Download Biehl PPT Part2

Synthesis of Ketones From Acids
RCOOH
+
LiOH
RCOO- Li+ + R’- Li+
Dry
THF
Dry
RCOO- Li+
OLi
R
THF
OLi
R'
DIANION
IMPORTANT: NO WATER TO HERE
OLi
R
R
OLi
R'
OH
HOH
H+
O
OH
R'
GEM DIOL
R
R'
Example of Ketone from Acid
O
OH
LiOH
O
OLi
THF
CH=CH-Li
OLI
O
HOH
CH=CH2
H+
OLi
CH=CH2
Synthesis Using Acid and RLi
Convert PhEt to Cyclopropyl ethyl ketone
KMnO4
HOT
1. LiOH
O
OH
How could one prepared benzoic acid
From ethyl benzene?
Side-chain oxidation!!!!
Appears as if we could
start with benzoic acid
and introduce ethyl
group by EtLi.
2. EtLi
3. HOH
H+
O
Et
Synthesis of Aldehydes and
Ketones from Acid Chlorides
1. Preparation of acid chlorides
O
O
SOCl2
R
OH
R
Cl
R = almost anything!! H, Alkyl, Aryl, etc
2. Preparation of aldehydes - bulky reducing reagents
O
O
AlH(Ot-But)
3
R
Cl
R
Reduction to ROH does
H not occur - steric
Synthesis of Ketones
Recall that ketones react with acid chlorides to give alcohols.
O
R
O
R'Li
Cl
R
OH
R'Li
R'
R'
R
R'
OLi
R
Cl
R'
TO STOP AT KETONE STAGE, NEED A
MILDER ORGANOLITHIUM
USE OF ORGANO CUPRATES
Rli + CuI --------> R2CuLi
O
R
Cu +
R
R'
O
Cl
R
R'
STOPS: addition to acid
chloride is much faster
than addition to ketone.
Example
O
Cl
Cl
CuLi
2
CuLi
2
O
Reactions of Carbonyls
Nucleophilic addition - pages 797-800
Base-promoted additions
Nucleophilic anion attacks C=O to give alkoxide
which is neutralized to alcohol by acidic work-up.
Acid-catalyzed additions
O
+
+H
+
O
+
H
Nu-
O
NuCOH
H
increases electrophilicity of carbonyl group
Relative rate of addition: HCHO > RCHO> RCOR
WITTIG REACTION
R
R
O
+
R'
Ph
: C P Ph
R'
Ph
Wittig reagent
R
R
C C
R'
R'
+ Ph3P-O