Page 270 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg
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250               2.29. 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
     CHAPTER 2              though only the S-enantiomer is pharmacologically active. Suggest methods that
     Stereochemistry,       might be used to obtain or prepare ibuprofen in enantiomerically pure form,
     Conformation,
     and Stereoselectivity  based on processes and reactions discussed in chapter 2.

                                                                  H  CH 3
                                                                     CO H
                                                                        2
                                                   (CH ) CHCH 2
                                                      3 2
                                                        S-ibuprofen

                       2.30. Ab initio MO calculations (HF/4-31G) indicate that the eclipsed conformation
                            of acetaldehyde is about 1.1 kcal more stable than the staggered conformation.
                            Provide an explanation of this effect in terms of MO theory. Construct a quali-
                            tative MO diagram and point out the significant differences that favor the eclipsed
                            conformation. Identify the interactions that are stabilizing and those that are
                            destabilizing. Identify other factors that need to be considered to analyze the
                            origin of the rotational barrier.

                                                 H                      H
                                                      O              H      O
                                               H
                                                 H    H               H     H
                                              E = 152.685 au       E = 152.683 au
                                                 eclipsed            staggered

                       2.31. 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% diastere-
                            oselectivity). Addition of 0.25 equiv. of 4-nitrophenol then gives a 4-
                            nitrophenylphosphoramidate 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.
                       2.32. Use an appropriate computation program to compare the TS energies for hydro-
                            boration of the following alkenes by  CH   BH. Predict the exo:endo ratio for
                                                              3 2
                            each compound. What factor might complicate the interpretation of the exo:endo
                            ratio?








                       2.33. 9-BBN exhibits a high degree of stereoselectivity toward 1,3-dimethyl
                            cycloalkenes such as 1,3-dimethylcyclopentene and 1,3-dimethylcyclohexene,
                            giving exclusively the trans, trans-2,6-dimethyl cycloalkanols. Offer an
                            explanation.
                       2.34. Diastereoselective reduction of a number of 4-alkylideneprolinols has been
                            accomplished. With a silyl protecting group in place, using Raney nickel, the
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