Enantioselective Synthesis - Organic Chemistry - Exam, Exams of Organic Chemistry

Download Enantioselective Synthesis - Organic Chemistry - Exam and more Exams Organic Chemistry in PDF only on Docsity! Ollscoil na hÉireann, Gaillimh National University of Ireland, Galway _____________________________ SUMMER EXAMINATIONS 2010 _____________________________ THIRD YEAR UNIVERSITY B.Sc. EXAMINATION IN SCIENCE (INCLUDING DENOMINATED DEGREES) Paper III: Organic Chemistry (CH311) Professor Richard J. K. Taylor Professor Paul V. Murphy Dr. Fawaz Aldabbagh Dr. Peter B. Crowley Dr. Niall W. A. Geraghty Time Allowed: Two Hours Answer four questions from Sections A-D: One from each Section Use a separate answer book for each Section. All questions carry 25 marks distributed as shown. Leave the first page of the answer book blank and list on it clearly the numbers of the questions attempted. 1 Section A (Answer only one question) 1. Answer each of the following: (i) Explain what is meant by the term enantioselective synthesis. [5 marks] (ii) The enantioselective synthesis of a chiral molecule (asymmetric synthesis) can be carried out using three different approaches; using chiral pool molecules, resolution and stereoselective synthesis (catalytic and stoichiometric). Briefly describe these approaches, discussing the advantages and disadvantages associated with each. [12 marks] (iii) Identify the chiral carbon in each of the following reactions and explain how each reaction could be carried out enantioselectively: H2C C CO2H CH2CH3 H3C C CO2H CH2CH3 H H3C C C O H3C C C O CH3 O O CH3 O H OH OH OH O Ph Ph O Ph Ph H OH CH3 CH3 [8 marks] 2. Answer each of the following: (i) Explain the difference between a convergent and a linear synthesis and explain why it is desirable, where possible, that a synthesis should be convergent. Determine the overall yield of a linear synthesis involving four steps, two of which gave yields of 70%, and the other two yields of 90% and 50%. [9 marks] (ii) Describe any two methods of synthesising a six-membered carbocyclic ring, providing an example in both cases. [8 marks] (iii) Carry out a retrosynthetic analysis of the following molecule showing at least three retrosynthetic steps (synthons and synthetic equivalents should be provided where appropriate): H3C H3C CH3 OH [8 marks] 4 [6 marks] (iv) A solution of protein P is stable over the pH range 4.5 - 9.0. When the pH is lowered to 4.0 the solution turns cloudy, indicative of protein precipitation. Explain what is happening with reference to the amino acid composition and the isoelectric point of protein P. [5 marks] 6. Answer each of the following: (i) Name the classes of molecule to which structures I and II belong. Indicate the presence of any stereocentres in structure II. O OH OH OH OH OH CH3 CH3CH2 I II [4 marks] (ii) Draw the energy minimum chair conformation for I and explain the preference for axial and equatorial substituents. Indicate the anomeric carbon and define the stereochemistry at this position. [6 marks] (iii) Discuss the solubility of I and II in the solvents water and diethyl ether [6 marks] (iv) Crystal structure analysis of protein Q reveals a binding site for II. Describe the features of the binding site that will favour an interaction with II. Draw the side chains of two amino acids that are likely to occur in the binding site. [9 marks] Section D (Answer only one question) 7. Answer each of the following: (i) Compare and contrast the influence of the heteroatom in pyrrole, furan and thiophene on (a) the electronic structure of these molecules (b) their reactivity. In your answer clearly indicate (with reasoning) the most favoured position for electrophilic aromatic substitution. [12 marks] (ii) Draw the exo and endo Diels-Alder cycloaddition adducts of the reaction between furan and maleic anhydride (I). Briefly explain why the exo-adduct is the major reaction product. 5 O OO (I) [7 marks] (iii) Provide a mechanism for the following transformation using curly arrows to illustrate your answer (Scheme 1). O O OMeMeOBr2, MeOH Scheme 1 [6 marks] 8. Answer each of the following: (i) Give reasons for the differences in pKa values between molecules A and B and between C and D (Figure 1). [5 marks] (ii) Piperidine E is a far stronger base than pyridine. Give a detailed explanation for this observation and include a discussion of hybridisation. [5 marks] N H N H N H N H pKa = pKa = 5.511.2 35 35 16.515 + Cl _ A B C D E F Figure 1 (iii) Identify heterocyclic products G, H and I from the following reactions (Scheme 2). Write mechanisms for two of the transformations. 6 N CN H N O N H G NaN3, NH4Cl, LiCl DMF, 100 °C H + _ i. HNO3, H2SO4 ii. PPh3 AcONO2, AcOH -10 °C I (major isomer) Scheme 2 [15 marks]