UNIVERSITY OF THE WEST INDIES- CAVE HILL CAMPUS SEMESTER 1, 2018-2019

CHEM2705 – INTERMEDIATE ORGANIC CHEMISTRY

CARBANION CHEMISTRY - TUTORIAL SHEET #9 ANSWERS

1. Draw the structure of the product you would expect to obtain by (self) Claisen condensation
of each of the following esters. If an ester does not undergo Claisen condensation, explain
why it does not.

O CO2Et
O
OEt
OCH3
O
no -hydrogens
hence no condensation

O O

OCH3

O O

2. Suggest a synthesis of each of the following -dicarbonyl compounds by Claisen or

Dieckmann condensations.

O O
O O O O
  O CH3 H3C
  OMe   CH3

NaOMe, MeOH NaOEt, EtOH

NaOEt, EtOH

O O O
+
+ O OMe O
 OEt  O CH3   OEt O
H3C  OMe
H3C CH3


3. Devise synthetic routes to the following compounds using diethyl malonate OR ethyl
acetoacetate and any other required reagents. Show all intermediates, reagents and
necessary conditions to receive full credit.

1
2
O O O O Br O O
+
NaOEt, EtOH  H3O
EtO CH3 EtO CH3 EtO CH3

ethyl acetoacetate 2 1

O O O
1
 2
HO CH3 CH3 methyl ketone

2 1
UNIVERSITY OF THE WEST INDIES- CAVE HILL CAMPUS SEMESTER 1, 2018-2019
CHEM2705 – INTERMEDIATE ORGANIC CHEMISTRY

1
Br
O O O O O O
NaOEt, EtOH 
EtO OEt EtO OEt EtO OEt

diethyl malonate 1H

O O O O
1. NaOEt, EtOH H3O+  
EtO OEt HO OH
2. Br 1
1 1
2 2

1
1 1. LAH, THF 1 O
O OH 
 +  PCC, CH2Cl2
2. H3O 2
2 2 H
OH H 1
1 1

O O O O 1 3 O O
2
NaOEt, EtOH  Br Br NaOEt, EtOH
EtO OEt EtO OEt EtO OEt

diethyl malonate 1
Br 3
2

O O O O O O
+
H3O 
EtO OEt EtO OEt HO OH
3 2 1 1 3
1 3
Br 2
2

O MeOH,  or O
1  CH2N2, Et2O 1 
OH OCH3
2 2
3 3
Ester can be made from
Carboxylic acid

1
Br
O O O O O O
NaOEt, EtOH 
H3C OEt H3C OEt H3C OEt
 H
ethyl acetoacetate 1
UNIVERSITY OF THE WEST INDIES- CAVE HILL CAMPUS SEMESTER 1, 2018-2019
CHEM2705 – INTERMEDIATE ORGANIC CHEMISTRY

O O 2 O O
1. NaOEt, EtOH 1 Br +
3  H3O
H3C OEt H3C OEt
1 1
1
2

O OH
O O 1. LAH, THF 1
1 
  2. H3O+ CH3
H3C OH  CH3
1 1 2 1
2 1
2
3 3

4. Give the major organic product(s) for each of the following reactions or reaction sequences.

O O O O
 1. NaOEt, EtOH 
CH2CH3  OCH2CH3 
i +
+
2. H3O CH3

O O
H3C H3C 
 OCH2CH3 1. NaOEt, EtOH 
ii CH3
2. H3O+ O
O

O OH

5% NaOEt, EtOH 
 H 
iii + N
 CN


CN

O O 1. NaOEt, EtOH O O
iv 
OCH2CH3 2. H3O+,  OCH2CH3

+

H3C CH3
CH3

H3C Br O CH3

CH3
 UNIVERSITY OF THE WEST INDIES- CAVE HILL CAMPUS SEMESTER 1, 2018-2019
CHEM2705 – INTERMEDIATE ORGANIC CHEMISTRY

5. Draw the structures of the precursors to each of the following Michael reaction products.
Label the Michael donor and the Michael acceptor in each case and formulate the reaction.

CO2Et O
O O O
  CH2CH2CCH3
   

  O
CH2NO2 O

NaOH NaOH NaOEt

EtOH EtOH EtOH

CO2Et O
O O O

CH3NO2 ACCEPTOR
O
DONOR O
ACCEPTOR ACCEPTOR
DONOR DONOR

6. Write the expected major outcome of the following carbonyl compound with each of the
reagents (a)-(g). Assume a workup at the end of the b, e, f, and g.

CH3

H3C H
O
O
acetal formation CH3

+
a. HOCH2CH2OH, H
H3C H
HO H primary alcohol

b. LiAlH4, Et2O
g. (CH3CH2CH2CH2)2CuLi Assuming aq. workup
CH3 CH3
followed by treatment with CH3
H3CH2CH2CH2C Cl
CH2=CHCH2Cl in THF c. Cl2, CCl4
CH2CH=CH2 Cl
H3C H H3C H
H3C H trans dihalide
O O
O

+
f. (CH3CH2CH2CH2)2CuLi, THF d. KCN, H , HCN

Assuming aq. workup

e. CH3Li, Et2O cyanohydrin CH
3
cuprates undergo conjugate addition
CH3
H3CH2CH2CH2C Assuming aq. workup CH3 H3C H
H
HO CN
H3C H
O H3C CH3 Conjugate addition was accepted
HO H as well.
UNIVERSITY OF THE WEST INDIES- CAVE HILL CAMPUS SEMESTER 1, 2018-2019
CHEM2705 – INTERMEDIATE ORGANIC CHEMISTRY

7. Propose syntheses of the following compounds using Robinson annulation reaction using a
retrosynthetic approach. Draw the structures of both reactants and the structure of the
intermediate Michael addition product in each case.

O
O O

O EtO2C
CO2Me CH3
CH3
Michael Reaction

O O O O
   
    
  

O   O O O O O
H OH H
CH3 CH3 CH3 CH3
Acceptor Donor
Aldol Condensation

1. NaOEt, EtOH
2. NaOH, EtOH, 

Aldol Condensation

H  
  O
 
HO  O O O
O O

    
  

CO2Me 
MeO2C  MeO2C  MeO2C
Donor Acceptor

Michael Reaction
1. NaOMe, MeOH
2. NaOH, EtOH, 

Aldol Condensation

H 
 HO   O  O  O O
 O O
  
   
   CO2Et
 
EtO2C 
EtO2C
EtO2C
CH3 CH3 Donor Acceptor

Michael Reaction
1. NaOEt, EtOH
2. NaOH, EtOH, 
UNIVERSITY OF THE WEST INDIES- CAVE HILL CAMPUS SEMESTER 1, 2018-2019
CHEM2705 – INTERMEDIATE ORGANIC CHEMISTRY

8. Propose a detailed mechanism for the following transformation. Use curved arrows to show
movement of electron pairs and be sure to draw structures of all important reaction
intermediates.

OH
H NaOH, EtOH, 
OCH3 OCH3
+
O
O O
CH3
CH3
ROBINSON ANNULATION
H-OEt

OCH3 OCH3 OCH3

O O O O O
H H
CH3 CH3

OCH3 OCH3 OCH3

O O O O O
H O
CH3 CH3 CH3
H-OEt

HO

OCH3 OCH3 OCH3

O O O
OH
H CH OH CH3 CH3
3
HO

9. Suggest mechanisms for the following reactions. Highlight why the number of equivalents of
Grignard reagent (EtMgI) used is important in each case.

O Et MgBr
OH
O 1. 2 equ. EtMgI, THF
i. OH
2. H3O+
1st equivalent acts as 2nd equivalent acts as
a nucleophile and a nucleophile and H3O+
attacks lactone to attacks the ketone to
generate a ketone. form a tertiary alcohol.

O MgBr O Et MgBr O MgBr

Et
O Et Et
Et
O O
MgBr MgBr
UNIVERSITY OF THE WEST INDIES- CAVE HILL CAMPUS SEMESTER 1, 2018-2019
CHEM2705 – INTERMEDIATE ORGANIC CHEMISTRY

O OH
1. 2 equ. EtMgI, THF
ii. H
2. H3O+ H
O
H HO2C
O
1st equivalent acts as a base
Et MgBr
and is quenched by carboxylic +
acid group H3O

O O MgBr
Et MgBr
H
H
O O
2nd equivalent acts as a
MgBr MgBr
O nucleophile and reacts with O
aldehyde to make an alkoxide
Both anions quenched in workup

10. Predict the products or reactants for the following reactions. Assume the Grignard to be in
excess in part d. and assume a workup occurs in part e.

a. Br PPh3 PPh3
Br

BuLi
b. PPh3 I PPh3 PPh3

O Ph3P=CH2
c.

WITTIG MECHANISM

Ph3P=CH2
O

Ph3P-CH2 -Ph3P=O

O O
PPh3
PPh3
UNIVERSITY OF THE WEST INDIES- CAVE HILL CAMPUS SEMESTER 1, 2018-2019
CHEM2705 – INTERMEDIATE ORGANIC CHEMISTRY

O OH
+
d. MgBr + then H3O
H OCH3 H

Me Cl Me CH3
(CH3)2CuLi
e. O o O
THF, -78 C

11. Specify the missing reactants of major products in each of the following reactions. Be very
careful to specify stereochemistry where necessary.

O O

a. +

O O

O O
H

b. + O O

O H O

c. 
+ H
CN
CN

CO2Et CO2Et
d. + 

CO2Et CO2Et

12. Show how each of the following molecules might be synthesized by Mannich reactions.
(Hint: Work backward, identifying the bond made in the Mannich reaction)

O H H O
1. HCl, EtOH
2. NaOH, H2O H
N O HN
+ +
O H O
UNIVERSITY OF THE WEST INDIES- CAVE HILL CAMPUS SEMESTER 1, 2018-2019
CHEM2705 – INTERMEDIATE ORGANIC CHEMISTRY

O H CH3 1. HCl, EtOH

2. NaOH, H2O O H3C
HN
N + O +
H