Summary RX C RCN N RXR'CC RCCR' alkyne
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Formation of carbon-carbon bonds R X + - C R C N X R R' C C - N R C C R' R C O R' HCN R C OH R' CN R C O R' QMgBr R C OH R' Q Summary R C O OR' 2 QMgBr R C OH Q Q + + (X pl. Cl, Br, I, OTs, OMs) + + O QMgBr + QCH 2 CH 2 OH primary alcohol nitrile alkyne primary, secondary, tertiary alcohols tertiary alcohol cyanohydrine 1
Transcript of Summary RX C RCN N RXR'CC RCCR' alkyne
Formation of carbon-carbon bonds
R X + -C R C N
XR R' C C-
N
R C C R'
R C
O
R' HCN R C
OH
R'
CN
R C
O
R' QMgBr R C
OH
R'
Q
Summary
R C
O
OR' 2 QMgBr R C
OH
Q
Q
+
+
(X pl. Cl, Br, I, OTs, OMs)
+
+
OQMgBr + QCH2CH2OH primary alcohol
nitrile
alkyne
primary, secondary,tertiary alcohols
tertiary alcohol
cyanohydrine1
Aldol addition (aldol dimerization)
R-CH2-CH CH-CHO
R
H
R-CH2-CH-CH-CHO+
β-hydroxy aldehyde (aldol)
OH-O OH
R
CH CO
OEtR CO
OEt R CO
CHQ-COOEt-EtOH
+ H
Q
Claisen condensation
Na
R-CH2-CH
O-
CH
R
CHO
H+
R-CH2-CH-CH-CHO
OH
R
β-oxo-ester
R CO-
CHQ-COOEtOEt
aldol intermediate Claisen intermediate
-EtO-
R CO
CHQ-COOEt 2
Mixed aldol addition with aldehydes
R-CH CH-CHO
Q
H
R-CH-CH-CHO+OH-
O OH
Qacceptor donor
CH
Q
CH
O
CH
Q
CH
O
-H+
R-CH
O
R-CH-CH-CHO
O
Q
H+
structure of enolate ion
CH
Q
CH
O
base
aldol intermediate
3
Examples
O
CH H CH3CH2CH2CHO CH3CH2CH-CHO
CH2OH
+NaOHH2O
formaldehyde butyraldehyde
CH3O CHO CH3CCH3
O
CH3O CH=CH-C-CH3
+
NaOH-H2O30 oC
CH3O CH-CH2-C-CH3
OH O
O-H2O
4
Aldol addition with ketones
O O OH O
O
-H2O
+
O
acetone
cyclopentanone
acid or base
O O
OH+
O
H+(E1)
-H2O H+(E1)
acid or base
5
Intramolecular aldol reaction
OH
O
O
O
O
OH
O
acid or base
enolization
intramolecular aldol reaction
-H2O
6
Mixed Claisen condensation
C
O
OEt CH3CH2COCH3
OC
O
CHCH3
COCH3
O
+
β-oxo-ester
donoracceptor
base-EtOH
CH CO
OEtR CO
OEt R CO
CHQ-COOEt-EtOH
+ H
QNa
β-oxo-ester
R CO-
CHQ-COOEtOEt
Claisen intermediate
-H+
base
CH CO
OEtQ
donoracceptor
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Intramolecular Claisen condensation (Dieckmann condensation)
CH2-COOEt
C-OEt
O
CH-COOEt
C-OEt
O
CH-COOEtC
O OEt
CH-COOEtC
O
-H+ -EtO-
EtO-
diethyl adipate
CH-COOEtC
O
CH-COOHC
OC
O
hydr. heat
-CO28
C
O
EtO CH2 C OEt
O
R CH2 C OH
OR-Br
4 steps
Malonester synthesis
Acetoacetic ester synthesis
C
O
CH3 CH2 C OEt
O
CH3 C CH2
OR-Br
4 stepsR
carboxylic acid
methyl ketone
4 steps: deprotonationalkylationhydrolysisdecarboxylation
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10
Conjugated addition on carbonyl compounds
O
NC OH
O
CN
HCN, 10 oC
HCN, 80 oC
forms faster(kinetic product)
more stable product(thermodynamic product)
HCN addition
O
bigger δ- (faster addition)
C-O 357 kJ/molC=O 748 kJ/mol
smaller δ-
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Michael addition (conjugated addition with a C nucleophile)
C
O
CH2 C
O
HC CH C
O
CH CH2 C
O
CHCC
O O
α,β-unsaturated oxo compound
1,3-dioxo compound
+NaOEt
heteroconjugated system
O O-+
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HC CH CO
C
O
CH C
O δ+
C
O
CH2 C
O
EtO-
CH CH C
O
CHCC
O O
Mechanism
CH CH2 C
O
CHCC
O O
H+-EtOH
base
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Examples
CH3CCH=CH2
O
CH2(COOEt)2 CH3CCH2-CH2-CH(COOEt)2
O
methyl vinyl ketone malonester+
EtO-
H3O+
heating
CH3CCH2-CH2-CH(COOH)2
O
CH3CCH2-CH2-CH2COOH
O-CO2
O
CH3CCH2COEt
O O
acetoacetic ester
O
CH2CCH3
O1. EtO-
2. H3O+,heat+
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NMe2
O
NMe2
O
α,β-unsaturated carboxylic acid derivatives
BuBuLi, -70 - 20oC
OMe
O
OMe
O
H2NNH3
Cl
O
NH2
ONH3
amide
ester
acyl chloride
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Conjugated addition with nitriles
CN
CNEt2N
Et2NH
CN MeNH2CN
MeHN
+
+
NCN
CNMe
CN
CNHO
SHHO
SCN+
acrylonitrile
better nucleophileless nucleophilic FG
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Conjugated substitution
Cl
O
OMe
O
MeOH
Cl
OMeOH
Cl
O- HOMe+
-H+
-Cl-
Cl
Cl O
HN
NH ONH2
good leaving group
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Arndt-Eistert chain elongation (Wolff rearrangement)
R COOHR CH2-COOH
R CH2-COOR'R C
O
Cl
R C
O
CH N N
OC
RCH O C CH R
CH2 N N
-HCl
base, heatR C
O
CH N N
diazoketone
-N2ketene derivative
acyl carbene
H2O
R'OH
R C
O
Cl(diazomethane)
CHR C
OCH2R C
O
OH
CH2R C
O
OR'
