Problem_Set_8__solution - Chem 3580 Spring 2009 Problem Set...

Chem 3580 - Spring 2009
Problem Set 8 - solutions
1. (a) Retrosynthesis
O
CH
3
O
CH
3
O
O
CH
3
O
O OH
!
O
CH
3
O
O OEt
!
"
O
O OEt
O
CH
3
+
!
"
intramolecular
aldol
Decarboxylation Hydrolysis
Michael
addition
Ethyl acetoacetate
Claisen
CH
3
OC
2
H
5
O
2
Forward synthesis
CH
3
O
O
2
NaOEt (1 equiv)
O
O O
Claisen
CH
3
O
CH
3
O
O
O
O
CH
3
O
O
O
O
Decarboxylation
CH
3
O O
NaOH (cat), H
2
O
!
Intramolecular aldol
O
CH
3
Michael Addition
O CH
3
O
O
O
H
Hydrolysis
Ethyl acetate
can be done in one step (H
3
O + , Heat)
Na
+
H
3
O +
H
3
O
+
!
(b) Retrosynthesis
O
O
OH
O
O
O
O
O
O
O
+
Br
H
3
C O
O CH
3
O
O
decarboxylation
alkylation
hydrolysis
intra-molecular
Claisen
(Dieckmann)
Forward synthesis
H
3
C O
O CH
3
O
O
1. NaOEt (1 equiv)
Intramolecular
Claisen
O
O
O
CH
3 Br
O
O
CH
3
O
Alkylation of the
enolate
base hydrolysis
(saponification)
followed by mild
acidic work-up
O
O
H
O
!
Decarboxylation
O 1. NaOH, H
2
O, !
2. Dilute HCl, 25°C

2.
O
O
!
Br
O
EtO
O O
Ethyl acetoacetate
!