please don’t do problem 31a, but please do problem 32c
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Please don’t do problem 31a, butplease do problem 32c
Chapter 22 Alpha Substitutions and Condensations of Enols and
Enolate IonsActually this the chemistry ofhydrogen atoms
C
O
H
Aldehydes, ketones and esters
BaseC
O
C
O-
enolate ion
IMPORTANT: enolate is a nuke; attacks via of its alpha carbon
Reactions of Enolates with Electrophiles
C
O-X2
O
X
RCH2X
O
R
OR
R O
R
OH
R
ALDOL REACTION - Borodin
C
EXAMPLES
H
O
CH2
CH3
Dangle the groupattached to alpha carbon
+ H CH2CH3
O
H
O
CH
CH3
nuke portionElectrophilic portion
C
OH
H
CH2CH3H
O
CH
CH3
MECHANISM OF ALDOL REACTION
H CH2
O
H CH3
O+
H
O
CH3
O-
H
HOH-OH-
H
OH
H CH3
O
OH-
CH3
O-
H
In general:
Designing Self Aldol Synthesis
Ph
O
Me
OH
Ph
MeH
H
H
break bond; add H to left portion
Ph
O
Me
HH
remove H from OH then form C=O
O
Me
H
H
Ph
+
R'
O
R2
H
OH
R1
R2
H
H
R1
O
R2
H
H
Acid Catalyzed Aldols
H
O
HH
H
H+
H
O
H
H
OH
HH
H
H
H
O
H
H
H
HH
Conjugated enones quite stable
- HOH
Also called -unsaturated aldehyde
Overall Reaction
H
O
CH3
HH O
H
CH2CH3
H
O
CH3
CH2CH3H
CH2CH3
Other conditions for dehydration of beta hydroxy aldehydes
1. Base plus heat
OH
HH2 OH1
heat OH
H OH OH
heat
-HOH
Planning a Self Aldol synthesis of -Unsaturated aldehyde
Add O Add 2 H
CH3CH2CH=O
CH3CH2CH=CCHOCH3
CH3CH2CH=O
Aldols Involving Ketones
Much slower than aldehydes - need special gimmicks
Me CH2-H
O
Ba(OH)2
refluxMe CH2
O
CH3
OH
Me
DIACETONE ALCOHOL!!!!
Me
O Me
Me
mesityl oxide!!!
Crossed Aldol Condensations-Problems
Two different aldehydes or ketones
PROBLEM - if both have alpha hydrogens
HCCH3
O
nucleophile
+ HCCH2CH3
O
electrophile
HCCH2
O
CCH2CH3H
OH
Problem, con’t
HCCH2CH3
O
nucleophile
+
HCCH3
O
electrophile
HCCH
O
CH3
C-CH3
OH
H
Also self aldol product of acetaldehyde and propionaldehyde
How to get a single crossed aldol product?
1. Treat one of the aldehydes or ketones with -hydrogens with another aldehyde or ketone without -hydrogens.
Commonly used carbonyl compouds without -hydrogens
HCH
O
HCPh
O
HCC(Me)3
O
Of course, these will serve as electrophilic centers
Examples
Trick is to add compound with hydrogen to basic solution containing the compound without hydrogen.
HCCH2
O
CH2CH3 + HCPh
O
OH-
HCCH
O
CHPhCH2CH3
OH
ProblemCan the following compound be prepared in good yield by an aldol condensation?
HO
CH2H
O
H
HO
CH2Me
O
Me
H
Ph
O
Aldol Cyclizations
R
OH
R-OH
OR
R-
OH_ OH_
1,4-diketone
Please do problem 22-30
O
O
R
R'
H
Example 1
CH3
O
O
CH3
AB
Site A to C=O leads to 4-membered ring
Site B to C=O leads to 6-membered ring FAVORED
OO
OH
EXAMPLE -2
O
O
A
B
C D
D to C=O give 6-membered ring
OHMe
O
Me
O
Example 3
O
O
O
HO
H
O
Example Starting diketone?Show the diketone that would give the following
O
2 HO
O
O CH3
Claisen Condensation IMPORTANT POINTS
PKA OF ALPHA H’S ON ESTER ARE AROUND 24 (RECALL KETONES ARE AROUND 20.
THIS REQUIRES THE USE OF A SLIGHTLYSTRONGER BASE
3. USE ALKOXIDES RO- WHERE R IS SAME AS THE OR OF THE ESTER (RECALL PKA OF ALCOHOLS ARE AROUND 17 TO 18.
Claisen CondensationsInvolves Esters with Alpha
Hydrogens
keto ester
R'OC-CH-R
O
R-CH2C
O
OR' R-CH2C
O-
OR'
R'OC-CH-R
OR-CH2C
O
R'OC-CH-R
O
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