Chemistry 6941, Fall 2007 Synthesis Problems I - Key Dr.

Peter Norris

1. Show retrosynthetic analyses for each of the following molecules that go back only to the starting
materials given below. Then give an efficient synthesis of each molecule showing the products
formed in each step. Assume that you have access to any of the usual reagents such as Br2, AlCl3,
Fe, HBr, HNO3, H2SO4, etc.
a. Retrosynthesis

OH OH O
Li
H

Br

Synthesis

Br2, heat Br 2 Li, ether Li

O
H

OH OLi
H 3O+

b.
Retrosynthesis

OH OH
O
Li

Br

Synthesis

Br 2, Fe Br 2 Li, ether Li

OH OLi
+
H3O
c.
Retrosynthesis

OH OH O
Li
H

Br

Synthesis

Br 2, Heat Br 2 Li, ether Li

O
H

OH OLi
H 3O +

d.
Retrosynthesis

OH OH O

MgBr

Br O

Synthesis Cl
O OMgBr
CH 3COCl MgBr

AlCl3 ether
H3 O+

Mg OH
Br MgBr
ether
 e.
Retrosynthesis

OH OH O
O2 N O2 N O2 N

MgBr

O
O

Cl
Br
Synthesis
O O
CH 3COCl HNO3 O2 N

AlCl3 H 2SO 4

CH 3Cl AlCl3

CH 3
Br2 Br Mg MgBr ether
heat ether

OH BrMgO
O 2N H 3O+ O 2N

2. Give structures of the products from each step within the following “roadmap” and match the
spectral data to the product.

Br 2 , heat Br Mg, ether MgBr H

O Na 2Cr2 O7 OH OMgBr
H 3O +

H2 SO4
H 2O

( 13 C 200 ppm) (IR 3300 cm-1)

a.
1. Br 2 , heat Br Li LiO HO Br
2. 2 Li, ether
1. 2. 3. 4. 5.
3. CH 3CHO

4. H 3O +
5. HBr

b.
1. CH 3COCl, AlCl3 O O Al OH ONa O
2. LiAlH4 , ether 2. 3.
1. 4. 5.
3. H3 O+ Li+
4. NaH, ether
5. CH 3CH2 Br 4

c.
1. NaBH 4, CH 3OH LiO HO
O 2. HBr OH Br Li
3. 2 Li, ether 1. 2. 3. 4. 5.

4. CH3 CH 2CHO
5. H 3O+

d.

1. H 2SO 4, H2 O
2. Na2 Cr 2 O7, H2 SO4 OH O Ph Ph
OMgBr OH
3. PhMgBr, ether 1. 2. 3. 4.

4. H 3O+
5. NaH, ether
6. CH3 CH 2CH 2Br Ph Ph
ONa O
5. 6.

e.
1. PDC, CH 2Cl2 Ph Ph
OH H O OLi OH O OMgBr OH
2. CH3 Li, ether
1. 2. 3. 4. 5. 6.
3. H 3O +
4. Na 2Cr 2O7 , H 2SO 4
5. PhMgBr, ether
6. H3 O+

f.
1. CH 3COCl, AlCl3
O O OH ONa O
2. HNO3 , H2 SO4
3. NaBH 4, CH 3 OH 1. 2. 3. 4. 5.

4. NaH, ether
5. CH3 CH 2 CH 2Br NO2 NO 2 NO2 NO 2
4. Design syntheses of the following molecules using only the sources of carbon shown below. Again,
assume that you have access to all of the common inorganic reagents (Br2, AlCl3, Fe, HBr, etc.).

a.
Design (Retrosynthesis)

O
O
HO
Cl

NH2

Br HO
+ OH
O OH

NH2 NH 2 NO2

HO Br Li
O O + OH OH

NO 2 NO2 NO2 NO2

O
O
+
Cl

Construction (Synthesis)

HBr 2 Li
HO Br Li
ether
O O
O
Cl HNO 3
ether
AlCl3 H2 SO4
NO2

O O ONa OH

Sn Br NaH

HCl ether
NH 2 NO 2 NO2 NO2
b.
Design (Retrosynthesis)

HO OH
OH

HO HO
O HO

OH Br Li

OH H
MgBr
O

Br

Construction (Synthesis)

HBr 2 Li
OH Br Li
Br 2 ether
heat
Br
OH PDC O
Mg ether
CH 2Cl2
ether H
MgBr

PDC H 3O +
ether
CH2 Cl2
O HO LiO

BrMgO H 3 O+ HO
c.
Design (Retrosynthesis)

O
O
OH
OCH 3
CH3 Br

Br HO
O

OH O
+ CH 3MgBr CH 3 Br
H 3CO
3 o alcohol
(2 equiv. subst.)

Construction (Synthesis) O

Mg 0.5 OCH3 OMgBr

HO
H 3O+
HBr

O Br ONa NaH OH
ether

d.
Design (Retrosynthesis - several ways to do this one)

Br H H

Li Br
O OH
OH OH
d. (cont’d.)

OH
Br Li

O OH OH O

H H H H H

Li Br

Construction (Synthesis)
Br Br Br
Br2 Br 2 Br2

heat heat Fe

2 Li ether 2 Li ether 2 Li ether

Li Li Li

O
ether
Li H H

OLi O OH OLi
PCC H 3O +
H H H
ether CH 2Cl2

H 3 O+
Li
OH O
PCC

CH 2Cl2 ether OLi

H 3O +

HBr
Br OH
e.
Design (Retrosynthesis)

OH
CH3 CH 2 OH

OH OH Li Br

Li Br HO

H OH
OH
OH O

Construction (Synthesis) Br Li

HBr 2 Li Br 2 2 Li
HO Br Li
ether Fe ether

OH H
PCC Li H 3O +
O ether OLi OH
CH2Cl2 (quench)

dil. H 2SO4
Li
(E1 )
OLi m-CPBA
O
ether CH2 Cl2
"steric contr ol"
(E/Z) isomers
H 3 O+ (quench)

OH major product :
dil. H 2SO4 tetrasubstituted
(E ) isomer, alkene
(E1 ) conjugated with ring