carbon of carbonyl compoundsreactions at the α carbon of carbonyl compounds regioselective...
TRANSCRIPT
Reactions at the α
Carbon of Carbonyl
Compounds
Formation of Regioselective Enolates
Synthesis of g-keto esters:
Enamines can also be used in Michael
additions:
NCN+
N
CN
EtOH
reflux
O
H2OCN
Summary of Enolate Chemistry
O
R
H
+ :B
Resonance-stabilized
enolate
O
R
O
RH:B +
.1Formation of an Enolate:
Racemization:
Ph
OR'
HR
Enantiomers
Ph
OH
R
R'OH
or H3O
Enol(achiral)
Ph
OR'
RH
OH
or H3O
Halogenation of Aldehydes & Ketones:
O
RR'
H
O
RR'
X
+ X2
acid
or base
Specific example: haloform reaction:
O
PhH
H
O
Ph
X
+ 3 X2
OH
H2O
X
X
O
Ph OCHX3 +
H
Halogenation of Carboxylic Acids: The HVZ Reaction:
O
OHR
O
OHR
X
1. X2, P
2. H2O
Direct Alkylation via Lithium Enolates:
Specific example:
O
H(R')
O
H(R')
LDA, THF
R
(formation of thekinetic enolate)
RR'' X
O
H(R')R
-78oC
R''
O O Li O
CH3ILDA, THF
-78oC
Direct Alkylation of Esters:
O
OEtR
O
OEtR
LDA
THF
R' BrO
OEtR
R'
Acetoacetic Ester Synthesis:
O
OEt
1. NaOEt
2. RBr
O O
OEt
O
RO
1. OH, heat
2. H3O+
3. heat, ( CO2)R
O
OEt
1. tBuOK
2. R'Br
O O
OEt
O
O
R
RR R'
R'
1. OH, heat
2. H3O+
3. heat, ( CO2)
Malonic Ester Synthesis:
O
OEt
1. NaOEt
2. RBrEtO
O O
OEtEtO
O
R
HO
O1. OH, heat
2. H3O+
3. heat, ( CO2)R
O
OEt
1. tBuOK
2. R'BrEtO
O O
OEtEtO
O
HO
O
R
RR R'
R'
1. OH, heat
2. H3O+
3. heat, ( CO2)
Stork Enamine Reaction:
1.
2. heat3. H2O
O
RR + R'2NH R
NR'2
R
R R
O
R''
R'' Br
Enamine