Organic chemistry

1. 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.
+

2. 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).

3. 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.

4. The dienes
• Can be cyclic , acyclic carring many kinds of substituents.
• Must have s-cis conformation.
• +I substituted dienes are more reactive than others.
CO2 Na
OMe
OTMS
R
Danishef sky diene R= Me, OMe, CH(Me)OMe

5. Cyclopentadiene
• Cyclopentadiene which is well know as a standard diene
can undergoes self D.A at R.T .
• This dimer can be cracked by distillation.
25oC

7. The dienophiles
• Wide range of dienophiles can be used including cyclic,
acyclic and hetero compounds.
• Perfect dienophiles are alkenes conjugated to electron
withdrawing groups such as carbonyl, nitro, cyano,
halogens…etc
• -I groups increase the rate of D.A reaction.
• D.A reaction between alkene and diene without any
substituents can take place but with low yield.

8. The dienophiles
O O O
Br O
O NMe
Me
O 2N
O O O
O
O O O O
F3C CF3 N N N
N Ph
Ph MeO OMe N
Ph
O
O
S O
Ph NC CN
O P
OEt
SiMe3
OEt NC CN

9. How to know its D.A reaction?
• Since it s {4+2} cycloaddition, the product is, six
membered ring, double bond inside the ring ,
conjugate group outside the ring opposite to
double bond.
O O
+ O O
O O

10. 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.

11. Stereochemistry
• The stereochemistry of substituents can be retained in
the product.
• Cyclic dienes must be in s-cis are highly reactive .
CO2 Me CO 2Me
CO2 Me CO 2Me
+
CO2 Me CO 2Me
MeO 2C CO 2Me

12. Endo rule
• D.A between cyclic dienes and dienophiles can lead
two diasteremers, endo and exo.
• Endo product is kinetically controlled product.
• Exo product is thermomdynamically product.

13. Regioselectivity
• Diels-Alder reaction can lead to different structural
isomers.
• Electronic and steric effects of the substituents.
• Position of these groups is the main factor.
• Usually its ortho and para directiong.
X X
Z Z ortho
Z Z
para
X X
Z= electron-withdrawing gruop
x= electron-donating group

14. Regioselectivity
CO 2H
HO2 C
HO 2C
+ +
OHC OHC
CHO
ort ho meta
O
O
Me
Me
+
Me Me
ort ho

15. Catalysed Diels-Alder reaction
• To increase the rate of the reaction.
• To reduce high temperarture and long reaction times.
• To improve the regioselectivity.
• As a source of enetioselectivity.

16. Catalysed Diels-Alder reaction
• Using Lewis acids catalysts (including chiral members).
• AlCl3 and its derivatives, M(OTf), BF3 .OEt…..
• Using organic catalysts (organic molecules can be used
individually or combined with Lewis Acids).
• Imidazolidinone derivatives, thiourea derivatives, BINOL
and its derivatives…..

17. Lewis Acid catalysis
• L.A binding with EWD group then make the dienophile
more electron deficient.
• Then, decrease LUMO energy, strong interaction with
diene`s HOMO.
-
+ SnCl
O O O 4
O
+ +
without catalyst 71 : 29
with SnCl4 93 : 7

18. Asymmetric Diels-Alder reaction
• Preparation of chiral cyclohexene derivatives .
• Using chiral dienes or dienophiles
• Using chiral Lewis Acids.
CO2 Bn CO2 Bn
O
N N
+ O

19. Chiral dienophiles
O
O
Me N R
O
S
O O
R'
R OMe R
N N
O
O O

20. Chiral dienes
• Using chiral dienes is less developing as the use of
chiral dienophiles.
OTMS
R EtO OMe
N O N
O
O
OAc
O
OAc
OAc OAc

21. Chiral Lewis Acids
+ Me CHO CHO
72% OAlCl2
Me
endo:exo
98:2
O O
N O Me
+ +
OH Me
OH
endo : exo
TMSO 93 : 07
O
O
O
O + TiCl4
OTMS

22. References
• Organic chemistry; Clayden, J.; Greeves, N.; Warren, S.;
Wothers, P. Oxford University Press, Oxford, 2006.
• Lewis Acids and Selectivity in Organic Synthesis;
Santelli, M.; Pons, J. CRS Press, USA, 1995.
• Wikipedia.co.uk