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-Alkylation Ketones / Aldehydes (e.g. J&F Sec.19.5a) ? CH3-I
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Chemistry 125: Lecture 73April 25, 2011
-H Reactivity (J&F Ch. 19)
Condensations (J&F Ch. 19)
Fischer’s Glucose Proof - Introduction This
For copyright notice see final page of this file
-AlkylationKetones / Aldehydes
(e.g. J&F Sec.19.5a)
CH3-I ?
-170
HOMO favors C
Electrostatic Potential
attack
attack
favors O
-143
-AlkylationKetones / Aldehydes
(e.g. J&F Sec.19.5a)
CH3
CH3-I(CH3)3Si-Cl
t-Bu
t-But-Bu
t-Bu negligible
85%negligible
major
-AlkylationKetones / Aldehydes
(e.g. J&F Sec.19.5a)
+Ph3C- K+
CH3OC2H4OCH3
22%
CH3I (2 eq)
41% 9% 21% 6%
added to enolate solution
pKa 32
pKa ~20
-AlkylationKetones / Aldehydes
(e.g. J&F Sec.19.5a)
i-Pr2N- Li+
-78°C
MnCl2 • 2LiCl
-78°C
PhCH2Br (1.3 eq)
room temp
88% distilled“Org. Syn. Prep.”
“LDA”
-AlkylationCarboxylic Acids
(e.g. J&F Sec. 19.5b)
i-Pr2N- Li+
“LDA”LDA
R-Br
R
-Alkylation -Dicarbonyls
(e.g. J&F Sec.19.5c)
EtO- HO-R-L
EtO- HO-R-L
HO-EtO- R-L or
-ketoester
malonic ester
cyanoacetic ester
(not HO-)
-AlkylationDecarboxylation
(e.g. J&F Sec. 19.5d)
“Acetoacetic Ester Synthesis” of Ketone
“Malonic Ester Synthesis” of Acid
H+
H+
Arndt-Eistert, C N, Grignard/CO2 add one C to chain; these syntheses & add two.
The Aldol “Condensation”(e.g. J&F Sec 19.6)
Hydroxyaldehyde
HO-
acetaldehyde“aldol”
HOH
Unsaturated Aldehyde
-H2O
H+ catalysis also works for
both steps
favorable equilibrium
The Aldol “Condensation”(e.g. J&F Sec 19.6)
Hydroxyketone
HO- HOH
unfavorable equilibriumketone
Make tea by pouring hot water through tea
bag in funnel?
Better to use Soxhelet extractorcontaining solid base, Ba(OH)2
Boil
Condense
The Crossed Aldol “Condensation”(e.g. J&F Sec 19.6)
Hydroxyketone
HO- HOH
Unsaturated Ketone
-H2O
favorable equilibrium
can’t formenolate!
unfavorable equilibrium
Conjugate Addition (e.g. J&F Sec 19.6c)
Robinson Annulation - 1935(e.g. J&F Sec 19.11)
Methyl Vinyl Ketone
aldol
conjugate addition to
pinacolrearr.
pinacolreduction
Robert Robinson R. B. Woodward
by p
erm
issi
on J
. D. R
ober
ts
The Claisen “Condensation”(e.g. J&F Sec 19.8)
Ketoester
RO-
ester
-RO-
RO-
“eats the lye”
Drives the Equilibrium
starts like aldol but has a leaving group
HScoA =
Nature’s Claisen “Condensation”(e.g. J&F Sec 19.10)
Acetyl-coA-CO2Drives the Equilibrium
unfavorable equilibriumMalonyl-coA
CO2-
2
CO2-
CO2-
H1) Reduce
2) Dehydrate3) Reduce
Natural fatty acids have even numbers of C atoms.
Couper1858
Carbohydrate(C•HOH)n
CHOHCHOH
CHOHCHOH
CHOHCHOH
HOH
Carbohydrate(C•HOH)n
CHOHCHOH
CHOHCHOH
CHOHCHOH
C=OCHOH
CHOHCHOH
CHOHCHOH
H
H
CHOHC=O
CHOHCHOH
CHOHCHOHH
HCHOHCHOH
C=OCHOH
CHOHCHOH
H
H
Heinrich Kiliani1855-1945
End of Lecture 73April 25, 2011
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