Enols and Enolates a Substitutions and Condensations of Ketones and Aldehydes
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Enols and Enolates Substitutions and Condensations of Ketones and Aldehydes O O H O base acid enolate enol
description
Enols and Enolates a Substitutions and Condensations of Ketones and Aldehydes. Tautomerization Accelerated in Acid. a -Halogenation. Reaction Occurs via Enol. Tautomerization Acceleration in Base. Alkylation in Base Reaction with 1 o RX. Using LDA as Base to form Enolate. - PowerPoint PPT Presentation
Transcript of Enols and Enolates a Substitutions and Condensations of Ketones and Aldehydes
Enols and Enolates
Substitutions and Condensations of Ketones and Aldehydes
O OHO
base acid
enolate enol
Tautomerization Accelerated in Acid
-Halogenation
OCl2, HOAc
O
Cl+ HCl
Reaction Occurs via Enol
OCl2, HOAc
O
Cl+ HCl
H+
OH
H
OH
-H+
OH2 OH
ClCl Cl
Cl
enol
Tautomerization Acceleration in Base
Alkylation in BaseReaction with 1o RX
CH3CO2H 5
CH3CCH2CCH3 9
O O
pKa
CH3CCH2COCH2CH3 11
O O
CH3OCCH2COCH3 13
O O
CH3CH2OH 16
carboxylic acid
-diketone
-ketoester
-diester
alcohol
functional group example
aldehyde C H3CH 17O
ketone CH 3CCH3 19
O
Using LDA as Base to form Enolate
O
H Li N
Lithium diisopropylamide
+
O Li
HN+"LDA"
in THF
Alkylation to C=OC-alkylation preferred
O
H1) LDA in THF
2) (CH3)2CHCH2Br
O
CH2CH(CH3)2
O Li
Br
Alkylation Occurs on Less Hindered Side of C=O
O1) LDA, THF
2) CH3CH2I
O
Malonic Ester Synthesis of Carboxylic Acids
O O
O O
H Hdiethyl malonate
R-XRCH2CO2H
H’s are unusually acidic
O O
O O
H Hdiethyl malonate
1) NaOEt, EtOH
2) CH3I3) H3O+ (to hydrolyze esters)
(loss of CO2)
CH3CH2CO2H + 2 EtOH
+ CO2
O O
O O
H H
1) NaOEt, EtOH
2) CH3I3) H3O+ (to hydrolyze esters)
(loss of CO2)
CH3CH2CO2H + 2 EtOH
+ CO2
OEt
O O
O O
H Na
CH3 I
O O
O O
CH3H
H3O+
HO OH
O O
CH3Hheat
H3O+
(-CO2)
Decarboxylation (loss of CO2)
HO OH
O O
CH3HO OH
O O
CH3H
H
-CO2
OH
OH
CH3
H + CO2 tautomerize
CH3OH
O
2 Acidic H’s, 2 Alkylations; Determine the Product of the
Synthesis
EtO OEt
O O
HH
1) NaOEt, EtOH2) CH3CH2Br
3) NaOEt, EtOH
4) CH2Br
5) H3O+, heat
All -keto acids are unstable and Decarboxylate
O
COCH3
O
H3O+, heat
O
+ CH3OH + CO2
Enamines can be Alkylated
Alkylation of an Enamine Position is Activated
Complements LDA Reaction
N H
H3O+, pH = 4
N CH3CH2IN
I
O
O1) LDA, THF
2) CH3CH2I
O
H3O+
LDA vs. Enamine Reaction
O
1) LDA/THF
2) CH3Br
1) HNR2, H3O+ pH 4
3) H3O+2) CH3Br
OCH3
O CH3
Selenation: Formation of -Unsaturated Ketones
O
1) LDA, THF
2)SeBr
3) H2O2
O
+ SeBr
OH
MechanismO
1) LDA, THF
2)SeBr
3) H2O2
O
+ SeOH
OSe Br
H2O2
O
SeO
H
C6H5O
SeC6H5
Synthesis
O O
CH3N
H
O O
CH3N
H
1) LDA, THF
2) C6H5SeBr3) H2O24) CH3NH2, H2O
Aldol Condensation
Enolate Undergoes Nucleophilic Addition
Aldol CondensationDimerization of 3-Pentanone
O
H
NaOCH3, CH3OH O
OH
O
OCH3
O
O
O
CH3OH
0.5 mol equiv. base
Crossed Aldol Between 2 Different C=O Compounds
CH3CH2CHO + CH3CHO1) NaOEt
2) H3O+ 4 Products
Four Possible Condensation Products
Crossed Aldol CondensationO
H1) NaOCH3 in CH3OH
2) CH3CHO3) H3O+
OCHCH3
OH
use full molar equivalent of base to minimize side-products
O HCCH3
O
OCHCH3
OH+
Dehydration of Aldol ProductsO
1) NaOCH3 in CH3OH
2) CH3CHO3) H3O+
OCHCH3
OH
H
CHCH3
O
H2SO4heat
H2O +
Predicting Aldol Dehydration Products
Intramolecular Aldol
O
O
O
OH
H3O+
O
+ H2OA
AB
B
NaOCH3methanol
Predict the Product
O O O CH
O
+NaOCH3
in CH3OH
O O O CH
O
+NaOCH3
in CH3OH
OO
O O
HO O
O O
O ONa CH3OH
Conjugate Addition
1,2 - vs. 1,4 - Addition
Michael AdditionConjugate Addition of Enolate to -
Unsaturated KetoneO
1) LDA, THF
2) O
3) H3O+
O O
Robinson Annulation:Michael Addition followed by Aldol
Consensation
O
O
CH3 1) NaOH, CH3OH
2) O
3) NaOH (-H2O)
O
OCH3
O
O
CH3
H 1) NaOCH3, CH3OH
2) O
3) NaOH (-H2O)
O
OCH3
O
O
CH3 O O
O
CH3
O
HOCH3
O
OCH3
O
H
NaOH-H2O
