Chapter 2

Indicate whether the following pairs of compounds are identical, enantiomers, diastereomers, or structural isomers. a. N C ( C O ) C ( O ) C ( C b. CC1(C)C=CCCC1 CC1C=CCCC1 c. O=C1CC2CCC1C2 and O=C1CC2CCC1C2 d. CC(C)(C)CCCS(=O)CCC(C)(C)C e. O=C1C=CC(Cl)C1 and O=C1C=CC(Cl)C1 f. Cl C 1 C C ( Br ) C ( and C C 1 C C C C ( 2.2. Use the sequence rule to specify the configuration of the stereogenic center in each of the following molecules.

Draw structural formulas for each of the following compounds, clearly showing all aspects of the stereochemistry. a. \(E-3,7\)-dimethyl-2,6-octadien-1-ol (geraniol) b. \(R-4-\) methyl \(-4\)-phenylcyclohex-2-enone c. L-erythro-2-(methylamino)-1-phenylpropan-1-ol [(-)-ephedrine] d. \(7 R, 8 S-7,8\)-epoxy-2-methyloctadecane (dispalure, a pheromone of the female gypsy moth)e. methyl \(1 S\)-cyano- \(2 R\)-phenylcyclopropanecarboxylate f. \(Z-2\)-methyl-2-buten-1-ol g. \(E\)-(3-methyl-2-pentenylidene)triphenylphosphorane

Draw the structures of the product(s) described for each reaction. Specify all aspects of the stereochemistry. a. stereospecific anti addition of bromine to cis- and trans-cinnamic acid. b. methanolysis of \(S-3\)-bromooctane with \(6 \%\) racemization. c. stereospecific syn thermal elimination of acetic acid from \(1 R, 2 S\) diphenylpropyl acetate d. stereoselective epoxidation of bicyclo[2.2.1]hept-2-ene proceeding \(94 \%\) from the exo face.

The preferred conformation of 1-methyl-1-phenylcyclohexane has the phenyl group in the axial orientation ( \(\Delta G=-0.32 \mathrm{kcal} / \mathrm{mol}\) ) even though its conformational free energy \((2.9 \mathrm{kcal} / \mathrm{mol})\) is greater than that of methyl \((1.8 \mathrm{kcal} / \mathrm{mol})\). Explain.

Compound 20-A can be resolved to give an enantiomerically pure substance with \([\alpha]_{D}=-124\). Oxidation gives an enantiomerically pure ketone \(\mathbf{2 0}\) - \(\mathbf{B}\), \([\alpha]_{\mathrm{D}}=-439\). Heating \(\mathbf{2 0}-\mathbf{A}\) establishes an equilibrium with a stereoisomer with \([\alpha]_{\mathrm{D}}=+22\). Oxidation of this compound gives the enantiomer of \(\mathbf{2 0}-\mathbf{B}\). Heating either enantiomer of \(\mathbf{2 0}\)-B leads to racemization with \(\Delta G^{\ddagger}=25 \mathrm{kcal} / \mathrm{mol}\). Deduce the stereochemical relationship between these compounds.

When partially resolved samples of \(S-5\)-(hydroxymethyl)pyrrolidin-2-one are allowed to react with benzaldehyde in the presence of an acid catalyst, two products 21-A \(\left(\mathrm{C}_{12} \mathrm{H}_{13} \mathrm{NO}_{2}\right)\) and 21-B \(\left(\mathrm{C}_{24} \mathrm{H}_{26} \mathrm{~N}_{2} \mathrm{O}_{4}\right)\) are formed. The ratio of 21-A:21-B depends on the enantiomeric purity of the starting material. When it is enantiomerically pure, only \(\mathbf{2 1 - A}\) is formed, but if it is racemic only 21-B is formed. Partially resolved samples give 21-A and 21-B in a ratio corresponding to the e.e. The rotation of \(21-\mathbf{A}\) is \([\alpha] D=+269.6\), but \(21-B\) is not optically active. Develop an explanation for these observations including likely structures for 21-A and 21-B. Assign the configuration of all the stereogenic centers in the products you propose. CN1C(=O)CCC1CO

Ibuprofen, an example of an NSAID, is the active ingredient in several popular over-the-counter analgesics. In the United States, it is sold in racemic form, even though only the \(S\)-enantiomer is pharmacologically active. Suggest methods that might be used to obtain or prepare ibuprofen in enantiomerically pure form, based on processes and reactions discussed in chapter \(2 .\)

Treatment of alkylphosphoryl dichlorides with 1 equiv. of \(L\)-proline ethyl ester in the presence of 1-methylimidazole (acting as an acid-scavenger) leads to formation of a monophosphoramidate with low \((<20 \%\) diastereoselectivity). Addition of \(0.25\) equiv. of 4-nitrophenol then gives a 4nitrophenylphosphoramidate with high \((98 \%)\) diastereoselectivity, which in turn can be treated with methanol to isolate the methyl 4-nitrophenylphosphonate ester in high enantiomeric purity. This constitutes a kinetic resolution process. Write a mechanistic scheme that accounts for this series of transformations.

Diastereoselective reduction of a number of 4 -alkylideneprolinols has been accomplished. With a silyl protecting group in place, using Raney nickel, thecis isomers are formed in ratio of about \(15: 1\). When the unprotected alcohols are used with the Crabtree catalyst, quite high selectivity for the trans isomer is found. Explain these results.