Diels alder reaction.power point

Organic chemistry

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

Otto Diels
Kurt Alder

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.
R=Me,OMe,CH(Me)OMe
R
CO
2Na
OMe
OTMS
Danishefskydiene

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.
25
o
C

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
O
O
N
N
NPh
O
O
S
SiMe3
O
2N
Me
O
NMe
O
O
Br
F3C CF
3
Ph Ph
O O
CNNC
NCCN
P
O
OEt
OEt
NN
O O
OMeMeO
O
Ph
O

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 .
+
CO
2Me
CO
2Me
CO
2Me
CO
2Me
CO
2Me
MeO
2C
CO
2Me
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.
Z
Z
X
X X
Z
X
Z
Z=electron-withdrawinggruop
x=electron-donatinggroup
ortho
para

14. Regioselectivity
Me
Me
O
Me
+
Me
O
CHO
OHC OHC
+
ortho meta
+
CO
2H
HO
2C
HO
2C
ortho

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).
•AlCl
3
and its derivatives, M(OTf), BF
3
.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.
OOO
O
SnCl
4
+
-
+ +
71 29
93 7
:
:
withoutcatalyst
withSnCl
4

18. Asymmetric Diels-Alder reaction
•Preparation of chiral cyclohexene derivatives .
•Using chiral dienes or dienophiles
•Using chiral Lewis Acids.
+
O
N N
O
CO
2Bn CO
2Bn

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

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

21. Chiral Lewis Acids
OAlCl
2
+
72%
MeCHO
Me
CHO
endo:exo
98:2
+
O
ON
O
OH
Me
OH
Me
endo:exo
93:07
O
O
O
O
OTMS
TMSO
+TiCl
4
+

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