You are advised to spend an equal amount of time on each question.

Transcription

1 UNIVERSITY OF EAST ANGLIA School of Chemistry Main Series UG Examination TOPICS IN ORGANIC CHEMISTRY CHE-6151Y 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: Sean Bew (CHE) Copyright of the University of East Anglia Version 1

2 2 1. Answer ALL parts (a) to (d). (a) Provide a comprehensive curly arrow mechanism that accounts for the reaction between the alkyne and the azide shown below under the condition given. Explain your answer and include the structure(s) of the product(s) you expect, the name of the reaction and any regiochemistry you consider important. [50%] (b) Provide a definition for TWO of the following terms (i)-(iv), including in your answers an illustrative example. (i) Iterative deconvolution in combinatorial chemistry. (ii) Diversity-oriented synthesis. (iii) A lead-like structure for drug discovery. (iv) A scavenger for use in a flow synthesis. [30%] (c) Give two advantages of the use of a solid-phase support in organic synthesis. What is a disadvantage of this approach? (d) Give two advantages of a continuous-flow synthetic procedure over an alternative stepwise batch procedure. Version 1 30/01/ :06

3 3 2. Answer ALL parts (a) to (e). The following scheme illustrates a one-pot three component synthesis of an imidazo[1,2-a]pyridine under microwave irradiation. (a) How does microwave irradiation help promote this reaction, and why might the choice of DMF as solvent be important? [15%] (b) Draw a mechanism to account for the generation of the imidazo[1,2-a]pyridine. [20%] (c) Suggest a modification to this procedure for a split-and-mix combinatorial synthesis of a library of imidazo[1,2-a]pyridine derivatives of general structure 1 from the starting materials indicated. Suggest a linker group and give a method for its removal. How many compounds will there be in the resulting library? [15%].../question 2 continues.../ TURN OVER 30/01/ :06 Version 1

4 4.../question 2 continued (d) Explain the meaning of the term monoterpene in natural product chemistry. (e) Geranylgeranyl diphosphate is the acyclic precursor for terpenoid natural product verticillene (drawn below). (i) Choosing either the E or Z isomer, as required, show how geranylgeranyl diphosphate can be folded into a conformation that can be cyclised in the active site of a terpene synthase to produce this natural product. [15%] (ii) Using the curly arrow formalism, draw a mechanism for this multistep cyclisation reaction (the details of the enzyme active site are not required in your answer, and you may use A-H and B: to represent acid and base functionality without attributing them to specific amino acid side-chain groups). [25%] Version 1 30/01/ :06

5 5 3. Answer ALL parts (a) to (d). (a) (i) Provide a comprehensive curly arrow mechanism for the reaction between all three starting materials outlined below and include the product of the reaction. [45%] (ii) What is the name of this reaction? [5%] (b) 1,3-Propanediol (2) reacts with tert-butyldimethylsilyl chloride and potassium tert-butoxide to generate the desired product A and by-product B. What are the structures of A and B? (c) Compound A reacts to produce C when treated with the reagents outlined below. With the aid of curly arrows draw the reaction mechanism for this transformation highlighting the key intermediates. [35%] (d) Compound C can be converted into D using TBAF (tetra-n-butylammonium fluoride). What is the structure of TBAF and D? [5%] TURN OVER 30/01/ :06 Version 1

6 6 4. Answer ALL parts (a) to (e). (a) Compound 3 reacts with cesium fluoride to generate a highly reactive intermediate E. What is the structure of E? (b) Compound E reacts further in the presence of a palladium(0) catalyst affording F and G. What are the structures of F and G? (c) Highlighting key intermediates draw a comprehensive curly arrow mechanism that accounts for the formation of F or G. [30%] (d) Identify the missing intermediates in the sections of multistep biosynthetic pathways shown below: (i) The conversion of geranyl diphosphate into a precursor for the natural product thujone. Identify H and I. question 4 continues.../ Version 1 30/01/ :06

7 7.../question 4 continued (ii) The conversion of humulene into a precursor to hirsutic acid. Identify J and K. (iii) The conversion of squalene oxide into -amyrin. Identify L and M. (e) Choose ONE of the examples of terpene biosynthesis given in part (d) and draw, with mechanisms, the sequence of steps that correspond to this interconversion. [20%] END OF PAPER 30/01/ :06 Version 1