Chemistry 125: Lecture 73
April 25, 2011
-H Reactivity
Condensations
Fischer’s Glucose Proof Introduction
(J&F Ch. 19)
(J&F Ch. 19)
This
For copyright
notice see final
page of this file
-Alkylation
Ketones / Aldehydes
(e.g. J&F Sec.19.5a)
CH3-I
?
p attack
HOMO
favors C
-143
-170 s attack
Electrostatic
Potential
favors O
-Alkylation
Ketones / Aldehydes
(e.g. J&F Sec.19.5a)
Si( 3
CH
t-Bu
)3
t-Bu
major
negligible
t-Bu
negligible
85%
(CHCH
3)3Si-Cl
3-I
t-Bu
Si(
)3
-Alkylation
Ketones / Aldehydes
(e.g. J&F Sec.19.5a)
pKa ~20
pKa 32
Ph3C- K+
+
CH3OC2H4OCH3
CH3I (2 eq)
added to enolate solution
22%
41%
9%
21%
6%
-Alkylation
Ketones / Aldehydes
(e.g. J&F Sec.19.5a)
“LDA”
i-Pr2N- Li+
-78°C
MnCl2 • 2LiCl
-78°C
PhCH2Br (1.3 eq)
room temp
88% distilled
“Org. Syn. Prep.”
-Alkylation
Carboxylic Acids
(e.g. J&F Sec. 19.5b)
“LDA”
i-Pr2N- Li+
LDA
R-Br
R
-Alkylation
-Dicarbonyls
(e.g. J&F Sec.19.5c)
R-L
HO-
EtO-
R-L
HO-
EtO-
R-L
HO-
EtO(not HO-)
-ketoester
malonic ester
cyanoacetic ester
or
-Alkylation
Decarboxylation
(e.g. J&F Sec. 19.5d)
“Acetoacetic Ester Synthesis” of Ketone
H+
D
“Malonic Ester Synthesis” of Acid
H+
D
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
HOH
favorable equilibrium
-H2O
“aldol”
H+ catalysis
also works for
both steps
,-Unsaturated Aldehyde
The Aldol “Condensation”
(e.g. J&F Sec 19.6)
Condense
-Hydroxyketone
HO-
ketone
HOH
unfavorable equilibrium
Make tea by pouring
hot water through tea
bag in funnel?
Better to use
Soxhelet extractor
containing solid
base, Ba(OH)2
Boil
The Crossed Aldol “Condensation”
(e.g. J&F Sec 19.6)
can’t form
enolate!
HO-
-Hydroxyketone
HOH
unfavorable
equilibrium
favorable equilibrium
-H2O
,-Unsaturated Ketone
Conjugate Addition (e.g. J&F Sec 19.6c)
Robinson Annulation - 1935
(e.g. J&F Sec 19.11)
aldol
pinacol
reduction
conjugate addition to
by permission J. D. Roberts
pinacol
rearr.
R. B. Woodward
Methyl Vinyl Ketone
Robert Robinson
The Claisen “Condensation”
(e.g. J&F Sec 19.8)
starts like aldol
RO-
but has a leaving group
-Ketoester
-RO-
ester
Drives the Equilibrium
“eats the lye”
RO-
Nature’s Claisen “Condensation”
(e.g. J&F Sec 19.10)
2
CO2-
Acetyl-coA
Malonyl-coA
HScoA =
CO2-
unfavorable equilibrium
Drives the Equilibrium
1) Reduce
2) Dehydrate
3) Reduce
H
Natural fatty acids have even numbers of C atoms.
CO2-CO2
Carbohydrate
(C•HOH)n
CHOH
CHOH
HOH
CHOH
CHOH
CHOH
Couper
1858
CHOH
Carbohydrate
(C•HOH)n
H
CHOH
H
CHOH
H
C=O
CHOH
CHOH
C=O
CHOH
CHOH
C=O
CHOH
CHOH
CHOH
CHOH
CHOH
CHOH
CHOH
CHOH
CHOH
CHOH
CHOH
CHOH
H
CHOH
H
CHOH
H
CHOH
Heinrich Kiliani
1855-1945
End of Lecture 73
April 25, 2011
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J. M. McBride, Chem 125. License: Creative Commons BY-NC-SA 3.0