Organic chemistry

1. Pericyclic Reactions II

2. O O
H H
O O
O O
Alder ene reaction

3. Cycloaddition Reactions
Cycloaddition reactions
[2+2] [4+2] 1,3 dipolar C.A
Ene Reaction,Thermal, Diels-Alder Reaction Alkene(2π) +Nitrone 2e
Photo

4. Cycloaddition Reactions
• In this reaction two π bond lost and two σ bonds formed
• One step mechanism, no intermediates (aromatic
transition state*) arrows start from π bond and go around
the ring.
• Can occur thermally or photochemically.
• All cycloaditions are suprafacial ( occur on one face of π
system).

5. Suprafacial and antarafacial geometries
• Suprafacial if overlap occur at two lobes
located on the same side the nodal plane
• Antarafacial if on opposite sides

6. Ene Reaction
• Alder Ene reaction
• Alkene with –I group (enophile) and alkene with allylic
hydrogen.
• Formation of one new C-C and C-H bonds
• No ring formed here ????????
• Mainly , similar features of D.A reaction.
O O
O O
H H
O O

7. Woodward – Hoffmann rules
For Cycloadition reactions
Total number of Reaction Allowed mode
(4q + 2)s and (4r)a conditions of ring closure
Odd number Thermal Suprafacial
Odd number Photochemical Antarafacial
Even number Thermal Antarafacial
Even number Photochemical Suprafacial

8. Enophiles
• Can also be aldehyde, ketone and imines.
• The product in this case is hydroxylated.
R3
S N R4 R2
O
R2 R1 R2 R1 R2 R1 R3 R1
O O
X X
H
H

9. Ene Reaction
• Can be catalyzed by Lewis acids to increase electrophilicity of
enophile.
• Intramolecular ene reaction
MeAlCl2
O
O
H
R R
O OH
H

10. Carbonyl Ene Reaction
• Carbonyl compounds are good enophiles.
• L.A catalysis is possible (lowering LUMO energy)
• Using L. A enhances stereoselectivity.
O O
L.A
MeO MeO
H
O OH

11. Diels-Alder Reaction
Otto Diels Kurt Alder
• Method for synthesis of 6-membered ring
• One-step, concerted reaction
• Termed [4+2] cycloaddition reaction where 4π and 2π
electrons react.
+

12. Diels-Alder Reaction
• Discovered by O. Diels and K. Alder in 1928.
• Occur between a conjugated diene and substituted alkene
(dienophile) to form cyclohexene ring system.
• Concerted reaction (single step), can be accelerated by heating
or using some catalysts.
• [ 4+2 ] cycloaddition reaction.
• In retro Diels-Alder reaction, the six membered ring is break
down to regenerate the diene and dienophile using high
temperature usually.
• Stereoselective reaction ( mainly one product formed).

13. Diels-Alder Reaction
• Stereospecific reaction ( reactants can keep their
stereochemistry).
• No transition states or charged intermediates.
• All electrons moving in same time to form two new σ bonds.
• 100 % economic ( No. of reactants atoms = No. of products
atoms).
• If one or more of diene or dienophile atoms are not carbon ,the
reaction is hetero-Diels-Alder reaction.

14. How it works?
• Concerted reaction via aromatic transition state.
• There are two approches, the first depends on the interaction
between HOMO of The diene and LUMO of the dienophile.
• The second, depends on +I, -I groups affect, since they form
negative and positive cherges on the diene and dienophile.

15. Frontier orbital interactions in
the[π4s+π2s] cycloaddition
ψ4
Antibonding Ψ2‫׳‬ ψ3
ψ3 LUMO Ψ 2‫׳‬
B A
HOMO ψ1‫׳‬
Bonding ψ2
ψ1‫׳‬ ψ2
ψ1
A B
Suprafacial

16. Photochemical [2+2] Cycloaddition
• 4n cycloaddition type (not allowed thermally).
• Light excitation
• Stereospecific reaction
• Forward reaction
ψ2 ψ2‫׳‬
Antibonding HOMO LUMO
LUMO ψ2‫׳‬
HOMO ψ2
Bonding
*

17. Photochemical [2+2] Cycloaddition
• Mechanism of most of theses reactions are not clear
due to isomerisation.
O O O
hv .
.
O O MeO2 C O
CO2 Me CO2 Me
hv
CO2 Me CO2 Me
MeO2 C

18. Regioselectivity
• LUMO - LUMO Interaction
O O
hv
• HOMO - LUMO Interaction
O O-
+
hv
X

19. Thermal [2+2] Cycloaddition
• Mainly, via ketene chemistry.
• Formation four memebered ring.
• Alkene with elecrtophilic alkene
O O
C C C
N
Cl Cl R
O
C heat

20. Frontier orbital interactions in
the[π2s+π2s] cycloaddition
A- Thermal reaction
ψ2
Antibonding
LUMO ψ2
ψ1
Bonding HOMO
ψ1
Suprafacial Antarafacial

21. Thermal [2+2] Cycloaddition
• Cyclopentadiene can react in [2+2] fashion???
faster than Diels-Alder.
O
O
C
NO2
NO2
NC OAc OAc
CN

22. 1,3 dipolar cycloaddition
• [(2╥ +2e) + 2 ╥ ] to form five membered ring
• 1,3 dipolar component and polarophile (substituted alkene).
• Nitrone ( 3 atoms ) + Alkene (2 atoms).
• 4s+2s suprafacail cycladdition
R
+N _ R
O
N
O
O
R

23. 1,3 dipolar cycladdition
• [2+3] means no. of atoms NOT [2+3] cycloaddition
• Other examples of 1,3 dipoles
• Could we say nitrone similar to the diene ???

24. Comparison
• 1.3 dipolar C.A • Diels-Alder reaction
• Nitrone and alkene • Diene + alkene
• [(2╥ +2e) + 2 ╥ ] • [4╥ + 2 ╥ ]
• 3+2 =Five membered ring • 4+2= six membered ring
• Works with simple alkene • HOMO of diene and LUMO
• Use HOMOs or LUMOs, of the alkene.*
depending on the
polarophile

25. 1,3 dipolar cycloaddition
R R
LUMO
+N _ +N _ HOMO
O O
R O LUMO
HOMO
R

26. Ozonolysis
• Cleveage of alkenes with ozone to form carbonyl compounds
mainly.
• So, 1,3 dipolar cycloaddirion
O O
O O O O

27. Ozonolysis
• The product can be controlled by work up step.

28. Ozonolysis
O O
O
O O 1,3 dipolar cycloaddition O O O O
R1 R2 R1 R2
R1 R2
Ozonide carbonyl oxide
O
R1 R1 O
O 1,3 dipolar cycloaddition O
O O
R2 R2
O O R2 Me Me
R1 O SMe2 S
O R1 O O
R2
unstable

29. Oxidation with OsO4
• OsO4, is yellow solid,used as oxidizing agent and as a
catalyst.
• High compatibility for compexation due to multi
oxidation states.
• Os (76e) has 11 different oxidation states,.
O O
Os
O O
R OsO4 R OH
R HO R

30. Mechanism
O O
R Os
O O O O
Os
R
O O
R1 R2
viii
O O
Os HO OH OH
H 2O O O
O O
Os R
R
HO OH R1 R2
R1 R2 OH
vi Sy n
Osmate ester

31. Oxidation with OsO4
• OsO4 can react with both –I ,+I alkenes
• So, it uses HOMO or LUMO*.
• Because of its toxicity and expense, its used with catalytic
amount with co oxidant.
OH O
OsO 4, NMO
t-BuOH, H2 O OH N
Me O

32. References
• Organic chemistry; Clayden, J.; Greeves, N.; Warren, S.;
Wothers, P. Oxford University Press, Oxford, 2006.
• Strategic Applications of Named Reactions in Organic
Synthesis; Korti, L.; Czako, B. Elsevier Press, USA,
2005.
• Wikipedia.co.uk.
• Organic Chemistry Portal.Org