1. Condensations (J&F Ch. 19) Fischer’s Glucose Proof - Introduction
Chemistry 125: Lecture 73 April 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

2. -Alkylation Ketones / Aldehydes (e.g. J&F Sec.19.5a)?
CH3-I

3. Electrostatic Potential
p attack
HOMO favors C
-143
-170
s attack
Electrostatic Potential
favors O

4. -Alkylation Ketones / Aldehydes (e.g. J&F Sec.19.5a)
(CH3)3Si-Cl
Si(CH3)3
t-Bu
negligible
85%
CH3
negligible
major
CH3-I

5. -Alkylation Ketones / Aldehydes (e.g. J&F Sec.19.5a)
pKa 32
pKa ~20
Ph3C- K+
CH3OC2H4OCH3 +
22%
CH3I (2 eq)
added to enolate solution
House and Kramar, JOC, 38, 3368 (1963)
Org. Syn. Coll vol 76, p. 239, 1999
41% 9%
21% 6%

6. -Alkylation Ketones / Aldehydes (e.g. J&F Sec.19.5a)
i-Pr2N- Li+
-78°C
“LDA”
MnCl2 • 2LiCl
-78°C
PhCH2Br (1.3 eq)
room temp
House and Kramar, JOC, 38, 3368 (1963)
Org. Syn. Coll vol 76, p. 239, 1999
88% distilled
“Org. Syn. Prep.”

7. -Alkylation Carboxylic Acids (e.g. J&F Sec. 19.5b)
i-Pr2N- Li+
“LDA”
LDA
R-Br R

8. -Alkylation -Dicarbonyls (e.g. J&F Sec.19.5c)
HO-
EtO-
R-L
(not HO-)
b-ketoester
EtO-
HO-
R-L
malonic ester
HO-
EtO-
R-L or
cyanoacetic ester

9. -Alkylation Decarboxylation (e.g. J&F Sec. 19.5d)
“Acetoacetic Ester Synthesis” of Ketone
“Malonic Ester Synthesis” of Acid H+ D
Arndt-Eistert, C N, Grignard/CO2 add one C to chain; these syntheses & add two.

10. The Aldol “Condensation” (e.g. J&F Sec 19.6)
b-Hydroxyaldehyde
“aldol”
HOH
HO-
acetaldehyde
favorable equilibrium
-H2O
H+ catalysis also works for both steps
a,b-Unsaturated Aldehyde

11. The Aldol “Condensation” (e.g. J&F Sec 19.6)
Boil
Condense
b-Hydroxyketone
HO-
HOH
ketone
unfavorable equilibrium
Make tea by pouring hot water through tea bag in funnel?
Better to use Soxhelet extractor
containing solid base, Ba(OH)2

12. The Crossed Aldol “Condensation” (e.g. J&F Sec 19.6)
can’t form
enolate!
favorable equilibrium
unfavorable equilibrium
b-Hydroxyketone
HO-
HOH
a,b-Unsaturated Ketone
-H2O

13. Conjugate Addition (e.g. J&F Sec 19.6c)

14. Robinson Annulation - 1935 (e.g. J&F Sec 19.11)
Robert Robinson
R. B. Woodward
by permission J. D. Roberts
pinacol
rearr.
aldol
pinacol
reduction
conjugate addition to
Methyl Vinyl Ketone

15. The Claisen “Condensation” (e.g. J&F Sec 19.8)
starts like aldol
but has a leaving group
b-Ketoester
-RO-
RO-
ester
RO-
Drives the Equilibrium
“eats the lye”

16. Nature’s Claisen “Condensation” (e.g. J&F Sec 19.10)
Malonyl-coA
CO2- 2
Acetyl-coA
unfavorable equilibrium
HScoA =
-CO2
Drives the Equilibrium
1) Reduce
2) Dehydrate H
3) Reduce
Natural fatty acids have even numbers of C atoms.

17. Carbohydrate
(C•HOH)n
CHOH
CHOH
CHOH H OH
CHOH
CHOH
CHOH
Couper
1858

18. Carbohydrate
(C•HOH)n
CHOH
C=O H
CHOH
C=O H
C=O
CHOH H
CHOH

20. Heinrich Kiliani

21. End of Lecture 73 April 25, 2011
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