Download Please don`t do problem 31a, but please do problem 32c

Please don’t do problem 31a, but
please do problem 32c
Chapter 22 Alpha Substitutions
and Condensations of Enols and
Enolate Ions
Actually this the chemistry of a-hydrogen atoms
O-
O
O
H
Base
C
Aldehydes, ketones and esters
C
C
enolate ion
IMPORTANT: enolate is a nuke; attacks via of its alpha carbon
Reactions of Enolates with
Electrophiles
O
X
X2
O-
O
RCH2X
C
R
O
R
O
OH
R
R
R
ALDOL REACTION - Borodin
C
EXAMPLES
O
O
H
CH2
+ H
CH2CH3
CH3
Dangle the group
attached to alpha carbon
O
OH
H
CH
C
CH3
H
CH2CH3
nuke portion
Electrophilic portion
MECHANISM OF ALDOL
REACTION
O
+
CH2
H
O
O
H
OCH3
H
OH-
CH3
H
O
H
HOH
-OH-
CH3
O
H
OH
H
CH3
In general:
O
OH
O
H
R'
R1
R2
H
Designing Self Aldol Synthesis
O
O
H
H
+
O
Me
OH
H
H
H
Ph
Ph
R2
R1
H
R2
H
H
H
Me
Ph
Me
Ph
Me
H
break bond; add H to left portion
remove H from OH then form C=O
Acid Catalyzed Aldols
O
O
H
H
OH
H
H+
H
H
H
H
H
H
H
H
- HOH
O
H
H
H
H
Also called a,b-unsaturated aldehyde
H
H
Conjugated enones quite stable
Overall Reaction
O
H
H
H
H
CH3
O
CH2CH3
CH2CH3
O
H
H
CH3
CH2CH3
Other conditions for dehydration
of beta hydroxy aldehydes
1. Base plus heat
2
H
OH1
-HOH
H
O
H
heat
H OH
O
H
heat
O
H
Planning a Self Aldol synthesis
of a,b-Unsaturated aldehyde
CH3CH2CH=CCHO
Add O
CH3CH2CH=O
CH3
Add 2 H
CH3CH2CH=O
Aldols Involving Ketones
Much slower than aldehydes - need special gimmicks
O
O
OH
Ba(OH)2
CH2-H
Me
O
Me
reflux
Me
CH2 Me CH3
DIACETONE ALCOHOL!!!!
Me
Me
mesityl oxide!!!
Crossed Aldol CondensationsProblems
Two different aldehydes or ketones
PROBLEM - if both have alpha hydrogens
O
O
HCCH3 + HCCH2CH3
nucleophile
electrophile
OH
HCCH2 CCH2CH3
H
O
Problem, con’t
O
HCCH2CH3
nucleophile
+
O
HCCH3
electrophile
O
OH
HCCH C-CH3
CH3 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 a-hydrogens with
another aldehyde or ketone without a-hydrogens.
Commonly used carbonyl compouds without ahydrogens
O
O
O
HCH HCPh HCC(Me)
3
Of course, these will serve as electrophilic centers
Examples
Trick is to add compound with a-hydrogen to basic solution
containing the compound without a-hydrogen.
O
HCCH2 CH2CH3
O
+
HCPh
OH-
O
OH
HCCH CHPh
CH2CH3
Problem
Can the following compound be prepared in good yield by
an aldol condensation?
HO
HO
O
H
C
H2
H
O
C
Me H2
Me
O
H
Ph
Aldol Cyclizations
O
R
O
H
R
R
R'
OH_
O
1,4-diketone
Please do problem 22-30
OH
R-
OH
OH_
R-
Example 1
Possible sites of deprotonation =
O
O
O
B
A
CH3
CH3
OH
O
Site A to C=O leads to 4-membered ring
Site B to C=O leads to 6-membered ring FAVORED
EXAMPLE -2
A
Me
C
D
OH
O
O
O
B
Me
D to C=O give 6-membered ring
O
Example 3
O
O
O
HO
H
O
Example Starting diketone?
Show the diketone that would give the following
O
O
2H
O
O
CH3
Claisen Condensation
IMPORTANT POINTS
1. PKA OF ALPHA H’S ON ESTER ARE AROUND 24
(RECALL KETONES ARE AROUND 20.
2. THIS REQUIRES THE USE OF A SLIGHTLY
STRONGER 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 Condensations
Involves Esters with Alpha
Hydrogens
O
R-CH2C OR'
O
R'OC-CH-R
O-
O
R-CH2C OR'
O
R-CH2C
R'OC-CH-R
R'OC-CH-R
b-keto ester
O