CHEM3118 and CHEM3918 Synthetic Chemistry – Synthesis Assignment 3
This assignment is marked out of 10 marks in total, and makes up 4% of your final grade for the unit.
Submission: 11:59 pm, Sunday 25th May, 2025 (Week 12) – upload to Canvas site as a single PDF file.
Synthetic chemistry requires us to be familiar with a wide and diverse set of chemical reactions – what reagents we need to accomplish them and how they work (i.e. their reaction mechanisms). One of the key skills that enables success is this field is an ability to search the chemical literature for different reactions: to find precedents and test sources of information to identify reliable reactions that can be used to make a given target molecule.
This final assignment concerns the landmark series of alkene metathesis papers published in the prestigious journal Nature by the Nobel Laureate Schrock and his collaborator Hoveyda:
• Paper A: M. J. Koh, T. T. Nguyen, H. Zhang, R. R. Schrock, A. H. Hoveyda, Direct synthesis of Z-alkenyl halides through catalytic cross-metathesis, Nature, 2016, 531, 459-465 (doi:10.1038/nature17396).
• Paper B: M. J. Koh, T. T. Nguyen, J. K. Lam, S. Torker, J. Hyvl, R. R. Schrock & Amir H. Hoveyda, Molybdenum chloride catalysts for Z-selective olefin metathesis reactions, Nature, 2017, 542, 80-86, (doi:10.1038/nature21043).
• Paper C: T. T. Nguyen, M. J. Koh, T. J. Mann, R. R. Schrok, A. H. Hoveyda, Synthesis of E- and Z- trisubstituted alkenes by catalytic cross-metathesis, Nature, 2017, 552, 347-356 (doi:10.1038/nature25002).
Answer the following questions:
(i) (2 marks) Choose one of the above three Nature papers. Write the key general reaction scheme that summarises the reported alkene metathesis chemistry and in one paragraph summarise the key innovations of the discovery. Clearly explain in a single sentence why the discovery has transformed this type of alkene metathesis reaction.
(ii) (4 marks) Choose any one of the Mo or W-alkylidene complexes described in the paper chosen in part
(i) (it does not need to be the most active catalyst!) Draw its structure and calculate its total valence electron count, showing all working.
(iii) (4 marks) Choose one synthesis of a target molecule with direct relevance in chemical biology or medicine (i.e. it must be a natural product, chemical probe, or drug molecule) using the catalytic chemistry originally described in the Nature paper chosen in part (i). The synthesis of the small molecule must be reported in another paper and so be sure to reference it. Provide a full mechanism for the alkene metathesis reaction involving the Mo- or W-alkylidene catalyst, using the reagents/reaction conditions in the paper. Be sure to explain where this reaction fits into the general synthetic scheme for the target molecule - is it used to prepare a key precursor, intermediate, or final product? Use curly arrow notation as appropriate. Provide only a general mechanism – there is no need to draw the whole target molecular structure if it is too complex. Using properly identified R-groups is acceptable. You may choose to hand-draw and scan your mechanism, or use ChemDraw. Either way, please ensure your mechanism is clearly legible.