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Kabachnik--Fields reaction
Kabachnik
Presented by:
Research Scholar
NIPER Hyderabad
Flow of Presentation
Kabachnik-Fields Reaction
Introduction
Substrate Scope
Mechanism
Variations
Applications
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Introduction
Multi Component Reactions (MCRs) are convergent reactions.
MCRs are those reactions whereby more than two reactants combine
in a sequential manner to give highly selective products that retain
majority of the atoms of the starting material.
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Kabachnik-Fields Reaction
This MCR was discovered in 1952 independently by Martin I. Kabachnik & Ellis K. Fields
Involves synthesis of -amino phosphonates which is a one-pot, threecomponent reaction using carbonyl compound, amine and dialkyl phosphite.
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Substrate Scope
C-Modification
Base,Alkylation or
Conjugate Addition
Dialkyl
phosphites
- Amino
phosphonate
Carbonyl
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Amine
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Mechanism
O
P
R5
H
O
O
R4
R5
O
H
O
P O
R3
R4
R2
R1
Aminoalkylation of
hydrophosphoryl
compounds
O
P
R
H
O 5
O
R4
O R
3 OH
R4 O P
O R
2
R5
R1 NH2
Alkylamino Alkyl
phosphonic acid
dialkyl ester
Replacement of the
hydroxy group by
the amino group.
nucleophilic amination
High Temperature
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Phospho-containing component
P-H containing compounds
HP(O)(OH)2, H3PO2
H2P(O)OR, R2PHO
(RO)4P-H, P(OR)3
Carbonyl-component
Mainly Aldehydes
e. g., salicylaldehyde
3-indol-aldehydes
Rarely Ketones are used
Catalysis
Energy microwave irradiation itself or in combination with catalyst,
Ionic liquids as solvents, Ultrasonic radiation
Use of appropriate dehydrating agents e.g. MgSO4, molecular sieves
Use of catalysts Lewis acids are effective catalysts; make carbonyl group more electrophilic
Water deactivates the Lewis acidOvercame by co-use of catalyst with dehydrating agent
or by application of catalysts being stable in water, Like some rare earth metal triflates.
e.g. lanthanide triflates/MgSO4, metal triflates/no solvent, scandium (tris-dodecyl sulfate),
TaCl5-SiO2, Ln(OTf)3 ionic liquid, Lanthanide triflates/ionic liquids, SmI2, AlCl3.
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Applications
Antibacterial
H
N
H2N
OH
O
P
OH
O
Alafosfolin L-Ala-L-(P-Ala)
L-Ala
H2N
HOOC
N
COOH
Tetrahydrodipicolinic acid
Transport
Cleavage
OH
O
P
OH
L-(P-Ala)
DAP Dehydrogenase
DAP Epimerase
O
HO
OH
NH2
NH2
Anticancer
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Anti-leishmaniasis
As Herbicides
Anti-leishmanial Activity
Interfere with etherlipid
Metabolism or glycosylphosphatidyl
Inosital anchor biosynthesis
Med. Chem. Commun., 2014, 5, 665-670
Polymer synthesis
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Thrombin Inhibitors
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