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19.E: More on Stereochemistry (Exercises)

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    Exercise 19-1 Indicate the reagents you would use to resolve the following compounds. Show the reactions involved and specify the physical method you believe would be the best to separate the diastereomers.

    a. 1-phenyl-2-propanamine
    b. 2,3-pentadienedioic acid
    c. 1-phenylethanol

    Exercise 19-2 Using equations, show the reactions whereby the following chiral reagents could be used to resolve aldehydes and ketones. (Review Sections 15-4E and 16-4C.)

    a. (2\(D\), 3\(L\))-2,3-butanediol
    b. Roberts and Caserio Screenshot 19-E-1.png

    Exercise 19-3 The specific rotation of optically pure 2-methylbutanoic acid is \(\left[ \alpha \right]_D \pm 19.34^\text{o}\) (neat) \(\left( t = 21^\text{o} \right)\). Assume that you resolved the racemic acid with \(\left( + \right)\)-1-phenylethanamine and obtained a rotation for the product of \(+10.1^\text{o}\) (neat) \(\left( t = 21^\text{o} \right)\); calculate the enantiomeric purity (in percent) of the resolved acid. What results would you anticipate if you used the \(\left( - \right)\)-amine in place of the \(\left( + \right)\)-amine? What effect on your resolution would there be if the resolving agent contained \(90\%\) of the \(\left( + \right)\)-amine and \(10\%\) of the \(\left( - \right)-amine?

    Exercise 19-4 Suppose one were to try to resolve a mixture of \(D\)-2-butyl \(D\)-2-methoxypropanoate and \(L\)-2-butyl \(D\)-2-methoxypropanoate by careful fractional distillation. How could one follow the degree of separation of these two diastereomers by proton NMR? Be sure to explain exactly what you would be looking for in the NMR spectra and which peaks could be most helpful.

    Exercise 19-5 When optically active 1-phenylethanamine is dissolved in racemic 1-phenyl-2,2,2-trifluoroethanol, the \(\ce{^{19}F}\) NMR resonance shows two sets of doublets separated by \(2 \: \text{Hz}\) at \(56 \: \text{MHz}\). With the racemic amine, only a doublet \(\ce{^{19}F}\) resonance is observed.

    a. Explain the difference between the \(\ce{^{19}F}\) NMR spectra in the optically active and racemic solvents. (Don't forget the \(\ce{-CH-CF_3}\) spin-spin splitting.)

    b. How could such spectra be used to follow the progress of an attempt to resolve 1-phenyl-2,2,2-trifluoroethanol into its enantiomers?

    Exercise 19-6 \(\left( + \right)\)-Alanine and \(\left( + \right)\)-valine have been related in configuration by the following reaction sequence:

    Roberts and Caserio Screenshot 19-E-2.jpg

    Show the structure and configuration of the products in each step, given that \(\left( + \right)\)-alanine has the \(L\) configuration. Is the configuration of \(\left( + \right)\)-valine \(D\) or \(L\)?

    Exercise 19-7 \(\left( + \right)\)-Lactic acid has the \(L\) configuration. On the basis of the following transformations, deduce the absolute configurations of \(\left( - \right)\)-1-phenylethanol and \(\left( + \right)\)-1-phenylethyldimethylsulfonium fluoroborate. Write equations to show the structure and configuration of the products in each step. Reactions 5 and 7 both give E with the same sign of rotation.

    Roberts and Caserio Screenshot 19-E-3.png

    Exercise 19-8 Determine by the sequence rules the priority sequence in the pairs of groups listed.

    a. cyano, \(\ce{C \equiv N}\), vs. carboxamide, \(\ce{-CONH_2}\).
    b. 2-methylcyclohexyl vs. 4,4-dimethylcyclohexyl
    c. 1-propenyl vs. 2-butyl
    d. phenyl vs. 1-cyclohexyl
    e. chloromethyl vs. hydroxymethyl

    Exercise 19-9 Designate the configuration at each asymmetric carbon in each of the following projection or stereo formulas by both the \(D\),\(L\) and \(R\),\(S\) systems:

    a. Roberts and Caserio Screenshot 19-E-4.png

    b. Roberts and Caserio Screenshot 19-E-5.png

    c. Roberts and Caserio Screenshot 19-E-6.png

    d. Roberts and Caserio Screenshot 19-E-7.png

    e. Roberts and Caserio Screenshot 19-E-8.png

    f. Roberts and Caserio Screenshot 19-E-9.png

    Exercise 19-10 Draw "saw-horse" and projection formulas for each of the following compounds, and designate whether the particular enantiomer is erythro, threo, cis, or trans:

    a. (\(S\))-hydroxyphenylethanoic acid
    b. (1\(R\),2\(S\))-1,2-dimethylcyclopropane
    c. (2\(S\),3\(S\))-3-bromo-2-butanol
    d. (2\(S\),3\(R\))-3-amino-2-butanol
    e. (1\(S\),3\(S\))-1,3-cyclohexanediol
    f. (2\(R\),3\(R\))-2-chloro-2,3-dimethylpentanoic acid
    g.* (\(R\))-2,3-pentadiene

    Exercise 19-11 Draw structures for the following compounds in order to unambiguously specify configuration:

    a. the \(Z\) isomer formed from the reaction of phenylmethanamine with 2-butanone
    b. (2\(E\),4\(Z\))-3-chloro-2,4-hexadiene

    Exercise 19-12 How would you name the compounds shown below in order to unambiguously specify both structure and configuration? Use the cis-trans system when possible. Notice that it is wrong to assume that \(Z\) will invariably be cis or \(E\) will be trans in the two systems.

    a. Roberts and Caserio Screenshot 19-E-10.png

    b. Roberts and Caserio Screenshot 19-E-11.png

    c. Roberts and Caserio Screenshot 19-E-12.png

    d. Roberts and Caserio Screenshot 19-E-13.png

    Exercise 19-13* Designate which of the following structures are chiral, prochiral, and/or achiral. Specify which carbon atoms are prochiral centers.

    a. ethenylbenzene (styrene)
    b. cis-2-butene
    c. 2-propanone (acetone)
    d. 2-butanone
    e. glycine, \(\ce{H_2NCH_2CO_2H}\)
    f. butanedioic acid, \(\ce{(CH_2CO_2H)_2}\)
    g. 2-methylbutanedioic acid, \(\ce{CH_3CH(CH_2CO_2H)CO_2H}\)
    h. 1-chloro-2-phenylethane

    Exercise 19-14* One part of the citric acid cycle (Sections 18-8F and 20-10B) in metabolism converts 2-oxobutanedioic acid by way of citric acid to 2-oxopentanedioic acid:

    Roberts and Caserio Screenshot 19-E-14.png

    If the 4-carboxyl carbon of the 2-oxobutanedioic acid is enriched in \(\ce{^{13}C}\), only the 1-carboxyl carbon of the 2-oxopentanedioic acid contains excess \(\ce{^{13}C}\). Explain in general terms how the intermediate citric acid must be labeled to have the \(\ce{^{13}C}\) turn up in the 1-carboxyl of the 2-oxopentanedioic acid.

    Exercise 19-15 Write structures showing the configuration of each of the possible products to be expected from the following reactions.

    a. Roberts and Caserio Screenshot 19-E-15.png

    b. Roberts and Caserio Screenshot 19-E-16.png

    c. Roberts and Caserio Screenshot 19-E-17.png

    d. Roberts and Caserio Screenshot 19-E-18.png

    e.Roberts and Caserio Screenshot 19-E-19.png

    (\(\ce{L}^*\) is a chiral phosphorus ligand attached to \(\ce{Rh}\))

    Exercise 19-16

    a. When \(\left( + \right)\)-\(\alpha\)-pinene, \(25\), reacts with diborane, a dialkylborane, \(26\), is formed:

    Roberts and Caserio Screenshot 19-E-20.png

    When \(26\) reacts with cis-2-butene in \(\ce{CH_3OCH_2CH_2OCH_2CH_2OCH_3}\) as solvent, a trialkylborane is produced. Oxidation of this product with \(\ce{H_2O_2}\) yields isopinocampheot, \(27\), and \(\left( - \right)\)-2-butanol in \(76\%\) enantiomeric purity. Write equations for these reactions and account for the observed asymmetric synthesis.

    b. 3-Methylcyclopentene can be partially resolved by reaction with less than an equimolar amount of \(25\). The residual alkene has an optical activity corresponding to about \(65\%\) enantiomeric purity. Explain how this partial resolution arises. Why is it necessary to use less than an equivalent of \(25\)?

    Exercise 19-17. Which of the following projection formulas represent the same isomer? Write each in its proper form as a Fischer projection formula of 3-amino-2-butanol.

    Roberts and Caserio Screenshot 19-E-21.png

    Exercise 19-18. Draw Fischer projection formulas for all the possible different configuration isomers of the following substances:

    a. 1,2,3,4-tetrachlorobutane
    b. methylethylpropylboron
    c. 2,3-dibromopropanoic acid
    d. 3-bromo-2,5-hexanediol
    e. methyl hydrogen tartrate (a half-ester)
    f. sec-butyl lactate
    g. Roberts and Caserio Screenshot 19-E-22.png

    Exercise 19-19 Predict the stereochemical configuration of the products from each of the following reactions. Write projection formulas for the starting materials and products.

    a. \(D\)-2-butanol with ethanoic anhydride
    b. \(D\)-2,3-dimethyl-3-hexanol with hydrochloric acid
    c. a chiral monoethanoate ester of 1,2,3-propanetriol (with the \(D\) configuration) and aqueous sodium hydroxide
    d. \(D\)-2-bromobutane with sodium cyanide
    e. \(D\)-2,2,4-trimethyl-3-hexanone with bromine and dilute base
    f.* \(D\)-4-methyl-3-hexanone with methylmagnesium bromide

    Exercise 19-20 Write projection formulas for the following compounds and rename them by the \(R\),\(S\) system:

    a. threo-1,2-diphenyl-1-bromo-2-chloroethane
    b. erythro-3-deuterio-2-butanol (or erythro-2-butanol-3-\(\ce{^2H}\))
    c. meso-2,3-dimethylbutanedioic acid
    d. the diastereomers of the salt from \(D\),\(L\)-1-phenylethanamine and \(D\)-2-hydroxybutanedioic acid (hydroxysuccinic acid)

    Exercise 19-21 Explain how one could use techniques for resolution of enantiomers to determine experimentally whether hydrogen peroxide in methanoic acid adds cis or trans to cyclopentene, assuming the possible addition products to be unknown.

    Exercise 19-22 Devise a reaction scheme for relating the configuration of \(\left( + \right)\)-2-butanol to glyceraldehyde. Think carefully about the reaction mechanisms involved in devising your scheme.

    Exercise 19-23 Discuss possible procedures for resolution of ethyl \(D\),\(L\)-lactate (ethyl 2-hydroxypropanoate bp \(155^\text{o}\)) into ethyl \(D\)-lactate and ethyl \(L\)-lactate.

    Exercise 19-24 When trans-2-butene is treated with bromine, it yields a 2,3-dibromobutane which, with zinc in ethanol, regenerates trans-2-butene. Similarly, cis-2-butene gives a 2,3-dibromobutane, which yields cis-2-butene with zinc in ethanol.

    a. Write projection formulas for all the different stereoisomeric 2,3-dibromobutanes.

    b. From your knowledge of the mechanism of bromine addition to alkenes, predict which isomer of 2-butene would be formed from an optically active 2,3-dibromobutane with zinc. Show your reasoning in detail.

    c. Write a mechanism for the reaction of zinc with 2,3-dibromobutane that is in agreement with the stereochemical result of the reaction.

    Exercise 19-25* meso-2,3-Dibromobutane is converted to quite pure trans-2-butene with potassium iodide in acetone, whereas \(D\),\(L\)-2,3-dibromobutane gives cis-2-butene with the same reagent. In contrast, meso-1,2-dibromo-1,2-dideuterioethane yields only cis-1,2-dideuterioethene with potassium iodide in acetone. Explain how the different results can be reconciled without the necessity of postulating fundamentally different mechanisms for the elimination steps.

    Exercise 19-26 It has been found that meso- and \(D\),\(L\)-2,3-butanediols give different mixtures of 2-butanone and 2-methylpropanal on treatment with sulfuric acid. From consideration of the influence of steric hindrance on the detailed mechanism of the reaction, predict which butanediol diastereomer will give more 2-methylbutanal. (The vital stage of the reaction is likely to be where the migrating group is halfway between the old and new positions.)

    Exercise 19-27* It has been stated that \(\left( + \right)\)-tartaric acid is "fully described" by the \(D\)-configuration because, if either asymmetric carbon is reduced to a \(\ce{CH_2}\) group, \(D\)-2-hydroxybutanedioic acid is formed. Which configuration would be assigned to \(\left( + \right)\)-tartaric acid, if either one of the carboxyls were reduced to a methyl group, the hydroxyl next to the remaining carboxyl reduced to \(\ce{CH_2}\), and the product compared to \(D\)- and \(L\)-3-hydroxybutanoic acids?

    Exercise 19-28* Compound A racemizes readily on heating to \(100^\text{o}\), but the rate is not affected by chloride ion and is the same in chloroform and ethanoic acid. Racemization in deuterioethanoic acid \(\left( \ce{CH_3CO_2D} \right)\) gives only undeuterated racemic A. Devise a mechanism for the reaction in accord with all the experimental facts.


    Exercise 19-29 How could you tell whether a chloroform solution of an optically active compound showing a rotation of \(-100^\text{o}\) was actually levorotatory by \(-100^\text{o}\) or dextrotatory by \(+260^\text{o}\)?

    Exercise 19-30 Solutions of optically active 2,2'-diiodobiphenyl-5,5'-dicarboxylic acid racemize at a measurable rate on heating. Racemization of active 2,3,2',3'-tetraiodobiphenyl- 5,5'-dicarboxylic acid goes many thousand times more slowly.

    Make a scale drawing of the transition state (planar) for racemization; deduce from it the reason for the very slow racemization of the tetraiodo diacid. Use the following bond distances (note that the benzene ring is a regular hexagon):

    \[\begin{array}{lcl} \ce{C-C} \: \text{(benzene ring)} & = & 1.40 \: \text{Å} \\ \ce{C-C} \: \text{(between rings)} & = & 1.47 \: \text{Å} \\ \ce{C-H} & = & 1.07 \: \text{Å} \\ \ce{C-I} & = & 2.05 \: \text{Å} \end{array}\]

    The van der Waals' radii of iodine and hydrogen are \(2.15 \: \text{Å}\) and \(1.20 \: \text{Å}\), respectively.

    Exercise 19-31

    a. Compounds of type \(29\) have been found to be resolvable into optically active forms. Explain.

    BPOCchapter19_Page_40_Image_0001 - Copy.jpg

    b. How many stereoisomers would you predict could exist of structure \(30\), provided that the \(\ce{R}\) groups were sufficiently large to prevent free rotation about the single bonds connecting the 1-propenyl groups to the ring?


    Exercise 19-32 Consider the following transformations:

    cyclohexanone-1-\(\ce{^{14}C}\) \(\overset{\ce{Cl_2}, \: \ce{H}^oplus}{\longrightarrow}\) 2-chlorocyclohexanone-x-\(\ce{^{14}C}\) \(\overset{\ce{NaBH_4}}{\longrightarrow}\) trans-2-chlorocyclohexanol-x-\(\ce{^{14}C}\) \(\overset{\text{resolve}}{\longrightarrow}\) (\(R\))-trans-2-chlorocyclohexanol-x-\(\ce{^{14}C}\) \(\overset{\ce{NaOH}}{\longrightarrow}\) cyclohexene-x-\(\ce{^{14}C}\) oxide \(\overset{\ce{HCl}}{\longrightarrow}\) trans-2-chlorohexanol-x-\(\ce{^{14}C}\) \(\overset{\text{resolve}}{\longrightarrow}\) (\(R\))-trans-2-chlorocyclohexanol-x-\(\ce{^{14}C}\).

    Write appropriate structural formulas for each substance, showing clearly at what position (x) the \(\ce{^{14}C}\) is located in each. If necessary, review Sections 15-11C and 15-11D.


    John D. Robert and Marjorie C. Caserio (1977) Basic Principles of Organic Chemistry, second edition. W. A. Benjamin, Inc. , Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, "You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format."

    19.E: More on Stereochemistry (Exercises) is shared under a not declared license and was authored, remixed, and/or curated by John D. Roberts and Marjorie C. Caserio.

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