Chapter 19

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

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.

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

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, \(\mathrm{H}_{2} \mathrm{NCH}_{2} \mathrm{CO}_{2} \mathrm{H}\) f. butanedioic acid, \(\left(\mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{H}\right)_{2}\) g. 2-methylbutanedioic acid, \(\mathrm{CH}_{3} \mathrm{CH}\left(\mathrm{CH}_{2} \mathrm{CO}_{2}\right.\) \(\mathrm{H}) \mathrm{CO}_{2} \mathrm{H}\) h. 1 -chloro-2-phenylethane

a. When \((+)-\alpha\) -pinene, 25 , reacts with diborane, a dialkylborane, 26 , is formed: When 26 reacts with cis-2-butene in \(\mathrm{CH}_{3} \mathrm{OCH}_{2} \mathrm{CH}_{2} \mathrm{OCH}_{2} \mathrm{CH}_{2} \mathrm{OCH}_{3}\) as solvent, a trialkylborane is produced. Oxidation of this product with \(\mathrm{H}_{2} \mathrm{O}_{2}\) yields isopinocampheot, 27 , and \((-)\) -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 ?

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.

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

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- \(\left.{ }^{2} \mathrm{H}\right)\) c. meso-2,3-dimethylbutanedioic acid d. the diastereomers of the salt from \(D, L\) -1-phenylethanamine and \(D\) -2-hydroxybutanedioic acid (hydroxysuccinic acid)

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

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.

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-1,2dideuterioethane 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.

Compound A racemizes readily on heating to \(100^{\circ}\), but the rate is not affected by chloride ion and is the same in chloroform and ethanoic acid. Racemization in deuterioethanoic acid \(\left(\mathrm{CH}_{3} \mathrm{CO}_{2} \mathrm{D}\right)\) gives only undeuterated racemic A. Devise a mechanism for the reaction in accord with all the experimental facts.