Cascade reactions

1. 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:
1. Multiple transformations are achieved in a single
pot.
2. In this single pot, a single set of reaction conditions
is maintained.
3. 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:
Cascade reaction
Nucleophilic or
Electrophilic
Radical Pericyclic
Transition
metal-catalyzed

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 4H-
chromens.
4H-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 )