D. J. Wardrop
Chem 232
[email protected]
Problem Set 6 Answers
Question 1.
Only five of the molecules below may be prepared as the sole product of allylic halogenation of the
respective alkene. Circle those five.
H3 C
H3C
Br
CH3
CH3
Br
CN
H3 C
Br
CH3
H2C
CH2
H3 C
Br
Br
H3C CH3
CH3
Br
(H3C)3C
H3C
Br
CH2
Br
CH2
Br
CH3
Br
CH2
CH3
H3 C
Question 2
Draw the major organic product in the boxes provided for each reaction scheme below. If the reaction is
regioselective, only draw the major product. Be sure to indicate the correct relative stereochemistry (i.e.
dashes & wedges or axial & equatorial bonds) where appropriate.
Na
O
OTs
O
H
THF
Me
Me
Ph
Br
O
O
H
Ph
NaN3
N3
O
O
THF
Ph
OMs O
O
An example of
Williamson ether
synthesis
Ph
NaCN
CN
O
O
Both reactions proceed
via SN2 mechanisms despite
the sterically hindered nature
of the C-atom undergoing
substitution. This occurs because
both leaving groups are at allylic
positions and the SN2 reaction
is favored.
MeCN
For each of the transformations shown above, by
what mechanism is product formed? (SN1, SN2, E1, or E2)
If the solvent was changed from THF to DMF would the
mechanism or rate of reaction change?
The use of DMF, a polar
non-protic solvent would
increase the nucleophilicity
of cyanide and increase the
rate of SN2 reaction.
Question 2 (contd.)
Which hydrogens
are more accesible?
KOt-Bu
OTf
THF
H
1,2-Elimination product
1,4-Elimination product
1,2-Addition
product
1,4-Addition
product
Br
heat
HBr
Thermodynamic
addition product
Br
25 °C
H
H
O
Br
heat
N Br
CHCl3
H
upon heating, NBS undergoes
decomposition to form Br2 which
mediates allylic bromination
O
HCl
-80 °C
Br
H
Kinetic,
Markovnikov
addition product
Question 3
Draw the major Diels-Alder adducts in the boxes provided for each reaction scheme below. If the
reaction is regioselective, only draw the major product. Be sure to indicate the correct relative
stereochemistry (i.e. dashes & wedges or axial & equatorial bonds) where appropriate.
heat
CO2Me
CO2Me
δ+
CO2Me
δ-
heat
MeO
OMe
CO2Me
Me
O
Me
H
heat
O
H
O
O
O
O
Me
H
H
O
O
heat
Me
H
O
O
Me
H
O
Me
H
O
H
O
O
H
O
this substrate pair
will react faster
since there is less
compression in TS
Which reaction will have the faster rate? Why?
CO2Me
endo-Diels-Alder
adduct resulting
from regioselective
[4+2] cycloaddition
H
O
Me
heat
O
O
Me
endo-Diels-Alder
adduct resulting
from [4+2]
cycloaddition
O
Me
CO2Me
O
Question 4
Devise a synthesis for each of the target molecules (products) below. Write the forward synthesis from
the reactant. Include all necessary conditions above/below the reaction arrow for each transformation.
Write out the product for each transformation in your synthesis separately.
O
Ph
O
Br2
Ph
Br
Br
CH2Cl2
O
2 x t-BuOK
THF
Ph
H
heat
H
CHO
O
O
Ph
O
Na+ -NH2
Ph
O
MeI
Ph
Me
H
not isolated
O
Na (metal)
Ph
Me
NH3 (l)
Na+ -NH2
MeI
O
O
O
H
Me
not isolated
H2
Pd-CaCO3
Me
lead acetate
quinoline
O
Ph
heat
MeO
H
CO2Me
O
Ph
MeO
O
Ph
H
heat
Ph
H
Ph
H
H2
Pd-C
O3
H
then
CO2Me Zn (metal)
H
CO2Me
OHC
MeO2C
CHO
Ph
Question 4 (contd.)
hydroboration occurs from
less hindered face
δ-
δ+
Et
Me
heat
t-BuO
H
H
BH3•THF
Et
then
CO2t-Bu H O , NaOH
2 2
O
H
H
H
HO
Me Et
H
CO2t-Bu
remember endo rule
Cl Cl
H
Cl2, hv
chlorine attacks allylic radical
from less hindered face at the
more substituted position
H
H
H
H
H
Cl
H
H
Why do you observe the relative stereochemistry in the product?
Question 5
Draw a reasonable arrow-pushing mechanism for each of the following transformations.
O
H
H
O
heat
NH
O
O
O
O
O
heat
NH
H O
O
H O
O
heat
Br
N Br
Ph
Ph
O
Why do you see regioselectivity in introduction of bromine atom?
Br2, H2O
Br
Br
OH
HO
Why do you see diastereoselectivity in the 1,4-addition product?
Question 6
The following product is not formed thermally, Why? What product would you expect instead using
FMO theory?.
[4+4] cycloadditions
are disallowed
heat
heat
[4+2] cycloadditions
are allowed
Question 7
Devise a synthesis for each of the target molecules (products) below. Write the forward synthesis from
the reactant. Include all necessary conditions above/below the reaction arrow for each transformation.
Write out the product for each transformation in your synthesis separately.
O
Ph
O
O
H
H
Ph
CO2Me
MeO2C
starting materials
product
Ph
Na, NH3
MeO
Diels-Alder cycloaddition
proceeds according to
the endo rule
O
O
Ph
O
H O
O
O
Me
H
Me
O
heat
Me
O
Me
O
then
H2O2, NaOH
Me
H
TsCl
H
Me
O
pyridine
TsO
O
H O
Me
intermediate
H
H
O
H
H
Me
NaN3
O
H
O
O
Me
O
O
Me
H O
O
O
O
O
H
H
Ph
CO2Me
H
Me
O
O
HO
O
H
starting materials
BH3•THF
O
H
HO
O
+
O
O
Ph
CO2Me
O
N3
O
Me
heat
OMe
O
Epoxidation occurs from
less hindered exo face
DMF
N3
H
Me
H
O
O
O
Me
H
Me
O