Cascade reactions

Cascade reactions

1. Presentation on Cascade reaction Department of chemistry, University of Rajshahi

2. Cascade reaction

3. Presentation outline Definition of cascade reaction. Example of cascade reaction. Classification of cascade reaction Mechanism

4. Cascade Reaction Cascade reaction is a chemical process that comprises at least two consecutive reaction such that each subsequent reaction occurs only in virtue of the chemical functionality formed in the previous step. In cascade reaction, Isolation of intermediate is not possible Reaction condition do not change among the consecutive steps of cascade No reagents are added after the initial step A cascade is also called tandem reaction or domino reaction

5. A cascade (also called tandem, also called domino) reaction must satisfy three criteria: Multiple transformations are achieved in a single pot. In this single pot, a single set of reaction conditions is maintained. Each transformation is dependent on the preceding transformation. Cascade Reaction

6. Cascade Reaction Examples: Synthesis of the natural product pentalenene . Asymmetric synthesis of  tetra -substituted cyclohexane carbaldehydes. The total syntheses of (–)-morphine. Synthesis of naturally occurring alkaloid (–)- vindorosine . The total synthesis of (–)- colombiasin . Synthesis of a tigliane by cycloaddition cascade

7. Classification of cascade reaction It is very difficult to classified cascade reaction due to the diverse nature of the many steps in the transformation. K. C. Nicolaou classified as follows:

8. Nucleophilic/electrophilic cascades Nucleophilic/electrophilic cascades are defined as the cascade sequences in which the key step constitutes a nucleophilic or electrophilic attack. A nucleophilic cascade was also employed in the total synthesis of the natural product. A subcategory of nucleophilic/electrophilic sequences is constituted by organocatalytic cascades. Organocatalytic cascades reaction is a reaction in which the key nucleophilic attack is driven by organocatalysis .

9. Nucleophilic/electrophilic cascades Example: synthesis of the broad-spectrum antibiotic (–) chloramphenicol, reported by Rao et al. Hydrolysis (–)-Chloramphenicol

10. Organocatalytic cascades Example: An organocatalytic cascade was employed in the total synthesis of the natural product harziphilone , reported by Sorensen et al. in 2004.

11. Organocatalytic cascades Harziphilone

12. Radical Cascade Radical cascades are those in which the key step constitutes a radical reaction.  The high reactivity of free radical species renders radical-based synthetic approaches decidedly suitable for cascade reactions. the synthetic utility of radical cascades is the cyclization sequence employed in the total synthesis of (±)- hirsutene , in 1985 A cascade radical process was also used in one of the total syntheses of (–)-morphine

13. Radical Cascade Example: synthesis of (±)- hirsutene . (±)- hirsutene .

14. Pericyclic Cascade Pericyclic reactions include cycloadditions, electrocyclic reactions and sigmatropic rearrangements. Although some of the abovementioned instances of nucleophilic/electrophilic and radical cascades involved pericyclic processes, this section contains only cascade sequences that are solely composed of pericyclic reactions or in which such a reaction arguably constitutes the key step. A representative example of a pericyclic cascade is the endiandric acid cascade reported by Nicolaou et al. in 1982

15. Pericyclic Cascade Synthesis of endiandric acid derivatives.

16. Transition metal-catalyzed Example: Rhodium-catalyzed hydroformylation cascade for the preparation of 4 H -chromens. 4 H -chromen

17. References Cascade Reactions in Organic Chemistry - Baran Lab ( https://baranlab.org/wp-content/uploads/2018/02/Cascade_reactions_Reisberg2018.pdf ) Wikipedia ( https://en.wikipedia.org/wiki/Cascade_reaction )