Chemistry 213
Clark College
Homework 7: Enolates II SOLUTION
1. Predict the products for the following reactions:
O
O
a.
O
O
O
O
O
NaOEt
OEt
OEt
Ph
O
1) Ph2CuLi, -78°C
2) H2O
b.
O
O
O
O
O
O
O
c.
EtO
O
1) NaOEt,
O
OEt
O
O
HO
2) NaOH/H2O
3) HCl/H2O
4) Heat
O
O
NaOEt
H
O
d.
It can't ring close!
H
O
O
1) 0.99 eq LDA
e.
O
O
2)
3) H2O
O
f.
OEt
O
g.
O
H
h.
1) NaOEt
O
Br
2)
3) NaOH/H2O
4) HCl/H2O
5) !
O
1) NaOEt
H
O
O
O
Br
2) NaOEt
O
H
Br
H
O
O
NaOH
O
O
O
O
i.
O
Ph
O
NaOH
O
O
O
Ph
Ph
Homework 7
Spring 2008
Page 1 of 4
Chemistry 213
Clark College
2. The Claisen reaction. Determine the starting carbonyl compounds and reaction conditions that
would form the following Claisen reaction products.
initial attacked
enolate
ester
O
O
1) LDA
2)
O
EtO
EtO
3) H+EtO
O
O
For this crossed Claisen reaction,
LDA is used to completely form
one enolate, and a second ester is
brought in later to react with the
formed enolate.
O
EtO
O
O
NaOEt
Just a straightforward Claisen reaction
(self-condensation)
EtO
EtO
O
O
EtO 1 2
7
3
4
1) 1.01 eq
LDA
2) H3O+
6
5
O
O
EtO
A Dieckmann reaction
(intramolecular Claisen).
Judicious use of LDA gives
OEt the less-substituted enolate.
3. When 1,3-cyclohexanedione reacts with methyl vinyl ketone in the presence of sodium ethoxide, a
mixture of two isomeric products having the formula C10H12O2 are formed. Propose structures for
the two products and write the mechanism for their formation. (Hint: the products are formed
through Robinson annulations)
O
O
O
O
2a + 2b
NaOEt
O
O
O
2a
O
H
O
O
O
O
OEt
O
O
O
H
OH
O
H OEt
O
O
O
2b
O
H
OEt
O
O
O
OEt
O
O
O
H
OEt
O
O
H OEt
O
O
Homework 7
Spring 2008
Page 2 of 4
Chemistry 213
Clark College
4. Provide the structures of the starting aldehyde/ketone and the starting α,β-unsaturated carbonyl
compound that will form the desired Robinson annulation product when mixed with aqueous NaOH.
O
O
O
O
O
O
O
O
0.99 eq LDA is
a better base
choice here!
O
O
O
O
5. Compound 3 (C15H14O) is first treated with a slight excess of LDA and then with ethyl formate,
producing compound 4. Based on 1H-NMR datqa given for 3, propose structures for compounds 3
and 4.
O
3
1) 1.01 eq LDA
O
2)
H
O
4
O
H
OEt
1
H-NMR: 2.2 (s, 3H), 5.3 (s, 1H), 7.3 (multiplet, 10 H)
6. Compound 5 undergoes the four-step reaction sequence shown below, to form compound 6.
Based on the 1H-NMR data given for compound 6, propose structures for compounds 5 and 6.
1) NaOEt, xs
O
O
EtO
O
EtO
Compound 5
2) NaOH/H2O
3) HCl/H2O
4) !
Compound 6
Compound 6: (C9H18O) 1H-NMR: 0.7 (d, 6H), 1.2 (m, 1H), 1.4 (s, 9 H), 2.2 (d, 2H)
Homework 7
Spring 2008
Page 3 of 4
Chemistry 213
Clark College
7. Give the structures for products A – E in the following synthetic sequence. The formula of
compound E is given.
1) LDA
O
O
1) (CH3)2CuLi,
2) O
O
O
- 78°C
1) NaOEt
OEt
2) H2O
3) HCl/H2O
2) CH3I
A
B
O
OH
O
O
OH
O
1) NaBH4
2) H3O+
O
H+
C
D
E
C18H26O2
8. Perform the following syntheses.
O
O
EtO
OEt
1) NaOEt
2)
Br
OH
O
O
EtO
1) NaOEt
2)
OEt
Br
O
O
EtO
OEt
1) NaOH
2) H3O+
3) !
O
O
1) 2 eq CH3MgBr
2) H3O+
EtOH
H+
EtO
HO
You can't react a Grignard
directly with a carboxylic acid!
O
O
OEt
1) NaOEt
2) CH3Br
O
O
OEt
1) NaOEt
2)
Br
O
O
OEt
O
O
Ph
Homework 7
1) NaOH
2) H3O+
3) !
Spring 2008
1) 1.01 eq LDA
2) Br
Ph
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