Chem 360 Jasperse Ch. 22 Notes. Enolate Chemistry
Chapter 22 (Enolate Chemistry) Reaction Summary
Chem 360-Jasperse
PROTON as ELECTROPHILE
O
OH
base, ROH
1.
Ph
Ph
-Base-catalyzed keto-enol equilibrium
-know mech (either direction)
-know impact of substituents on enol concentration
O
O
O
base, ROH
2.
*
Ph
+ Ph
Ph
H CH3
CH3 H
H CH3
optically active
racemic
-Racemization of α-chiral optically active carbonyls
-Mech
HALOGEN as ELECTROPHILE
O
O
excess Br2 (Cl2 )
3.
Ph
Ph
base
Br
Br
-Base catalyzed halogenation
-with excess halogen, all α-hydrogens get replaced
-Mech
O
4.
Ph
O
excess I2
excess NaOH
Ph
-Iodoform reaction.
-chemical test for methyl ketones
ONa
O
O
5.
+ CHI3
Br2 (Cl2 )
Ph
acid
Ph
-Acid-catalyzed halogenation
-can achieve selective mono-halogenation
Br
H
1
Chem 360 Jasperse Ch. 22 Notes. Enolate Chemistry
2
ALKYL HALIDE as ELECTROPHILE
O
O
1. LDA
6.
R
Z
2. R-X
Z
-Enolate alkylation
-strong LDA base required to completely deprotonate carbonyl
-Mech
-Ketones, Esters, Amides, Aldehydes: doesn’t matter which kind of carbonyl
-unsymmetrical ketones give isomer problems
-SN2 alkylation restricts R-X to active ones
O
O
O
1. NaOR
7.
OR
O
O
H3O+ , heat
2. R-X
R
OR
R
-Enolate alkylation of 1,3-ketoester
-alkoxide base strong enough to completely generate enolate
-Mech for alkylation
-SN2 alkylation restricts R-X
-position of alkylation is unambiguous
-acid-catalyzed hydrolysis/decarboxylation
O
8.
O
RO
O
1. NaOR
OR
2. R-X
O
RO
O
H3O+ , heat
OR
R
HO
R
-Enolate alkylation of 1,3-diester
-alkoxide base strong enough to completely generate enolate
-Mech for alkylation
-SN2 alkylation restricts R-X
-acid catalyzed hydrolysis/decarboxylation
-Final product is an ACID (Diester Acid)
O
9.
O
Z
OH
R
O
H3O+ , heat
-CO2
O
Z
H
Z
R
O
O
-CO2
O
R
H
Z
R
-decarboxylation of a 1,3-carbonyl acid
-”Z” can be anything so that you end with a ketone, aldehyde, or acid at the end
-know the mechanism for the decarboxylation, and acid-catalyzed enol to carbonyl isomerization
-rate will be impacted by stability of the enol intermediate
Chem 360 Jasperse Ch. 22 Notes. Enolate Chemistry
3
ALDEHYDE/KETONE as ELECTROPHILE
O
10. R
OH
base
H
ROH
R
H
R
-Aldol Reaction
-Mech
O
11. R
O
Z OH
base
O
base, ROH
heat
R
Z
H
Z
O
R
Z
(or acid)
R
R
-Aldol Condensation
-Ketones as well as Aldehydes can be used
-In ketone case, unfavorable aldol equilibrium is still drawn off to enone
-In Aldehyde case, can stop at aldol if you don’t heat
-Mech
Z OH O
12. R
base, ROH
heat
H
Z
O
R
Z
(or acid)
R
R
-Aldol dehydration
-Mech under basic conditions
O
13.
R'
OH
O
H
O
+ R
R'
Z
O
base, ROH
heat
base
Z
(or acid)
R'
R
Z
R
-Crossed Aldol (2 different carbonyls)
-Many variations, but there must be some differentiation so that one acts selectively as the
enolate and the other as the electrophile
-Mech
O
14.
O
O
O
base, ROH
heat
base
H
(or acid)
HO
-Intramolecular aldol
-Mech
-many variations
-Normally only good for 5, 6-membered rings
Chem 360 Jasperse Ch. 22 Notes. Enolate Chemistry
ESTER as ELECTROPHILE
O
15. R
O
base
OR
O
R
ROH
OR
R
-Claisen Reaction
-Mech
-Produces 1,3-ketoester
O
16.
R'
O
OR
O
base
+ R
Z
O
R'
ROH
Z
ketone or ester
R
-Crossed Claisen
-May include cyclic Claisen reactions
-If the “enolate” carbonyl is a ketone, get a 1,3-diketone
-If the “enolate” carbonyl is an ester, get a 1,3-ketoester
-Mech
ENONE as ELECTROPHILE
O
O
17.
+ R
enone
Z
O
O
base
Z
ROH
ketone or ester
R
-Mech
-”Michael Addition”
O
18.
base
+ R
enone
O
O
O
O
Z
ketone or ester
base
Z
ROH
R
ROH
heat
Z
R
-”Robinson Annulation”
-Mech
-Michael addition gives 1,5-dicarbonyl, then intramolecular aldol reaction-dehydration
WITTIG REACTION
O
X
19.
+
A
B
A
Y
B
-Mech
Br
R
-Mech
PPh3+
1. Ph3P
20.
R1
X
PPh3
2. BuLi (or some
other base)
-
R
R1
Y
4