A copy of the Level III (FHEQ Level 6) Equation and Data Sheet booklet is provided. The use of hand-held, battery-operated, electronic calculators will be permitted subject to the regulations governing their use which are displayed outside the examination room. The type of calculator used must be specified on the cover sheet of your answer book. KEELE UNIVERSITY EXAMINATIONS, 2014/15 LEVEL III (FHEQ LEVEL 6) Wednesday 14 th January, 09:15 11:15 CHEMISTRY/MEDICINAL CHEMISTRY CHE-30039 ADVANCED ORGANIC CHEMISTRY Section A Answer ALL questions Section B Answer THREE Questions NOT TO BE REMOVED FROM THE EXAMINATION HALL CHE- 30039 Page 1 of 11
SECTION A ANSWER ALL QUESTIONS 1. (a) Silicon substituents are often used as protecting groups in synthesis. Identify three properties of an ideal protecting group. (3 marks) (b) A non-expert in organosilicon chemistry drew the following mechanism to explain the fluoride promoted deprotection of the tertbutyldimethylsilyl (TBS) group in 1: Using your knowledge of silicon chemistry, explain why this mechanism is incorrect and draw the correct mechanism for the conversion of 1 into 2. (5 marks) (c) The TBS protecting group proved unstable when 1 was subjected to concentrated acid. Suggest an alternative silicon protecting group which would be more stable under acidic conditions, and indicate why your choice is more suitable. (2 marks) CHE- 30039 Page 2 of 11
2. Two metal carbenes, 1 and 2, are shown below: (a) Identify the class of carbenes each belongs to, and in each case, explain your answer. (b) Rhodium carbene 4 can be prepared from the reaction of ethyl diazoacetate, 3, and Rh 2 (OAc) 4. Draw a mechanism to show how this occurs - you may use L n Rh to abbreviate rhodium and its other ligands. (3 marks) (c) Triene 5 was subjected to ring closing metathesis (RCM) using the Grubbs G2 catalyst. Despite the potential to form more than one product, a single product was obtained from the reaction. Predict the structure of the product obtained, explaining your choice no mechanism is required. CHE- 30039 Page 3 of 11 (3 marks)
3. (a) Suggest suitable syntheses of both 2 and 3 that begin with the alkene 1, using any reagents required. No explanations are required. (5 marks) (b) An alternative method to prepare 3 is from a ruthenium catalysed transfer hydrogenation reaction from the ketone 4. Briefly, outline the advantages and disadvantages that transfer hydrogenations provide over conventional hydrogenation and suggest two suitable donors that could be used to reduce 4 into 3. (5 marks) CHE- 30039 Page 4 of 11
4. (a) Draw structures for the missing intermediates 3 and 4 in the following synthetic sequence. Your structures should specify relative stereochemistry. (b) Draw structures for the missing intermediates 7, 8 and 9 in the following synthetic sequence. Your structures should specify relative stereochemistry. (6 marks) CHE- 30039 Page 5 of 11
SECTION B ANSWER THREE QUESTIONS 5. (a) Triphenylphosphine (PPh 3 ) is a much stronger nucleophile than triphenylamine (NPh 3 ). Using a suitable diagram, explain this observation. (b) The scheme below shows the reactions of sulfur ylides: (i) Provide suitable reagents 1 and 2 to complete the reactions shown. (2 marks) (ii) Identify product 3 and draw a mechanism to show its formation. (c) When alkene 4 was subjected to a selenolactonisation reaction with benzeneselenenyl bromide two products, 5 and 6, are formed. Separately 5 and 6 were each reacted with 1 equivalent of m-cpba. 5 formed product 7 with the molecular formula shown, whereas 6 gave two products, benzeneselenenic acid and a second product, 8, which contained no selenium. CHE- 30039 Page 6 of 11
(i) Identify the two selenolactonisation products, 5 and 6, and draw a mechanism to illustrate the formation of either 5 or 6. (ii) Identify products 7 and 8 and fully explain the difference in reactivity observed. (6 marks) CHE- 30039 Page 7 of 11
6. (a) When vinylmagnesium bromide, 1, and aryl iodide 2 are reacted in the presence of a nickel catalyst, a Kumada cross-coupling reaction occurs to afford the alkene product 3: (i) The active catalyst for this reaction, the 14 electron species (PPh 3 ) 2 Ni 0, is generated by reduction of the pre-catalyst (PPh 3 ) 2 Ni II Cl 2 with 1. Show how the active catalyst is generated by consecutive transmetallation and reductive elimination reactions. (3 marks) (ii) The catalytic cycle for the reaction is given below: Identify the structures of the catalytic intermediates 4 and 5, and for both species determine: the number of valence electrons, and the formal oxidation state of the nickel. CHE- 30039 Page 8 of 11
(iii) For each of the three reactions shown below, identify the structures of the expected products 6-8 (no further detail is required): (3 marks) (b) When phenyl iodide and ethyl (Z)-but-2-enoate are reacted together in the presence of a palladium catalyst and triethylamine, a Heck reaction takes place to generate a new alkene 9: Given that the active catalyst is Pd 0 (PPh 3 ) 2, draw a full catalytic cycle for this reaction, and thus predict the structure of product 9. Your answer should also fully account for the regiochemistry and stereochemistry expected in alkene 9. (10 marks) CHE- 30039 Page 9 of 11
7. (a) Draw the 4 π molecular orbitals (as combinations of p orbitals) for a conjugated diene. Identify the HOMO and LUMO orbitals. Based on your diagram, explain why a [4+4] cycloaddition reaction between two conjugated dienes is not symmetry allowed under thermal conditions. (b) Draw the kinetically preferred product of the following reaction (with stereocentres defined), and provide a Transition-State diagram that explains your answer. Explain the origin of the predicted regioselectivity. (8 marks) (c) Using appropriate diagrams to illustrate your answer, explain why electron rich dienes react fastest with electron deficient alkenes (dienophiles) in the Diels-Alder cycloaddition and why electron deficient dienes react fastest with electron rich alkenes (dienophiles) in the Diels-Alder cycloaddition. (8 marks) CHE- 30039 Page 10 of 11
8. (a) For the following reactions, perform a Woodward-Hoffman rule analysis to determine the stereochemistry or double-bond geometry in the products. You should use suitable diagrams to illustrate your answer. (2 7 marks) (b) Using a Frontier Molecular Orbital approach, with suitable diagrams to illustrate your answer, explain why a [2+2] cycloaddition reaction between two diene molecules is not symmetry allowed under thermal conditions but can take place using photochemical activation instead. (6 marks) CHE- 30039 Page 11 of 11