Exercises meeting nov 6th of 2021 when i was a scientist

exercises about paper

1. M eeting Student : MSc . Christian Leonardo Herrera Advisor : Professor Dr. Carlos R. D. Correia Universidade Estadual de Campinas Institute of Chemistry Organic Chemistry Department Campinas, November 6 th

2. Summary Part I: Total synthesis of brevianamide A key steps : Diels Alder reaction Part II: Total synthesis of terpenes via palladium catalysed cyclization strategy

3. Part I: Total synthesis of Brevianamide A It is a potential insecticidal It belongs to the Family of bicyclo [2.2.2] diazoctanes alkaloids dioxopiperazines Isolated by Birch and Wright in 1969 from the fungus penicillinium brevicompactum In 1970 was proposed a biosynthetical route by using of Diels Alderase enzymes Issues: Biosynthetical routes produced the minor diastereoisomer (B). Insurmountable issues of reactivity and selectivity No Diels Alderase enzymens has yet not been identified to dioxopiperazines alkaloids

4. Part I: Total synthesis of Brevianamide A Previous biosynthetic proposals

5. Part I: Total synthesis of Brevianamide A Question 1: 1. Brevianamide A and B were synthetized from L -Tryptophan for the first time, 50 years ago from their discovery . Discuss the synthetic route and fill in the blanks with relevant information (reagents, reactional conditions, etc.). 2. Previous works in the literature about the synthesis of Brevianamide B used Diels Alderase enzymes in order to obtain the desired product. Is it necessary?

6. Part I: Total synthesis of Brevianamide A What is the reactional mechanism for this step? Reverse prenylation reaction of Danishefsky

7. Part I: Total synthesis of Brevianamide A Lindel, T., Bräuchle, L., Golz, G., Böhrer, P., Org. Lett. 2007 , 9, 2, 283 Shiozawa , M., Iida, K., Odagi , M., Yamanaka, M., Nagasawa, K. J. Org. Chem. 2018 , 83, 13, 7276 Reverse prenylation reaction of Danishefsky mechanism

8. Part I: Total synthesis of Brevianamide A Advantages 34% overall yield for 5 steps ( Previous synth: 12 steps, 8 %) 2 chromatographic purification. Undesired product: amide hydrolysis

9. Part I: Total synthesis of Brevianamide A

10. Part I: Total synthesis of Brevianamide A

11. Part II: Total synthesis of terpenes via palladium catalysed cyclization strategy Nature’s cyclase phase via cationic polyene cyclization Head- tail cyclization Tail-head cyclization Decalin-containing structures Steroid and non-steroid triterpenes Undesired S N 1 and E1 reactions. Necessity of stronger acidic conditions Non tolerance of oxygen functionalities

12. Part II: Total synthesis of terpenes via palladium catalysed cyclization strategy Mimicking nature’s order : Two phases : Cyclization to functionalization Issues : Construing C-C in the absence of functional group is not straightforward There is not yet a general C-H oxidation What would happen it if we inverted the order ? Advantages : Functionalization is easier Construing new C-C are well stablished . Improving redox economy . We could stablish some sterepcenters .

13. Part II: Total synthesis of terpenes via palladium catalysed cyclization strategy

14. Part II: Total synthesis of terpenes via palladium catalysed cyclization strategy Question 2: Propose the mechanism of the cycloisomerization using Palladium

15. Part II: Total synthesis of terpenes via palladium catalysed cyclization strategy Question 2: 1. Propose a synthetic route to prepare the starting material 2. Propose the mechanism of the cycloisomerization using Palladium Mechanism ?

16. Part II: Total synthesis of terpenes via palladium catalysed cyclization strategy Question 2: Trost , M., Bartlett, M., Acc. Chem. Res. 2015 , 48, 3, 688

17. Part II: Total synthesis of terpenes via palladium catalysed cyclization strategy Question 2: 2. Propose a plausible mechanism for the cascade enyne cycloisomerization catalyzed by Palladium

18. Part II: Total synthesis of terpenes via palladium catalysed cyclization strategy Question 2: