Bachelorprüfung. Organische Chemie III

Transcription

1 Bachelorprüfung rganische Chemie III J Prof. Dr. E. M. Carreira 10. ktober 2006 ame: Legi-r: Studiengang: Bitte lesen Sie sich die folgenden Aufgaben aufmerksam durch. Beginnen Sie jede Aufgabe auf einem neuen Blatt Papier. Begründen Sie jeweils Ihre Antworten kurz in Stichworten. Versichern Sie sich, dass auf jedem abgegebenen Blatt Ihr ame sowie Ihre Legi-ummer steht. Zeitdauer: 60 Minuten Wichtig: Unleserliche resp. mehrdeutige Lösungen werden bei der Korrektur nicht berücksichtigt! Punkte Aufgabe 1 Aufgabe 2 Aufgabe 3 Aufgabe 4 Aufgabe 5 Gesamtpunktzahl: ote:

2 Question 1 In 1990, Evans et al. published the total synthesis of the polyether antibiotic ionomycin. The following transformation led to the synthesis of an important chiral building block Bu 2 BTf, Et 3, -78 C 2. Bn % dr = 95: , int: Tf = trifluoromethanesulfonate a) Predict the major product with the correct absolute configuration. b) Explain the stereochemical outcome of the process using appropriate three-dimensional models, and briefly discuss your proposal.

3 Question 2 In the same synthesis, the following transformation between amide 4 and iodide 5 was used to prepare a different chiral building block equiv. LDA, TF, -78 C 2. I % dr = 98:2 a) Predict the major diastereomer witht the correct absolute configuration. b) Explain the stereochemical outcome of the process using appropriate three-dimensional models, and briefly discuss your proposal. c) Suggest a reason why Evans and coworkers might have used a different auxiliary instead of the standard oxazolidinone-derived Evans -auxiliary, to perform this reaction.

4 Question 3 In 1984, eathcock et al. performed extensive studies on the diasterofacial selectivity in Lewis-acid mediated reactions between allylsilanes and chiral enones. Allylation of trans-enone 7 using allyltrimethylsilane 8 gave product 9 in 82% yield as a 8:1 mixture of diastereomers favoring the cisisomer. + Si equiv. TiCl 4 C 2 Cl 2, -78 C 90 min % dr = 7:1 a) Provide a detailed mechanism of this transformation taking into consideration all relevant components of the reaction mixture. b) Explain the stereochemical outcome of the transformation with appropriate three-dimensional models. Briefly discuss your proposal. When cis-enone 10 is used in the reaction, the selectivity is reversed, and the trans-isomer 11 is predominantly formed. + Si equiv. TiCl 4 C 2 Cl 2, -78 C 90 min % dr = 10:1 c) The change from the trans-enone 7 to the cis-enone 10 results in the trans-isomer 11 being the major product. What might be the reason for this? int: You do not have to provide a detailed model that gives a rationale for the observed selectivity.

5 Question 4 In 1999, MacMillan et al. developed the following Lewis-acid catalyzed reaction between the tertiary allylic amine 12 and the acid chloride mol% TiCl 4, i Pr 2 Et + Cl C 2 Cl 2, 23 C % dr > 99:1 a) Provide a detailed mechanism of this transformation taking into consideration all relevant components of the reaction mixture. int: The acid chloride first reacts with the added base to form a reactive intermediate which then reacts further. b) Explain the stereochemical outcome of the process using appropriate three-dimensional models. Briefly discuss your proposal.

6 Question 5 In 2006, Kerr et al. published the first enantioselective synthesis of (+)-phyllantidine. In the course of the synthesis, it was necessary to perform the following selective hydroxylation of intermediate 15. PMB PMB PMB 15 C 2 PMB KMDS, TF, -78 C Ts Davis oxaziridine PMB C 2 16a (major) PMB C 2 16b (minor) 80% 16a : 16b = 3 : 1 a) Provide a detailed mechanism of this transformation taking into consideration all relevant components of the reaction mixture. int: KMDS = potassium hexamethyldisilazide PMB = para-methoxybenzyl The hydroxylation proceeds with a diastereoselectivity of 3:1 in favor of product 16a. b) Explain this stereochemical outcome with the help of a detailed conformational analysis of the intermediate, and briefly discuss your proposal.