UNIVERSITY OF EAST ANGLIA School of Chemistry Main Series UG Examination 2016-17 ORGANIC COMPOUNDS: SYNTHESIS AND PROPERTIES CHE-6101Y Time allowed: 2 hours Answer THREE questions. You are advised to spend an equal amount of time on each question. All questions carry an equal number of marks. Answer EACH question in a SEPARATE answer book. The breakdown of marks within each question is indicated by the percentage figures in brackets on the right. Do not remove this question paper from the examinations room. Notes are not permitted in this examination. Do not turn over until you are told to do so by the Invigilator. Module co-ordinator: Maria Munoz-Herranz (CHE) Copyright of the University of East Anglia Version 1
2 1. Answer ALL parts (a) to (c). (a) The first 4 steps in the racemic synthesis of Cryptophycin C (not shown) are shown in Scheme 1 below. Scheme 1 State the reagents needed for steps A and D. [20%] (b) Suggest a retrosynthetic analysis (indicating latent polarity, type of disconnection and synthons required) for compound 1 (Scheme 1), and use this to suggest a method for its synthesis (indicating synthetic equivalents and reagents) from dihydrocinnamaldehyde (4, Scheme 1). [30%] question 1 continues / Version 1 22/05/2017 16:17
3 /question 1 continued (c) By considering frontier molecular orbitals and the Woodward-Hoffmann rules, predict which of the following reactions (i-iv) in Scheme 2 below, will proceed more readily (in other words, are they allowed or disallowed). Draw curly arrow mechanisms for each. Scheme 2 [50%] TURN OVER 22/05/2017 16:17 Version 1
4 2. Answer ALL parts (a) to (e). (a) Part of the catalytic cycle for the Hiyama-Denmark coupling reaction is shown below in Scheme 3. Name the steps labelled A and B and identify the missing structures 5, 6 and 7 to complete the labelling of this catalytic cycle. [30%] Scheme 3 (b) What effect does the addition of fluoride to the organosilane starting material 8 (Scheme 3) have on the reactivity of the organosilane in the transmetallation step? [10%] (c) Draw the full mechanism for the reductive elimination step shown in Scheme 3. [10%] (d) Application of the Yukawa-Tsuno equation to the data obtained from the hydrolysis of arylalkynes 9 shown in Scheme 4 below, gives ρ = -5.1 and r = 0.81. Define and explain the meaning of r and ρ. [20%] Scheme 4 (e) Propose a mechanism for the reaction in Scheme 4 and use it to account for the values of ρ and r. [30%] Version 1 22/05/2017 16:17
5 3. Answer ALL parts (a) to (c). (a) For ONE of the following target molecules 10 or 11, suggest a retrosynthetic analysis and the forward synthesis starting with a Diels-Alder reaction. Indicate reagents for each step and the type of reaction required. Pay particular attention to selectivity issues. [50%] O OBn Me OMe Me O Me 10 11 OMe (b) The synthesis of (±)-hirsutene was achieved in a single step by tandem radical cyclisation of precursor 12 as shown in Scheme 5 below. What is the full mechanism for the formation of the radical Bu 3 Sn, using substoichiometric AIBN? Explain why AIBN can be used in substoichometric amounts. (AIBN = azobisisobutyronitrile) [20%] Scheme 5 (c) Draw the full mechanism for the tandem radical cyclisation reaction to form (±)-hirsutene from 12. Classify the cyclisation reactions occurring in this mechanism using the Baldwin nomenclature. [30%] TURN OVER 22/05/2017 16:17 Version 1
6 4. Answer ALL parts (a) to (e). (a) Identify the products 13, 14 and 15 from the three alkene metathesis coupling reactions shown below (i-iii): [30%] (i) (ii) (iii) (b) The formation of the seven-membered ring product 16 shown in Scheme 6 below turned out to be unexpectedly well controlled. Scheme 6 What other monocyclic product might have been expected from this reaction? [10%] question 4 continues / Version 1 22/05/2017 16:17
7 /question 4 continued (c) The diastereoselective aldol reaction of compound 17 bearing an Evan s chiral auxiliary with benzaldehyde (18) gives mainly the syn diastereomer 19 (1:500) as shown in Scheme 7 below via a reactive intermediate (A). What is the structure of this intermediate and how is it formed (draw full mechanism)? [25%] Scheme 7 (d) Draw the full mechanism from A to product 19. By drawing an appropriate transition state model account for the strereoselectivity observed. [25%] (e) Assign the absolute configuration of the two new chiral centres in 19. [10%] END OF PAPER 22/05/2017 16:17 Version 1