School of Science and Sport Physical Sciences, Chemistry Paisley Campus Session 2014-15 Trimester 2 MDULE CDE: CHEM10003 RGANIC CHEMISTRY 4 EXAM Date: 15th May 2015 Time: 10.00am 12.00pm Attempt THREE UT F FIVE QUESTINS.
May 2015 Start of Exam Attempt THREE UT F FIVE QUESTINS. 1 The achiral alpha, beta unsaturated carboxylic acid (I) was treated with a camphor derivative to give the intermediate (II). Treatment of (II) with a methyl organocuprate reagent resulted in asymmetric conjugate addition of a methyl group. The product (III) was obtained in 92% enantiomeric excess after hydrolysis of the chiral auxiliary. CH 2 CH 3 H 3 C CH 3 CH 2 CH 3 H H 3 C CH 2 CH 3 H (I) H 3 C H (II) Bu t 1) MeCu.P(n-Bu) 3 BF 3.Et 2 2) Hydrolysis H (III) a) Explain what is meant by the following terms (in bold) with respect to the above synthesis. The achiral carboxylic acid (I) chiral auxiliary Asymmetric conjugate addition 92 % enantiomeric excess b) Explain how you think the chiral auxiliary induces asymmetry into the conjugate addition of the methyl group. (2) c) Define what is meant by a prochiral centre and identify the prochiral centre in the intermediate II (3) d) Define what is meant by the terms re and si face with respect to the prochiral centre in (II). Define which face is re and which face is si and hence identify the face which is attacked by the methyl group in the conjugate addition. (5) Question 1 continues overleaf Page 2 of 7
e) Define what is meant by an asymmetric centre and identify the asymmetric centre in the product (III). Assign the configuration of the centre as R or S, showing clearly how you obtain your answer. (3) f) Explain how you might synthesise the opposite enantiomer of (III). (3) 2 Use retrosynthetic analysis to devise a synthetic route to the molecules below from simple starting materials Your answer should also include a full description of the structure of the target molecule and an explanation of your chosen route. (20) a) b) c) d) e) Page 3 of 7
3 ne step in a 10 step synthesis of a natural product is shown below. a) Write out a reaction mechanism this reaction (3) b) Why does this choice of reagents ensure that regiochemical control is achieved? (3) c) The reaction was attempted again with an alternative set of reagents and conditions, including a weak base (NaH), a protic solvent (ethanol) and at room temperature over 24 hours. A different isomeric product was formed. Explain this observation. (2) d) Briefly discuss any difficulties that might be found in trying to control stereochemistry in the above reaction. (2) e) Examine the above reaction and discuss it in terms of the principles of Green Chemistry, highlighting both good and bad points. (10) Page 4 of 7
4 a) Briefly explain the 18 electron rule in relation to transition metal chemistry and deduce whether the following palladium complex satisfies this rule. (2) Ph 3 P Pd PPh 3 Ph 3 P PPh 3 b) Explain the general scope of the Heck reaction and describe the catalytic cycle involving palladium. In your answer you should highlight the key catalytic steps and the roles of reagents and reactants at each stage of the mechanism. (14) c) Provide suitable starting materials and reagents that could be employed to prepare the following molecules using either a Suzuki or Sonogashira cross coupling reaction. (4) H N 2 Page 5 of 7
5 a) i) State whether pyrrole is more or less acidic than pyrrolidine and indicate the molecules pka values. Explain your answer by drawing the resonance structures of the heterocycles conjugate bases. (4) Pyrrole Pyrrolidine ii) Draw and arrange the furan, pyrrole and thiophene rings in order of reactivity towards electrophilic aromatic substitution. Discuss why pyrrole and thiophene rings show different reactivity towards electrophilic reagents. (3) iii) Draw a schematic representation of the orbital structure of pyrrole and furan rings indicating which electrons are located in the π cloud and which ones are located in the sp 2 orbitals. (3) b) i) At which position of their frameworks do pyridine rings undergo electrophilic aromatic substitution? In the scheme below, draw the resonance structures of the reaction products, explain which position is the preferred one for electrophilic attack on the pyridine ring and indicate the least stable resonance contributors. (5) Question 5 continues on next page Page 6 of 7
ii) At which position of their frameworks do pyridine rings undergo nucleophilic aromatic substitution? In the scheme below, draw the resonance structures of the reaction products, explain which position is the preferred one for the nucleophilic attack on the pyridine ring and indicate the most stable resonance contributors. (5) End of Exam Page 7 of 7