucleophilic) base must be used for 1° haloalkanes Regiochemistry: follows Zaitzev’s rules so the more substituted alkene predominates Stereochemistry: requirement for the X and H to be eliminated with anti-periplanar geometry PBr3 and SOX2 works for methyl, 1°, and 2° haloalkanes HX can give rearrangements For 1° alcohols PCC = pyridinium chlorochromate For 2° alcohols Regiochemistry: the product with the more substituted alkene predominates DMP = Dess-Martin periodinane Swern oxidation = 1) oxalyl chloride, vicinal DMSO; 2) tertiary amine Chapters Key: Key: (A) (B) (C) (D) (E) (F) (G) (H) ( I) (J) (K) ROADMAP FOR REACTIONS X2, hv or heat (H) haloalkanes haloalkanes haloalkanes (A) (B) (C) (D) (E) (F) (G) (H) (I) (J) (K) (L) (M) (N) (O) (P) (Q) Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 Regiochemistry: Markovnikov addition to a π bond Stereochemistry: anti-addition Regiochemistry: non-Markovnikov addition to a π bond Stereochemistry: syn-addition Works well for methyl and 1° haloalkanes Stereochemistry: gives cis-alkenes as products Stereochemistry: gives trans-alkenes as products Reactivity of C–H bonds follows 3° > 2° > 1° Works for methyl, 1°, and 2° haloalkanes Works for 2° and 3° haloalkanes, may see rearrangements Works for all haloalkanes except methyl, although a bulky (non-nucleophilic) base must be used for 1° haloalkanes Regiochemistry: follows Zaitzev’s rules so the more substituted alkene predominates Stereochemistry: requirement for the X and H to be eliminated with anti-periplanar geometry PBr3 and SOX2 works for methyl, 1°, and 2° haloalkanes HX can give rearrangements For 1° alcohols For 2° alcohols PCC = pyridinium chlorochromate Regiochemistry: the product with the more substituted alkene predominates DMP= Dess-Martin periodinane Swern oxidation = 1) oxalyl chloride, DMSO; 2) tertiary amine } Chapters 10 halohydrins alkanes nitriles thioethers DMP (P) H2CrO4 (N) H2CrO4 HX or PBr3 or SOCl2 (L) H2O, acid (J) NaOH (E) ROH (J) HI X2, hv or heat (H) ethers amines alkyl azides Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 nitriles thiols thioethers amines NaN3 (I ) NHR2 ( I ) NaSH ( I) carboxylic acids NaCN (I ) NaN3 ( I) haloalkanes NaNR2 (I ) NaSR (I ) NaSH ( I ) thiols ROH/acid (J) NaOR (K) allylic halides H2CrO4 HX or PBr3 or SOCl2 (L) H2O (J) NaOH (E) ROH (J) NaOR (E) NaOR (K) HX (A) ethers X2, hv or heat (H) NaCN (I) NaNR2 (I ) NaN3 (I ) alkyl azides NH3 1) LiAlH4 2) H2O alcohols 1) Hg(OAc)2, H2O, 2) NaBH4, (A) H3PO4 haloalkanes amines alkenes H2/Pd, Pt,or Ni (D) alkyl azides carboxylic acids TBAF t-BuMe3SiCl/pyridine alcohols 1) Hg(OAc)2, H2O, 2) NaBH4, (A) NBS (O) HBr, peroxides (C) H2O (J) NaOH (E) ROH (J) NaOR (E) allylic halides HIO4 H3O+/H2O (A) (A) H3PO4 ethers NaOR (K) HX (A) NaSR ( I ) thioethers X2 (B) X2/H2O (B) 1) BH3, 2) H2O2, NaOH (C, D) NBS (O) HBr, peroxides (C) NaSH ( I) NaCN (I ) alkenes H2/Pd, Pt,or Ni (D) epoxides m-CPBA HX (A) alkanes vicinal aminoalcohols H3O+/H2O vicinal diols 1) Cl2, H2O, 2) NaOH, H2O NaSR ( I ) alcohols haloalkanes thiols 1) OsO4 (D), 2) NaHSO3 HBr, peroxides (C) 1) Hg(OAc)2, H2O, 2) NaBH4, (A) X2, hv or heat (H) nitriles halohydrins vicinal diols X2 (B) X2/H2O (B) X2/H2O (B) X2 (B) H3O+/H2O (A) H3O+/H2O NBS (O) allylic halides vicinal dihaloalkanes 1) BH3, 2) H2O2, NaOH (C, D) 1) BH3, 2) H2O2, NaOH (C, D) aldehydes/ ketones 1) O3, 2) (CH3)2S 1) OsO4 (D), 2) NaHSO3 vicinal diols 1) BH3, 2) H2O2, NaOH H2SO4, HgSO4 (A) NaC vicinal dihaloalkanes alkynes 1) O3, 2) (CH3)2S 1) OsO4 (D), 2) NaHSO3 alkenes HIO4 H2 /Lindlar Cat (F) Na /NH3 (G) H2 /Pd, Pt, Ni NaC CR (E) NaC halohydrins CR (E) NaNH2 /NH3 H2 /Lindlar Cat (F) Na /NH3 (G) H2 /Pd, Pt, Ni CR (E) NaC CR (E) NaC vicinal dihaloalkanes H2/Pd, Pt,or Ni (D) aldehydes/ ketones H2SO4, HgSO4 (A) 1) O3, 2) (CH3)2S alkanes 1) BH3, 2) H2O2, NaOH NaNH2 /NH3 H2SO4, HgSO4 (A) alkynes 1) (sia)2BH, 2) H2O2, NaOH (C) NaNH2 /NH3 aldehydes/ ketones Chapter 11 2X2 2HX (A) Reactions that cleave carbon-carbon bonds are indicated by reagents that are circled Chapter 10 Swern oxidation (Q) 1) (sia)2BH, 2) H2O2, NaOH (C) H2 /Lindlar Cat (F) 2X2 2HX (A) Chapter vicinal tetrahaloalkanes geminal dihaloalkanes Na /NH3 (G) 1) BH3, 2) H2O2, NaOH Chapter 10 Chapter H2 /Pd, Pt, Ni 1) (sia)2BH, 2) H2O2, NaOH (C) alkynes vicinal tetrahaloalkanes geminal dihaloalkanes Reactions that cleave carbon-carbon bonds are indicated by reagents that are circled Chapter Chapter CR (E) 2X2 Chapter Carbon-carbon bond forming reactions are indicated by reagents written with solid backgrounds and white lettering Chapter NaC vicinal tetrahaloalkanes Chapter CR (E) Chapter Carbon-carbon bond forming reactions are indicated by reagents written with solid backgrounds and white lettering Reactions that cleave carbon-carbon bonds are indicated by reagents that are circled DMP (P) Chapter Chapter H2CrO4 (N) Chapter Carbon-carbon bond forming reactions are indicated by reagents written with solid backgrounds and white lettering Swern oxidation (Q) Chapter 2HX (A) Key: Key: Key: geminal dihaloalkanes ROADMAP FOR REACTIONS Chapters 10 11 PCC (M) ROADMAP FOR REACTIONS NaOR (E) Chapters PCC (M) ROADMAP FOR REACTIONS silyl ethers Chapter 15 ROADMAP FOR REACTIONS Chapters 15 16 ROADMAP FOR REACTIONS Carbon-carbon bond forming reactions reactio are indicated by reagents reagen written with solid backgrounds and white lettering backgr Carbon-carbon bond forming reactions are indicated by reagents written with solid backgrounds and white lettering -unsaturated esters acetals -haloketones -hydroxyalkynes Key: cyanohydrins Chapter 15 vinyl halides haloalkanes O Zn (Hg), HCl H3O+/H2O , 3) H3O+/H2O alcohols geminal dihalo cyclopropanes CHX3 (CH3)3COK cyclopropanes y p p CH2I2 Zn (Cu) vinyl halides R2CuLi haloalkanes alkenes alkanes RNH2 N2H4 , KOH imines amine, NaBH3CN aldehydes/ ketones R2NH ROH/H+ Pt, H2 alkenes R2CuLi 1) Mg, 2) 1) NaCN 2) H2O 1) RC CNa 2) H3O+/H2O 1) NaBH4 , 2) H3O+ CH2I2 Zn (Cu) OEt 1) RLi, 2) H3O+ cyclopropanes CH2C 1) RMgX, 2) H3O+ CHX3 (CH3)3COK (MeO)2P 2) Base Ph3P + geminal dihalo cyclopropanes O CR2– hemiacetals O 1) Br2, acid ROH/H+ H3O+/H2O Chapter 16 enamines amines 1) Mg, Mg 2) O Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 , 3) H3O+/H2O alcohols ROADMAP FOR REACTIONS Chapters 15 16 17 18 Carbon-carbon bond forming reactio are indicated by reactions reagen written with solid reagents backgr backgrounds and white lettering Carbon-carbon bond forming reactio reactions are indicated by reagen reagents written with solid backgr backgrounds and white lettering -unsaturated esters acetals -haloketones -hydroxyalkynes cyanohydrins Key: -unsaturated esters acetals Chapter 15 -haloketones -hydroxyalkynes Key: cyanohydrins Chapter 15 Chapter 16 1) Mg, 2) O , 3) H3O+/H2O Zn (Hg), HCl aldehydes/ ketones H3O+/H2O vinyl halides R2CuLi haloalkanes 1) Mg, 2) RNH2 alkenes 1) DIBAL, 2) H3O+ CH2I2 Zn (Cu) Pt, H2 cyclopropanes 1) NaBH4 , 2) H3O+ CHX3 (CH3)3COK 1) RLi, 2) H3O+ geminal dihalo cyclopropanes 1) Mg 2) CO2 3) H3O+/H2O 1) Mg 2) CO2 3) H3O+/H2O O , 3) H3O+/H2O alcohols H2O, acid or base ROH, acid carboxylic acids H2O ROH esters NHR2 ROH H2O esters SOCl2 SOCl2 acid chlorides CH2N2 ROH, acid enamines amines CH2N2 carboxylic acids imines 1) LiAlH4 , 2) H3O+/H2O 1) LiAlH4 , 2) H3O+/H2O alkanes N2H4 , KOH R2NH ROH/H+ CR2– RNH2 alcohols Chapter 18 1) 2RMgX, 2) H2O haloalkanes enamines amines OEt 1) RMgX, 2) H3O+ R2CuLi imines Pt, H2 vinyl halides alkenes 1) NaBH4 , 2) H3O+ CH2I2 Zn (Cu) 1) RLi, 2) H3O+ cyclopropanes 1) RMgX, 2) H3O+ CHX3 (CH3)3COK Ph3P + geminal dihalo cyclopropanes CH2C hemiacetals 1) R2CuLi, 2) H2O H3O+/H2O N2H4 , KOH amine, NaBH3CN aldehydes/ ketones R2NH ROH/H CR2– hemiacetals alkanes (MeO)2P 2) Base Chapter 17 1) NaCN 2) H2O 1) RC CNa 2) H3O+/H2O 1) LiAlH4 , 2) H3O+/H2O Zn (Hg), HCl + O Ph3P + OEt O 1) Br2, acid CH2C 1) NaCN 2) H2O ROH/H+ (MeO)2P 2) Base 1) RC CNa 2) H3O+/H2O H3O+/H2O O Chapter 17 Br2, acid O 1) ROH/H+ H3O+/H2O Chapter 16 amine, NaBH3CN Chapters 15 16 17 ROADMAP FOR REACTIONS acid chlorides RCO2H acid anhydrides NHR2 amides 1) LiAlH4 , 2) H3O+/H2O NHR2 H2O acid or base H2O acid or base Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 nitriles 1) LiAlH4 , 2) H3O+/H2O ROADMAP FOR REACTIONS Chapter 19 Carbon-carbon bond forming reactions are indicated by reagents written with solid backgrounds and white lettering ketones, aldehydes -Hydroxy carbonyls Aldol Reaction R3 NaOR/HOR H3O HO R4 R1 R2 -Unsaturated carbonyls + R2 R4 R1 O O -Alkylated carbonyls Alkylated -carbons 1) LDA 2) R-X 3) H3O+/H2O O R1 1) 2°-amine 2) R-X 3) H3O+/H2O R2 O 1) 2°-amine 2) acid chloride 3) H3O+/H2O R4 R3 Michael Reaction various enolates or amines R4 R3 R5 R4 R2 R1 O R3 Nu R4 Nu = enolate forming species or amines R2 R3 esters R1 O O R1 R2 1) R2CuLi 2) H3O+/H2O -Dicarbonyls malonic esters diesters acetoacetic esters Acetoacetic Ester Sythesis Malonic Ester Synthesis Dieckmann Condensation Claisen Condensation R3 1) NaOEt/HOEt 2) H3O+/H2O 1) NaOEt/HOEt 2) H3O+/H2O 1) NaOEt/HOEt 2) R-X 3) NaOH, H2O 4) H3O+/H2O 5) ∆ 1) NaOEt/HOEt 2) R-X 3) NaOH, H2O 4) H3O+/H2O 5) ∆ -ketoesters cyclic -ketoesters alkylated carboxylic acids alkylated methyl ketones O R2 R3 R1 OR4 O O R1 O O R2 R8 O HO R7 R3 R4 R5 R6 O R1 O R1 HO H 3C R1 O R1 H3C R2 Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 R2 Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 Chapter 20 ROADMAP FOR REACTIONS Chapters 20 21 ROADMAP FOR REACTIONS Key: Carbon-carbon bond forming reactions are indicated by reagents written with solid backgrounds and white lettering Chapter 20 Chapter 21 alkene Carbon-carbon bond forming reactions are indicated by reagents written with solid backgrounds and white lettering cyclohexenes dienes HX alkene cyclohexenes dienes HX allylic halides allylic halides quinones benzylic bromides H2CrO4 NBS Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 phenols alkyl benzenes 1) NaOH 2) CO2 3) H3O+/H2O carboxy phenols H2CrO4 aryl carboxylic acids Chapters 20 21 22 ROADMAP FOR REACTIONS Key: Chapter 20 Chapter 21 Chapter 22 ROADMAP FOR REACTIONS Chapters 20 21 22 23 Key: Carbon-carbon bond forming reactions are indicated by reagents written with solid backgrounds and white lettering Chapter 20 Chapter 21 alkene Chapter 22 cyclohexenes Chapter 23 Carbon-carbon bond forming reactions are indicated by reagents written with solid backgrounds and white lettering dienes HX cyclohexenes acyl benzenes X2 , FeX3 R(CO)X, AlX3 HNO3 , H2SO4 nitrobenzenes anilines NaOH, H2O RX, AlX3 X2 , FeX3 R(CO)X, AlX3 halobenzenes HNO3 , H2SO4 1) HNO2 , 2) HCl H2O aryl nitriles KCN, CuCN aryl carboxylic acids aryl diazonium salts KI halobenzenes nitrobenzenes anilines NaNH2, NH3 aryl iodides amines aryl fluorides epoxides 1) KN3 , 2) H2O, 3) LiAlH4 , 4) H3O+/H2O Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 vicinal amino alcohols NaNH2, NH3 HNO2 ketones 1) H2O2 , 2) heat acyl benzenes H2SO4 , SO3 aryl rings H2SO4 , SO3 aryl rings H3PO4 sulfobenzenes H2CrO4 alkyl benzenes 1) excess MeI 2) Ag2O, H2O, heat sulfobenzenes aryl carboxylic acids NBS H2 , Ni H3PO4 H2CrO4 NaOH, H2O alkyl benzenes benzylic bromides RX, AlX3 NBS 3°-ROH, H3PO4 benzylic bromides carboxy phenols H3PO2 phenols 1) NaOH 2) CO2 3) H3O+/H2O carboxy phenols HBF4 H2CrO4 1) NaOH 2) CO2 3) H3O+/H2O H2CrO4 phenols H2 , Ni quinones quinones allylic halides 1) Fe, HCl 2) NaOH HX 1) Fe, HCl 2) NaOH dienes 3°-ROH, H3PO4 alkene allylic halides alkenes This is an electronic version of the print textbook Due to electronic rights restrictions, some third party content may be suppressed Editorial review has deemed that any suppressed content does not materially affect the overall learning experience The publisher reserves the right to remove content from this title at any time if subsequent rights restrictions require it For valuable information on pricing, previous editions, changes to current editions, and alternate formats, please visit www.cengage.com/highered to search by ISBN, author, title, or keyword for materials in your areas of interest Important notice: Media content referenced within the product description or the product text may not be available in the eBook version Copyright 2018 Cengage Learning All Rights Reserved May not be copied, scanned, or duplicated, in whole or in part WCN 02-200-203 ... 20 .3 The Cope Rearrangement Pericyclic reaction. Redistribution of six electrons in a cyclic transition state converts a 1,5-diene to an isomeric 1,5-diene ‡ 3, 3-Dimethyl1,5-hexadiene 6-Methyl-1,5heptadiene... conditions, 1 , 3- butadiene can function as both a diene and a dienophile Draw a structural formula for the Diels-Alder adduct formed by reaction of 1 , 3- butadiene with itself 20 .33 1 , 3- Butadiene is... whole or in part WCN 0 2-2 0 0-2 03 Problems 933 20 .37 Draw a structural formula for the product of this Diels-Alder reaction, including the stereochemistry of the product 20 .38 Following is a retrosynthetic