Exam 4 – Extra Problems – Key
Br
1.
O
H
OH
O
O
O O
2.
EtO
H
+
EtO
O
OEt +
Me
O O
EtO
OEt
OEt
+H
O
EtO
O
O O OEt
EtO
OEt
H
OEt
O
O O
O O H
+ OEt
O
O
EtO
O
H3O
O
CO2
+ H2O
O
A
O O
OEt
OH
Br
O
O
EtO
OEt + OH
O O
EtO
H
Br
+ H2O
O O
1. HO
+
O
2. H3O+
B
EtO
O
Figures by MIT OCW.
1
3.
NaCN
OEt
(a)
dil. HOAc
N C
O
dil. HOAc
4.
H
H3O
HO
C N
EtO
H3O
CH3 O
OH
HO
D
CH3
CH3 O
O
B
3
OMe
1 2
5
OMe
4
O
O
O
O
O
O
OMe
5
B H
5
4 3
1 2
OMe
O
O
Me
OH
O
CH3
O
OEt
D
NaCN
EtO
O
CH3
O
(b)
H O
O
Figures by MIT OCW.
2
Massachusetts Institute of Technology
5.13: Organic Chemistry II
5.
OH
H
O
OTs
O
OH2
D
H
H
H
H
Figures by MIT OCW.
In this "Pinacol- like" concerted process, the migrating bond must be antiperiplanar
to the LG so that the oxygen can stabilize the developing change in the TS.
OTs
HO
H
HO
d+
dOTs
H
Figures by MIT OCW.
Only the ring fusion bond is a.p.p. to the LG.
H OTs
D
OH2
H
OH
O
O
Figures by MIT OCW.
This Grob fragmentation is also concerted, so the bond that is cleared must be antiperiplanar
to the LG.(only the fusion bond is a.p.p.)
dOTs
OTs
H
d
OH
+
+
d OH
H
Figures by MIT OCW.
Only the bond a.p.p. to the LG is involved in these processes. The position of the oxygen determines
which product will be formed.
Figures by MIT OCW.
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5.13: Organic Chemistry II
6.
O
CF3
H
OMe
O
OMe
H2O
HO
OMe
OMe
OMe
H2O
H
OMe
7. Each of these mechanisms proceeds through an oxime.
O
R
Me
H
O
H
Me
HO
H2O
OH
R
Me
OH
N
H2
R
Me
PT
R
N
H
NH2OH
OH
H2O
N
R
H
R
Me
OH
N
Me
Would likely form mixture of
OH
N
R
HO
and
Me
R
N
Me
(Cont.)
Figures by MIT OCW.
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Massachusetts Institute of Technology
5.13: Organic Chemistry II
7. Cont.......
N
O
N
OH
PCl5
Ar
PCl5
N
C
Me
Ar
Me
O
Me
O
(The substituted alkyl
group can migrate)
N
H
N
Me
Ar
PT
Ar
N
C
H2O
Me
OH2
OH
H
N
Me
Ar
Ar
OH2
Me
H
N
Ar
Me
O
O H
H
N
O
O
Me
O
... The methyl group can also migrate.
Me
as before
Cl5P
Ar
O
OH2
N
N
Ar
Me
OH2
Me
N
Ar
as before
O
O
O
Me
N
H
Figures by MIT OCW.
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Massachusetts Institute of Technology
5.13: Organic Chemistry II
7. Continued. The nitrilium ion formed after migration is very electropholic. the aryl group
is electron-rich --> electropholic aromatic substitution.
as before
O
O
O
N
O
C
H2O
H
N
Me
Me
O
N
O
Me
8.a) Both of the substitution reactions must go through a a cationic species. Formation of this
intermediate is the RDS. In the first reaction, the oxygen can facilitate ionization by donating its
lone pair into the C-LG antibonding orbital. This speeds up the reaction . (NGP!)
O
X
O
d+
(s * c-x)
H
dOSO2Ar
O
Figures by MIT OCW.
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Massachusetts Institute of Technology
5.13: Organic Chemistry II
In the second reaction neighbouring group participation is not possible because there is no
overlap between the oxygen lone pair s *cx. The ionization step is slower.
RDS
KDS
O
O
no
KD
Overlap
Overlap
O
O
H
H
H
H
OSO
OdO2Ar
Ar
X
X
2
b) Both rxns proceed through the following intermediate A. the acetate ion can attack two
possible sites to give the two observed products.
O
OAc
(a)
O
(a)
O
OSO2Ar
D
O
(b)
D
O
H
D
O
O
(b)
O
OAc
D
The rxns essentially proceed through an " SN2 - like" pathway because of the NGP.
--> No other stereoisoness are formed.
Figures by MIT OCW.
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Massachusetts Institute of Technology
5.13: Organic Chemistry II
O H
9.
NH2
HO
H2
N
Me HO
H
Me
HO
HO
OH
PT
H
N
HO
OH2
HO
N
HO
Me
HO
H
Me
HO
HO
NH
HO
H
NH
HO
Me
Me
H2O
10.
O
H
OMe
Me
OH
OMe
O
O
H
OMe
Me
OH2
OMe
O
OMe
O
OMe
O
OMe
C
Me
OMe
OMe
O
OMe
O OMe
Me
OMe
This carbon more nucleophilic
because cation formed stabilized
by OMe & Me & not destabilized
by orthoacyl group.
(cont. on next page)
8
Figures by MIT OCW.
Massachusetts Institute of Technology
5.13: Organic Chemistry II
10. (cont......)
OMe
O
O
OMe
Me
OMe
O
O
C
Me
O
OMe
Me
OMe
This species cannot aromatize,
but it can open up again to form
a more stable acylium ion. (Stabilized
by other oxygen)
O
OMe
C
OMe
Me
O
This intermediate can re-form
the 5-mem. ring intermediate
or close to the six-membered
ring.
OMe
O
OMe
Me
OMe
This one can lose H
aromatize.
O
to
H
OMe
H2O
O
OMe
Me
OMe
O
OMe
Figures by MIT OCW.
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Massachusetts Institute of Technology
5.13: Organic Chemistry II
11.
O OMe
O
(a)
O
OMe
(1 eqvn)
O
O
OMe
O
Ph
OMe
Ph
O
Ph
Ph
O
O
O
Ph
Ph
O
O
(b)
O
OH
O
OH
H
O
H O
O
OMe
H
OH
O
HO
H O
HO
O
12.
O
O
(a)
Na2Cr2O7
Ph
O
Na2Cr2O7
OH
OH
Ph
OH
O
CH2N2 or
MeOH, H+
Ph
OMe
+
O
CH2N2 or
OH
MeOH, H+
OMe
2. H
O
1. OMe
1 eq.
O
Ph
2. MeI
OMe
OH
O
1. 1 eq. OMe
O
Ph
OMe
2. MeI
O
Ph
O
OMe
O
O
PCC
(b)
1. LDA, H
Ph
O
2. OH cat. H2O
Ph
OH
Ph
O
PCC
Ph
H
10
Figures by MIT OCW.
13.
O
O
13
C
1 equiv
Me
OEt
OEt
O
O OEt
O
13
C Me
13
OEt
C OEt
O
OEt
H
OEt
Me
OEt
O
13
EtO
H
C
O
O
13
Me
EtO
C
O
O
OEt
O
13
Me
EtO
C
Me
O
13
EtO
OEt
OEt
H
C
O
OEt
Me
O
13
EtO
O
O
Me
C
13
H
EtO
O
Me
C
H
RO
O
14.
H
O
H OR
OR
Cat.
O
O
Me
O
Me
Me
Me
O
O
O
O
Me
H
OR
H
O
Me
RO
O
Me
O
O
O
Me
O
H
OR
Cat.
O
Me Me
+
RO
O
H
HO
O
Me
HO
Me O
O
OH
Me
O
Me
Me
Product 1
RO
RO
HO
O
H
H
O
Me
O
Me
Me
O
Me
HO O Me
Me
Me
10
11
+
Product 2
OH
Figures by MIT OCW.
Figures by MIT OCW.
15.
cat,
(a)
OH
O
O
O
"aldol" & "dehydration"
D
O
O
(1) LDA (1 equiv)
O
(2) O
1 eqvn
O
(b)
O
OMe
MeO
(1) OMe
(2) MeI
1 eqvn
O
O
MeO
O
(1) OMe
(2) MeI
OMe
O
MeO
OMe
O
LAH
OH
O
OH
O
H
(c)
O
Me
MeONa
OMe
O
Me
O
(1 eq)
Me
MeOH
OMe
LiAlH4
OH
OMe
H
OH
O
Me
+
,
O
O
Me
H ,D
O
K2CO3 (1 equiv)
MeBr
Me
Me
D
MeBr
O
O
H2
Pd/C
OMe
Me
Me
O
OMe
Me
O
O
Me
PBr3
MeOH
OH (cat)
OMe
MeOH
O
PCC
O
O
H+
OMe
H2O , D
Me
Me
Me
Figures by MIT OCW.
12
16.
O
O
O
O
H
OEt
O
O
EtO
OEt
OEt
O
O
O
O
O
O
O
O
OEt
OEt
H
O
O
H
O
OEt
EtO
EtO
EtO
OEt
O
O
O
EtO
EtO
EtO
OEt
OEt
O
EtO
EtO
OEt
O
OEt
O
O
O
EtO
EtO
EtO
O
EtO
OEt
OEt
O
OEt
OEt
EtO
O
EtO
O
O
H
O O
O
O
H
O
O
O
O
O
O
HO
HO
O
O
H
O
H2O
H
O
H
O
O
H2O
O
O
O
H
OH
O
O
O
H
O
O
O
O
O
H
HO
O
O
O
O
OEt
O
O
OEt
HO
O
O
OEt
Figures by MIT OCW.
13
O
O
H2O
HO
H
O
O
O
O
OEt
acid-cat.
hydrolysis
of ester
O
HO
H-O
Et
H
O
O
HO
O
OEt
OH
OEt
O
O
PT
EtO
OEt
O
O
O
H2O
EtO
H
EtO
OEt
H2O
OH
O
H
EtO
O
H
O
O
O
17
HO
A
H
H
O
O
OH
O
O
HO
HO
O
O
O
H
O
HO
H
O
O
OH
OH
OH
HO
H OH
H-OH
O
O
O
OH
B
HO H
HO
C
O
O
O
18
O
OMe
O
O
O
(+)
O
OMe
O OMe
O
O
OMe H
O
O
H OMe
MeO H
HO
O
O
OMe
H
HO
H OMe
O
O
H
H
H O
O
O
H OMe
OMe
O
O
O
Figures by MIT OCW.
14
19.
O
Me
O
H
O
OEt
H
OEt
O
O
O
O
O
O
H
O
Me
OEt
O
OEt
H
OEt
O
O
OH
H
OH
Me
OEt
EtO
O
OEt
Me
O
EtO
OEt
H 2C
O
O
Me
O
O
OEt
O
OEt
O
Me
O
Me
Me
O
OEt (1 eq.)
Me
H
O
OEt
OEt
O
OEt
Figures by MIT OCW.
15
20.
(a)
O OH
O
O
O
O
O
O
OH
O
OH
O
H
O
H
OH
O
O
(b)
O
O OMe
O
OMe
O
O
O
OMe
B
O
OH
O
OMe
O
O
O
OMe
C
(c) Carboxylate A generated from rapid deprotonation is not reactive toward nucleophilic attack by enolates. In
contrast, B can do further condensation generating C which can be deprotonated under rxn condition.
Figures by MIT OCW.
16
O
A
21.
O
O
Me
MeO
O
H 2N
Me
MeO
H
O
MeO
H
H
O
H
MeO
N
MeO
N
H2 O
H
O
MeO
OH2
MeO
N
N
N
H
H
MeO
O
N
OH
O
H
catalytic
OH
OH
Me
O
H
H
H2O
H2O
H
OH
H2O
O
O
O
MeO
H
MeO
O
MeO
MeO
N
N
MeO
N
N
H
H
OH2
H
N
O
H
H
H2 O
O
O
H
H3O+
O
H2O
O
(+)
MeO
MeO
O
H 2N
MeO
NH2
OH
H
N
H
Catalyst regenerated
Figures by MIT OCW.
17
OH
22.
O
O
O
H
OH
H
OH
Et
OH
OH
H
O
Et
O
O
O
Et
HO
Et
H
O
O
O
O
O
OH
Et
Et
O
O
OH
H Et
Figures by MIT OCW.
18
H
OH
23.
D
enantiopure
O
F3C
O
H
D
Cl
O
Cl
O
enantiopure
CF3
Note
inversion
Mechanisms
O
H
O
O
CF3
D
CF3
O
O
H
Cl
H
Cl
D
Cl
H
Neighboring group
participation avoids a high
energy carbocation
CF3
O
Sn2 backside attack
inverts the stereocenter
Cl
D
H
D
O
H
O
D
H
CF3
Cl
Figures by MIT OCW.
19
24.
Me
Me
H
OOH
O
OH
Me
Me
Mechanism:
H
Me
O
O
H
Me
O
O
H
Me
H
Me
Via phenonium ion
Me
O
Me
O
Me
Me
O
H
H
O
H
Me
Me
O
O
H
O
Me
Me
O
P.T.
H
H
H+
O
H
O
H
Figures by MIT OCW.
20
25.
O
Me
N
Me
O
Cl
H2O
D
Me
Me
O
N
O
H
O
Mechanism
O
Me
O
Cl
N
Me
Cl
N
Me
O
O
O
O
Me
Me
N
N
H
O
Me
H2O
O
H
O
Me
P.T.
O
O
Me
N
H
Me
O
P.T.
O
N
Me
O
H
O
Me
H
Me
H
O
N
HO
O
Me
Figures by MIT OCW.
21
26.
O
H
H2O, D
O
Me
H
Me
Me
Mechanism
O
H
O
H
OH
H
two steps
O
H
OH2
H
O
H
Figures by MIT OCW.
22
27.
OH
HCl
NH2
tBu
O
NaNO2
tBu
A
Mechanism:
OH
NH2
HO
N
O
H2O - N
O
N
O
Cl H
OH
OH
N OH
H
H
N
N
OH
H
N O
H N
H N
H
O
Note: Migrating group is
antiperiplanar to
Leaving group.
H
OH
OH
N
N
N
N OH2
H
O
H
O
H+
H
H
H
Next page for
B
Figures by MIT OCW.
23
# 27 Part B
tBu
Mechanism
OH
NaNO2
NH2
HCL
O
tBu
H
OH
(For diazonium Formation, see part A)
NH2
Once again:
The migrating group is
anti-periplaner to the leaving
group.
H
H
H
O
H
OH
H
N
N
H
H
O
O
tBu
H
Figures by MIT OCW.
24
H