Chiral ligand and chiral induction Ziegler Natta catalysis Examples of homogenous catalysis

1. WELCOME
PRESENTED BY
DIVYA V
2ND SEMESTER M PHARM
PHARMACEUTICAL CHEMISTRY
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2. CONTENTS
• Chiral ligands and chiral induction.
• Ziegler-Natta catalysts.
• Some examples of homogenous catalysis used in synthesis of drugs.
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3. CHIRAL LIGANDS AND CHIRAL
INDUCTION
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4. • Chiral ligands are used in asymmetric synthesis.
• Ligand when chelation with metal center form asymmetric catalyst.
• Catalyst transfers chirality to the non-chiral substrate resulting in chiral product with
one enantiomer in excess.
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5. CATALYTIC CYCLE
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6. FIRST CATALYTIC ASYMMETRIC SYTHESIS-SYNTHESIS OF L-DOPA
OH
OH
OH
NH
CH3
O
O
Rh
-P
+
P
+
MeO
OMe
H2
OH
OH
OH
NH
CH3
O
O
OH
OH
OH
O
NH2
L-DOPA
An enamide
[Rh(DiPAMPCOD)]BF4
-
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Deprotection of amine

7. • Chiral ligands examples
P P
MeO
OMe
PPh2
PPh2
O
O
CH3
CH3
PPh2
PPh2
H
H
DiPAMP BINAP DIOP
P
P
R
R
R
R
DuPHOS
OH
OH
BINOL
O
O
CH3
CH3 OH
PhPh
Ph
Ph
OH
TADDOL
N
N
OH CH2
O
CH3
M
NH
OO
N
H
t
-
Bu
t
-
Bu
CINCHONA ALKALOIDS SALEN COMPLEX
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1
4

8. REDUCTION
• Classic asymmetric transformation is reduction of alkenes.
• Ligands-(R)BINAP,(R,R)DIOP,(S,S)DUPHOS
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9. • CARBONYL GROUPS
• Useful for substrate with a second functional group.
• OXIDATION
• Explained by Sharpless asymmetric epoxidation.
CH3
X
O
n
CH3
X
OH
n
H2,BINAP-Ru(II)
X=NR2,-OH,-COOR
R
2
OH
R
3
R
1
R
2
R
1
OH
R
3
OTi(Oipr)4,CHCl2, -200
CH3
CH3
CH3
O
O
CH3
90%ee
EtOOC
COOEt
OH
OH
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10. MECHANISM
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11. • CATALYTIC DIHYDROXYLATION
• Using osmium tetroxide.
• N-Methyl-morpholine is used as stoichiometric oxidant.
• MECHANISM
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OH
OH
OSO4-NMO
+ OsO4
H2O

12. CHIRAL INDUCTION
It describes the formation of an excess of one enantiomer over the other
from an achiral or racemic substrate using a chiral catalyst or chiral reagent is
called chiral induction.
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13. 13

14. ZIEGLER-NATTA CATALYSTS
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15. • It is a catalyst formed by combination of transition metal of group 1-8
with organometallic compound of group 1-3.
• Used for the polymerization of olefins.
• Named after Karl Ziegler and Giulio Natta.
• Metal catalyst, like TiCl3 , co-catalysts are involved,like aluminum.
Most of the time our catalyst/co-catalyst pair are TiCl3 and
Al(C2H5)2Cl, or TiCl4 with Al(C2H5)3.
Ti Cl
Cl
Cl
Cl
and Al
CH3
CH3CH3
TiCl4 and Al(C2H5)3
Ti
+
Cl
Cl
Cl and Al
CH3
CH3
Cl
TiCl3 and Al(C2H5)2Cl
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16. +
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17. 17

18. MECHANISM
• Activation of Ziegler-Natta catalyst.
• Initiation step
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19. • Propagation Step
• Termination step
Termination approaches: (a) β-
elimination from the polymer
chain, forming metal hydride; (b)
hydrogenation
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20. APPLICATIONS
Production of;
HDPE,LDPE
POLYBUTYLENE,CRYSTALLINE POLYPROPYLENE
THERMOPLASTIC POLYOLEFINS
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21. 21

22. EXAMPLES OF HOMOGENOUS CATALYSIS
USED IN SYNTHESIS OF DRUGS
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23. • SYNTHESIS OF L-DOPA
OH
OH
OH
NH
CH3
O
O
Rh
-P
+
P
+
MeO
OMe
H2
OH
OH
OH
NH
CH3
O
O
OH
OH
OH
O
NH2
L-DOPA
An enamide
[Rh(DiPAMPCOD)]BF4
-
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24. • SYTHESIS OF (R) NAPROXEN
• SYNTHESIS OF (S) IBUPROFEN
OH
OCH2
O
CH3
(S)BINAP-Ru(0C0CH3)2
H2 , MeOH
OH
O
O
CH3
CH3
3-(6-methoxynaphthalen-2-yl)but-3-enoic acid (3R)-3-(6-methoxynaphthalen-2-yl)butanoic acid
CH3
CH3
OH
O
H
BINOL-Rh
ipr2NET
CH3
CH3
OH
O
H
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25. • SYNTHESIS OF (R) CITRONELLAL
CH3 N
CH3
CH3
CH3
CH3
Rh-BINAP
1000
C
CH3
CH3
CH3
N
CH3
CH3
H30+
CH3
CH3
CH3
H
O
(R) Citronellal
N,N-diethyl-3,7-dimethylocta-
2,6-diene
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26. REFERENCES
• J.Halpern.Asymmetric catalytic hydrogenation;mechanism and origin
of enantioselection.Asymmetric synthesis.Vol-5 chapter-2.Academic
press;1985.
• J.A.Osborn.F.H Jardine.J.F.Young et.al.J.Chem.soc;1996:171.
• Hisao Nishiyama.Takashi Nakamura.Mihoko Horihata.Chiral and C2
asymmetrical catalyst for hydrosilation of
ketones.Organomettalics;1989:846-848
• www.sigmaaldrich.com
• www.wikipedia.org
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27. THANK YOU
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