This document defines and provides examples of cascade reactions. A cascade reaction involves at least two consecutive reactions where the product of one reaction undergoes the next without isolation of intermediates or changing conditions. Cascade reactions are classified as nucleophilic/electrophilic, radical, pericyclic, or transition metal-catalyzed. Examples provided include syntheses of natural products like pentalenene and morphine using these cascade reaction types.

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 )