Bachelorprüfung. Organische Chemie III

Transcription

1 Bachelorprüfung rganische Chemie III J Prof. Dr. E. M. Carreira 7. August 2008 ame: Legi-r: Studiengang: Bitte lesen Sie sich die folgenden Aufgaben aufmerksam durch. Beginnen Sie jede Aufgabe auf einem neuen Blatt Papier. Begründen Sie 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 oder mehrdeutige Lösungen werden bei der Korrektur nicht berücksichtigt! Punkte Aufgabe 1 Aufgabe 2 Aufgabe 3 Aufgabe 4 Aufgabe 5 Gesamtpunktzahl: ote:

2 QUESTI 1 (5 points) In the total synthesis of ( )-Sarain A by the verman group, the following reaction was performed: ( )-Sarain A a) Draw product 3 with the predicted configuration at the C4 stereogenic center. b) Give a reaction mechanism including all necessary intermediates. Explain the stereochemical outcome of this reaction by using an appropriate representation of the transition state. c) What is the product if the corresponding (Z)-pent-2-enoate is employed? Rationalize your answer by drawing the corresponding transition state. LDA: Lithium diisopropylamine, DME: Dimethoxyethane

3 QUESTI 2 (4 points) In 2007, the group of J. Mulzer reported the total synthesis of Pasteurestin A, which involves the following diastereoselective reaction: Bn Br SnCl 2, LiAl 4, TF, rt; then 4; then -78 C, 5 78%, de > 99% 4 6 Bn TMS 3 Pasteurestin A TMS 5 a) In the very first step, Sn II is reduced by LiAl 4 to form Sn 0, which then reacts with 4. Give a plausible mechanism and the product of the reaction of Sn 0 with 4. b) Draw a representation of the transition state of the reaction, which explains the configuration at C3 in product 6. TMS: Trimethylsilyl

4 QUESTI 3 (7 points) In the synthesis of Welwitindolinone A Isonitrile, John L. Wood and his coworkers faced the challenge of a diastereoselective α-chlorination of a ketone. Welwitindolinone Isonitrile Treatment of the lithium enolate 7 with -chlorosuccinimide provided the undesired chlorinated isomer 8 in a 7:1 diastereomeric ratio. 7 8 By changing the acetate group on the α-hydroxy ketone to a TIPS group and conducting the reaction with the TBS-silylenolether 9 instead of the corresponding Li-enolate 7 the desired product 10 was obtained as a single diastereoisomer a) Explain the stereochemical outcome of the first reaction by using an appropriate representation of the transition state involved. b) ow do the TBS- and TIPS-group change the outcome of the reaction? Provide drawings of the intermediates that rationalize your answer. CS: -Chlorosuccinimide; TBS: Tert-butyldimethyl silyl; TIPS: Tri-iso-propylsilyl

5 Later in the synthesis a surprising regiochemical problem occurred in the hydroboration of olefin 11. The reaction of 11 with B 3 provided the unexpected Markovnikov product 12 as the major product. Cl Cl B 3, TF 0 C to RT 11 12? Cl? B 3, TF 0 C to RT 13 a) Give a rationale why alkene 11 afforded the unexpected regioisomer 12. b) Suggest a modification of 11 (one simple reaction) that would circumvent this problem in the hydroboration step and allow accessing the desired regioisomer 13.

6 QUESTI 4 (4 points) In the synthesis of a natural polyketide by Paterson the following reduction was carried out a) Predict the configuration of the newly formed stereogenic center under the given conditions. b) Explain your prediction by drawing an appropriate 3-dimensional representation of the transition state that accounts for the diastereoselectivity. c) Why do you think the experimentalists specifically used a zinc borohydride in diethyl ether?

7 QUESTI 5 (5 points) In synthetic studies towards FR901483, Sorensen and coworkers examined a diastereoselective elimination reaction. Whereas 16 was inert to the given reaction conditions, slightly modified substrate 17 readily reacted to give a single isomer. Bn S K t Bu, t Bu, 80 C, 2h no reaction 16 S K t Bu, t Bu, 80 C, 1h 97% X + tbu + K 3 S 17 a) What is the product X formed in this reaction? b) What is the crucial intermediate in the reaction of 17 that is not formed in the reaction of 16? c) Give a representation of the transition state that leads to the product X and highlight the crucial interactions.