Pericyclic reactions

1. 1
PERICYCLIC REACTION
Prepared By :
Mahendra G S
M-Pharm,Pharmaceutical
Chemistry
JSSCP, MYSURU

2. FLOW OF PRESENTATION
Introduction1
Classification2
Mechanism3
Example4
2

3. Introduction
Pericyclic reactions are "Any concerted reaction in which bonds are
formed or broken in a cyclic transitions state”. (electrons move around in
a circle).
i.e. there is a single transition state from start to finish, in contrast to a
stepwise reaction.
Transition state
reaction co-ordinate
Energy
starting
material
product
Concerted reaction
Transition states
reaction co-ordinate
Energy
starting
material product
Multistep reaction
inter-
mediate inter-
mediate
3.Angew. Chem. Int. Edit. 1969, 8(5),343-348.

4. . Pericyclic reactivity can be understood in
terms of frontier molecular orbital (FMO) theory and the outcome
of reactions can be predicted using the Woodward-Hoffmann
rules.
. Pericyclic reactions require light or heat and are completely
stereospecfic; that is, a single stereoisomer of the reactant forms a
single stereoisomer of the product.
Properties of pericyclic reactions:
(a) Little, if any, solvent effect
(b) No nucleophiles or electrophiles involved.
(c ) Not generally catalysed by Lewis acids.
(d) Highly stereospecific.
(e) Often photochemically promoted.
4

5. Classification:
1. Cycloaddition reaction .
2. Electrocyclic ring closing and ring opening
reaction
3. Sigmatropic Rearrangements
4. Cheletropic
5. Group Transfer

6. Cycloaddition reaction
• A cycloaddition is a pericyclic chemical reaction, in which
"two or more unsaturated molecules (or parts of the same
molecule) combine with the formation of a cyclic adduct in
which there is a net reduction of the bond multiplicity." The
resulting reaction is a cyclization reaction. Designated as
[A+B].
• A and B refers to number of atoms containing π-electrons
• Three important classes of cycloaddition reactions
(i) Diels-Alder reaction
(iii) [2+2] Cycloaddition
(ii) [1,3]-Dipolar cycloaddition
6

7. Diels-Alder Reaction
•Reaction between a conjugated diene and dienophile.
• Highly effective method for the formation of cyclohexene ring
•Discovered by Professor Otto Diels and his student Kurt
Alder in 1928 and received Nobel prize in 1950
+
diene dienophile
7J. Am. Chem. Soc.; 2005; 127(43) pp 15002 - 15003;
hv

8. 1) Diene must be in the s-cis conformation:
s-cis s-trans
This will react: But not this:
(ends are too
far apart)
2) Dienophiles with electron-withdrawing groups (EWG) react faster:
Me Me
CO2Me
O
OMe
CO2Me
O
OMe
O
OMe
CO2Me
slow
fast
This is because the electron-
withdrawing group reduces the
LUMO energy and improves the
overlap with the orbitals in the
diene.
8

9. 3) The reaction is stereospecfic:
MeO2C
CO2Me
CO2Me
CO2Me
MeO2C
CO2Me
CO2Me
CO2Me
9

10. FMO Theory
• Cycloaddition can be explained using frontier molecular orbital (FMO)
theory.
• Frontier Molecular Orbital Theory was developed in the 1960s by
Kenichi Fukui who recognised that chemical reactivity can often be
explained in terms of interacting Highest Occupied MOs (HOMOs), Lowest
Unoccupied MOs (LUMOs)
• The alkene (dienophile) component has two electrons is a "single" π-bond.
FMO theory, here, identifies the HOMO and LUMO components of this
system:
10The Journal of Chemical Physics 20 (4): 722.

11. 11
•Likewise, the diene which has four electrons in is conjugated π-system
can have its HOMO and LUMO identified within FMO theory:
The Journal of Chemical Physics 20 (4): 722.

12. •If we examine the phases at
the ends (terminis) of the
diene and dieneophile we
find that the LUMO/HOMO
interactions are phase
matched:
12
•In the FMO diagrams above, the
sizes or coefficients, are all the same
size, but
usually they are of different sizes. The
rule is that the coefficients match as
well: small with small and large with
large.
•Thus, the regioselectivity of the
cycloaddition can be explained

13. [2+2] Cycloaddition reaction
The [2+2] photocycloaddition is a cycloaddition-type reaction –
it generally entails the formation of new molecules by the reaction
of two unsaturated molecules via two atoms from each molecules
(hence "[2 + 2]").
13Polym. Int. 58 (7): 720

14. 1,3 dipolar cycloaddition reaction
•These are 3 atom 4 electron diene which react with dienophile and form 5-member ring
•This is called 1,3 dipole and this cycloaddition reaction called as 1,3 dipolar
cycloaddition reaction
Mechanism
14J. Clayden, N. Greeves, S. Warren, P. Wothers, Oxford, chapter 34, p 867

15. •Molecular rearrangements in which a σ-bonded atom or
group, flanked by one or more π-electron systems, shifts
to a new location with a corresponding reorganization of
the π-bonds are called sigmatropic reactions. The total
number of σ-bonds and π-bonds remain
unchanged. Diffenent type of sigmatropic rearrangement
reaction are-
Sigmatropic Rearrangements
•(3,3)-sigmatropic rearrangement
• (2,3)-sigmatropic rearrangement
•(1,5)-sigmatropic rearrangement
15

16. Claisen rearrangement or (3,3)-sigmatropic
rearrangement
• This is a example of (3,3)-sigmatropic rearrangement
•This is one-step mechanism without ionic intermediate or
any charge
•Similar like a Cycloaddition reaction
16J. Clayden, N. Greeves, S. Warren, P. Wothers, Oxford, chapter 35, p 897

17. Electrocyclic Reactions
An electrocyclic reaction is a reversible reaction that involves ring
closure of a conjugated polyene to a cycloalkene, or ring opening of
a cycloalkene to a conjugated polyene.
For example, ring closure of 1,3,5-hexatriene forms 1,3-
cyclohexadiene, a product with one more ! bond and one fewer "
bond than the reactant. Ring opening of cyclobutene forms 1,3-
butadiene, a product with one fewer ! bond and one more " bond than
the reactant.
17

18. EXAMPLE OF PERICYCLIC
REACTION
18

19. Synthesis of citral
19J. Clayden, N. Greeves, S. Warren, P. Wothers, Oxford, chapter 34, p 897-930

20. Fischer indole synthesis
20J.J. Li, Name Reactions, 4th ed, p 245

21. Pericyclic Reactions in Biological Systems
21J. Am. Chem. Soc.; 2005; 127(43) pp 15002 - 15003;

22. Oxidation of 3-alcohol to carbonyl compund
22J. Clayden, N. Greeves, S. Warren, P. Wothers, Oxford, chapter 34, p 897-930

23. Synthesis of substituted alcohol
23J. Clayden, N. Greeves, S. Warren, P. Wothers, Oxford, chapter 34, p 897-930

24. Diels-Alder reactions: Alkaloid synthesis:
24J. Org. Chem., 2013, 78 (19), pp 9738–9747

25. Synthesis of intermediate of estrone
25J. Clayden, N. Greeves, S. Warren, P. Wothers, Oxford, chapter 34, p 897-930

26. Diels-Alder reactions for the synthesis of
carbohydrate
J. Clayden, N. Greeves, S. Warren, P. Wothers, Oxford, chapter 34, p 897-930

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