from chapter(s) in the recommended text Reactions Of Ester... · Reactions Of Ester Enolates With...
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©Kevin Burgess, April 14, 2020 1 Reactions Of Ester Enolates With Esters from chapter(s) _____ in the recommended text A. Introduction
Transcript of from chapter(s) in the recommended text Reactions Of Ester... · Reactions Of Ester Enolates With...
©Kevin Burgess, April 14, 2020 1
Reactions Of Ester Enolates With Esters from chapter(s) _____ in the recommended text
A. Introduction
©Kevin Burgess, April 14, 2020 2
B. Enolates With Ester Electrophiles (Claisen Condensations) Homocoupling Of Esters
enolates with esters.
more stiochiometric. transesterification.
OMe
O
OMe
OH
PhOMe
O-
OEt
O
OEt
O-
O-
OtBu
electrophile nucleophile electrophilenucleophile nucleophile nucleophile
ethyl acetate
EtO-
enolate
EtO
O
tetrahedral intermediate
-EtO-
OEt
O
HOEt
O-
EtO
O
OEt
O
EtOO-
1,3-dicarbonyl
EtO-
enolate
O
OEt
O
H
O
OEt
O-
©Kevin Burgess, April 14, 2020 3
Ph OMe
O
(i) MeO-
(ii) H+
1,3-dicarbonyl
OMe
O
Ph
PhO
OEt
O (i) EtO-
(ii) H+ OEt
O
O
O
O (i) -OCH2CHCH2
(ii) H+O
OO
OEt
O O
OMe
O O
OEt
O
OMe
O
©Kevin Burgess, April 14, 2020 4
Uncontrolled Cross-Claisen Condensations
Controlled Cross-Claisen Condensations
only one
OEt
O (i) EtO-
(ii) H++OEt
O
+ +OEt
O
OEt
OO O
constitutional isomers
+OEt
OO
OEt
OO
OEt
O
OEt
O
Ph OEt
O
Ph OMe
O
OMe
OCl
OMe
O
MeO OMe
O
OMe
OPh
enolate 1 enolate 2 enolate 3
OEt
O-
OEt
O-
OMe
O-
Ph
OEt
O (i) EtO-
(ii) H++
OEt
OA
OEt
O (i) EtO-
(ii) H++
Ph OEt
OB
©Kevin Burgess, April 14, 2020 5
OMe
O (i) MeO-
(ii) H++
Ph OMe
OC
OMe
O (i) MeO-
(ii) H++
OMe
OD
Cl
MeO OMe
O
OMe
O+
(i) MeO-
(ii) H+E
OMe
O (i) MeO-
(ii) H+F+
OMe
O
Cl
Ph
letter ______ letter ______ letter ______
OEt
O
B
Ph
O
OMe
O
D
O
OMe
O
E
MeO
O
EtO OEt
O O+EtO
O
OEt OEt
O
Ph
O
CO2Me+Ph
O
OMe MeO
O
©Kevin Burgess, April 14, 2020 6
Intramolecular Reactions Of Ester Enolates With Esters (Dieckmann Reactions)
enolate
MeOOMe
O
O
MeO-
form enolatehere
enolate in conformation for cyclization
MeOOMe
O-
O
OMe-O
OMe
O
a cyclopentanone
-MeO-O
OMe
O
-MeO-CO2Me
O
-MeO-
OMe
O
CO2Me
O
O
O
CO2Me
©Kevin Burgess, April 14, 2020 7
form a single point of contact between two rings.
more than one less diminished in
-MeO-MeO OMe
O O
MeO
O O
-MeO-
O
OMe
CO2Me
+
CO2MeO
OMe
O
O
-nPrO-
O
OnPrCO2nPr
+OnPr
O
O
CO2nPrO
©Kevin Burgess, April 14, 2020 8
the same configurations.
C. Decarboxylation Of 3-Oxocarboxylic Acids From Carboxylates
-iPrO-
CO2iPr
CO2iPrCO2iPr
+
assume trans-fused 6,5-rings are not formed since they are less stable
CO2iPriPrO2C
O
iPrO2C
CO2iPr
O
-MeO-MeO OMe
O O
+OMe
OO
MeO
O OR
R R
O O-
O
-O
O
O+
©Kevin Burgess, April 14, 2020 9
O
O-
O
-CO2-CO2O
O
O-
O
O-
O
O-
O
O-
OOO
-O-CO2-CO2
O-O-
O-
O O-O2C
O
-CO2-CO2O-
O-
O-
O
Ph
NN+
-O
O
O-
O-CO2-CO2
Ph
-NN-O
O-
©Kevin Burgess, April 14, 2020 10
From Carboxylic Acids carboxylates and carboxylic acids enols (whereas carboxylates produced enolates).
O
OO OO
O+
H H
-CO2
O
O
O
O
O
O
-CO2
H
H
OH
OH
O
O O
CO2HO
H
-CO2 -CO2OH
OH
O
O
Ph
NN+
-O
O
O
OH H
-CO2 -CO2
Ph
HNN-O
OH
©Kevin Burgess, April 14, 2020 11
D. Classical Syntheses Of Amino Acids
racemates.
OOH
O
NH3, NaBH4
amino acid ____valine______
NH2OH
O
HO
O NH4Cl/KCN
H2O
H3O+
amino acid tyrosine
HO
NH2
CN HO
NH2
COOH
O ONHAc
O O
(i) NaOMe, MeOH
(ii) Br
H3O+
heat
amino acid leucine
O O
O O
NHAc NH2
O
OH
Ph OH
O
Br
(i) Br2, PBr3
(ii) H2O
excess NH3
amino acid phenylalanine
Ph OH
O
Ph OH
O
NH2
©Kevin Burgess, April 14, 2020 12
Et O O EtNHAc
O O
(i) NaOMe, MeOH
(ii) Br Ph
H3O+
heatEt O O EtO O
NHAc NH2
O
OHPh
Ph
OH
O
Br
(i) Br2, PBr3
(ii) H2O
excess NH3OH
O
OH
O
NH2
O2NCO2H
O
H2, Pd/C
NH
O
OH
©Kevin Burgess, April 14, 2020 13
E. Thioesters Are More Reactive Than Esters stronger better milder
huge better Nature’s Equivalent To Claisen Condensations
coenzyme A or CoASH
HS NH
NH
OO O
OH
P OO
O-PO
O-O
O N
N
N
N
NH2
OHOPO
O--O
acyl coenzyme A or acyl-CoA
S NH
NH
OO O
OH
P OO
O-PO
O-O
O N
N
N
N
NH2
OHOPO
O--O
O
transthioesterificationproduct
-SR -CO2HO SCoA
O O
malonyl-CoA enolate of thioester
HO SR
O O
SR
O-
©Kevin Burgess, April 14, 2020 14
product
SR
O
SR
O O
-SR
SR
O
-O SR
O O+
-CO2O
SR
O
ketonereduction
showSi-face addition
of hydride
dehydration
-H2O
OH
SR
O
SR
O
hydrogenation
+H2SR
O
