Organic Chemistry OnLine ©2000
© 2000, Paul R. YoungUniversity of Illinois at Chicago, All Rights Reserved
Conjugated Dienes &Cycloadditions
Organic Chemistry OnLine ©2000
CH3CH3
CH3
OH
Vitamin A: Retinol
A conjugated system consists of a series ofadjacent sp or sp2 centers such that there can
be overlap of -electrons.
Organic Chemistry OnLine ©2000
Vitamin A: Retinol
CH3CH3
CH3
OH
A conjugated system consists of a series ofadjacent sp or sp2 centers such that there can
be overlap of -electrons.
Organic Chemistry OnLine ©2000
Conjugated systems poses a series ofadjacent sp2 or sp centers
Simple Conjugated Systems
Organic Chemistry OnLine ©2000
Conjugated double bondsoverlap to form a
continuous system
Alkene p-orbitals overlapto form a system
Simple Conjugated Systems
Organic Chemistry OnLine ©2000
Conjugated double bondsoverlap to form a
continuous system
The overlap presents anenhanced barrier to
rotation around singlebonds in conjugated
systems.
Simple Conjugated Systems
Organic Chemistry OnLine ©2000
(CH3)3CO-
(CH3)3COH
Br
NBS
CCl4
Br
δ
δ
Synthesis of Conjugated Dienes
Organic Chemistry OnLine ©2000
Ionic Addition Reactions of ConjugatedDienes
+ HBr
Br
Br
1,2 addition
1,4 addition
12
3
4
Organic Chemistry OnLine ©2000
+ HBr
Br
Br
1,2 addition
1,4 addition
12
3
4
Ionic Addition Reactions of ConjugatedDienes
Organic Chemistry OnLine ©2000
Protonation on the terminal carbon generates the allylic carbocationwith cationic character on both carbons #1 and 3
1,4 addition
CH2
H
δδ
Br-
CH2
H
allylic carbocation
Br
CH2
H
+ HBr
Organic Chemistry OnLine ©2000
1,2 & 1,4 Ionic Addition Reactions ofConjugated Dienes
The 1,2- addition product forms rapidly at lowtemperatures.
Organic Chemistry OnLine ©2000
1,2 & 1,4 Ionic Addition Reactions ofConjugated Dienes
The 1,2- addition product forms rapidly at lowtemperatures.
The 1,4-addition product is predominant at highertemperatures.
Organic Chemistry OnLine ©2000
1,2 & 1,4 Ionic Addition Reactions ofConjugated Dienes
The 1,2- addition product forms rapidly at lowtemperatures.
The 1,4-addition product is predominant at highertemperatures.
Even at low temperatures, 1,4-addition products willpredominate if given enough time.
Organic Chemistry OnLine ©2000
1,2 & 1,4 Ionic Addition Reactions ofConjugated Dienes
The 1,2- addition product forms rapidly at lowtemperatures.
The 1,4-addition product is predominant at highertemperatures.
Even at low temperatures, 1,4-addition products willpredominate if given enough time.
The addition of HBr to butadiene is reversible and isolated1,2-addition product will convert to the 1,4-product athigher temperatures or at longer times.
Organic Chemistry OnLine ©2000
lower activation energy’faster reaction
high activation energy,slower reaction
Br
Br
Ene
rgy
Effect of Temperature and Time on ProductDistribution
Organic Chemistry OnLine ©2000
lower activation energy’faster reaction
high activation energy,slower reaction
Br
Br
Ene
rgy
Effect of Temperature and Time on ProductDistribution
Organic Chemistry OnLine ©2000
∆G˚ ∆G˚
Ene
rgy
Therefore, 1,2 addition isfaster, but forms a less stableproduct, while 1,4 addition is
slower, but gives a morestable product.
Effect of Temperature and Time on ProductDistribution
smaller ∆G˚, lessfavored at equilibrium,but formed faster
larger ∆G˚, morefavored at equilibrium,but formed more slowly
Br
Br
Organic Chemistry OnLine ©2000
∆G˚ ∆G˚
smaller ∆G˚, lessfavored at equilibrium,but formed faster
larger ∆G˚, morefavored at equilibrium,but formed more slowly
Br
Br
Ene
rgy
...at equilibrium (ThermodynamicControl) the more stable 1,4
addition product will be favored,but if you examine the initialproduct distribution, the more
rapidly formed 1,2 product willpredominate (Kinetic Control).
Effect of Temperature and Time on ProductDistribution
Organic Chemistry OnLine ©2000
Br
Br
H
H
3˚ carbocation initiallyformed; product also has
less steric hindrance
2˚ carbocation initiallyformed
Organic Chemistry OnLine ©2000
+heat
+heat
+heat
O
CH3
C
O
CH3
4 + 2 Cycloaddition Reactions
a diene... ...and adienophile
Organic Chemistry OnLine ©2000
4 + 2 Cycloaddition Reactions
a diene... ...and adienophile
+heat
+heat
+heat
O
CH3
C
O
CH3
Organic Chemistry OnLine ©2000
heat
O
CH3
C
O
CH3
a diene a dieneophile
Cycloaddition reactions work best with dienes containingelectron donating substituents and dienophiles containing
electron withdrawing substituents.
Organic Chemistry OnLine ©2000
s-cis s-trans
free rotation
s-cis stereochemistry is required for a4+2 cycloaddition reaction
Drawing the cyclohexene as a “chair” allows thestereochemistry of attached groups to be clearly described;the cyclohexene ring, however, is actually distorted due to
the 120˚ bond angles of the sp2 centers.
Organic Chemistry OnLine ©2000
Organic Chemistry OnLine ©2000
C
CH
HH
H
C
CH
CH
H
H
O
C
CH
CH
H
CH3
O
C
CH
CH
H
OCH3
O
C
C
H
H CO
C
O
O
C
CC
CH
H
C
O
C
O
H
H
C
CH
CH
H
NC
C
COOCH3
H
poor
Common Dienophiles
Organic Chemistry OnLine ©2000
H
H
H
H
H
H
H
H
H
H
H
H
...benzene can be formed from a 2+2+2 cycloaddition reaction
Organic Chemistry OnLine ©2000
O
O
H
H
H
CHO
H
CHO
Consider the reaction ofcyclopentadiene with
butanedial...
Organic Chemistry OnLine ©2000
O
O
H
H
H
CHO
H
CHO
Consider the reaction ofcyclopentadiene with
butanedial...
Organic Chemistry OnLine ©2000
With the carbonyl groupslined up underneath the
double bonds of the diene,there can be -
interactions between thediene and the electron
withdrawing groups onthe dienophile.
O
O
H
H
Organic Chemistry OnLine ©2000
CH3
CH3
HH
H
CHO
CH3
H
H H
OHCCH3
CH3 HH CH3
H
CHO
trans stereochemistry
CHO
H+
CH3
CH3
HH
CH3CH3H H
H
CHOrotate up
Organic Chemistry OnLine ©2000
+
CH3
HH3C
HCH3
HH3C
H
H HH3C CH3
H
H3C
H
H3C
rotate up H
H3C
CH3
H
cis stereochemistry
Organic Chemistry OnLine ©2000
cis trans
trans trans
H
H3C
CH3
H
CH3
HH3C
H+
CH3
CH3
HH
+
CHO
H
CH3
CH3
HH
H
CHO
1,4-trans
1,4-cis
14
14
Organic Chemistry OnLine ©2000
trans
cis
cis
trans
trans
trans
1,4- trans
1,4- cis
1,2- cis
1,2- trans
Organic Chemistry OnLine ©2000
HNC
H
NCH
CN
O
H
O
NH2
Suggest a synthesis foreach of the following
utilizing a 4 + 2cycloaddition reaction:
Organic Chemistry OnLine ©2000
H
O
CH3
O
O
HH
O
O
Suggest a synthesis foreach of the following
utilizing a 4 + 2cycloaddition reaction:
Organic Chemistry OnLine ©2000
H
Cl
H
H
O
CH3
O
H3C
H3C CH3
Suggest a synthesis for themolecule shown above utilizinga 4 + 2 cycloaddition reaction:
Organic Chemistry OnLine ©2000
H
Cl
H
H
O
CH3
O
H3C
H3C CH3
The molecule is a diketone, we can make ketones by:
Organic Chemistry OnLine ©2000
H
Cl
H
H
O
CH3
O
H3C
H3C CH3
The molecule is a diketone, we can make ketones by:
a) ozonolysis or oxidation of an alkene
Organic Chemistry OnLine ©2000
H
Cl
H
H
O
CH3
O
H3C
H3C CH3
The molecule is a diketone, we can make ketones by:
a) ozonolysis or oxidation of an alkeneb) hydration of an alkyne
Organic Chemistry OnLine ©2000
H
Cl
H
H
O
CH3
O
H3C
H3C CH3
The molecule is a diketone, we can make ketones by:
a) ozonolysis or oxidation of an alkeneb) hydration of an alkyne
Because ozonolysis will give us both carbonyls at once,that is our first choice.
Organic Chemistry OnLine ©2000
H
Cl
H
H
O
CH3
O
H3C
H3C CH3
The molecule is a diketone, we can make ketones by:
a) ozonolysis or oxidation of an alkeneb) hydration of an alkyne
Because ozonolysis will give us both carbonyls at once,that is our first choice.
12
3
45
6
Organic Chemistry OnLine ©2000
H3C
H3CCl
H
H
H3C
H
H3C
Suggest a synthesis for themolecule shown above utilizing a4 + 2 cycloaddition reaction:
Organic Chemistry OnLine ©2000
The molecule is a saturated alkyl halide, we must use acycloaddition reaction which will yield an alkene. We couldtherefore make this molecule by either:
H3C
H3CCl
H
H
H3C
H
H3C
Organic Chemistry OnLine ©2000
The molecule is a saturated alkyl halide, we must use acycloaddition reaction which will yield an alkene. We couldtherefore make this molecule by either:
H3C
H3CCl
H
H
H3C
H
H3C
a) reduction of an alkene
Organic Chemistry OnLine ©2000
The molecule is a saturated alkyl halide, we must use acycloaddition reaction which will yield an alkene. We couldtherefore make this molecule by either:
H3C
H3CCl
H
H
H3C
H
H3C
a) reduction of an alkeneb) addition of HCl to an alkene
Organic Chemistry OnLine ©2000
The molecule is a saturated alkyl halide, we must use acycloaddition reaction which will yield an alkene. We couldtherefore make this molecule by either:
H3C
H3CCl
H
H
H3C
H
H3C
a) reduction of an alkeneb) addition of HCl to an alkene
Because the double bond will form between the carbons ofthe diene, reduction of that double bond is our firstchoice.
Organic Chemistry OnLine ©2000
COOHHOOC
Br
Suggest a synthesis for themolecule shown above utilizing a4 + 2 cycloaddition reaction:
Organic Chemistry OnLine ©2000
The molecule is a dicarboxylic acid. The only way we knowto make carboxylic acids is by:
COOHHOOC
Br
Organic Chemistry OnLine ©2000
The molecule is a dicarboxylic acid. The only way we knowto make carboxylic acids is by:
COOHHOOC
Br
oxidation of an alkene
Organic Chemistry OnLine ©2000
oxidation of an alkene
COOHHOOC
Br
The molecule is a dicarboxylic acid. The only way we knowto make carboxylic acids is by:
Organic Chemistry OnLine ©2000
oxidation of an alkene
The molecule is a dicarboxylic acid. The only way we knowto make carboxylic acids is by:
CC
Br
HH
Organic Chemistry OnLine ©2000
H
H3CH
CN
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
Organic Chemistry OnLine ©2000
H
H3CH
CN+
CN
H3C
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
Organic Chemistry OnLine ©2000
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
CN
CN
Organic Chemistry OnLine ©2000
CN
CN
+
CN
CN
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
Organic Chemistry OnLine ©2000
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
CH3
HH
CN
H
CH3
H
H3C
Organic Chemistry OnLine ©2000
trans
cis
cis
trans
trans
trans
1,4- trans
1,4- cis
1,2- cis
1,2- trans
Organic Chemistry OnLine ©2000
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
CH3
HH
CN
H
CH3
H
H3C
Organic Chemistry OnLine ©2000
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
+
CN
CH3
CH3
CH3
CH3
HH
CN
H
CH3
H
H3C
Organic Chemistry OnLine ©2000
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
HH
NC
CH3
CH3
H
Organic Chemistry OnLine ©2000
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
HH
NC
CH3
CH3
H
Organic Chemistry OnLine ©2000
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
HH
NC
CH3
CH3
H+
CN
CH3
CH3
Organic Chemistry OnLine ©2000
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
CN
CN
H3C
Organic Chemistry OnLine ©2000
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
CN
CN
H3C+
CN
CN
H3C
Organic Chemistry OnLine ©2000
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
CH3
HH
CN
H
CH3
CH3
H
Organic Chemistry OnLine ©2000
Suggest a synthesis for the molecule shown on the right,using a cycloaddition reaction.
CH3
HH
CN
H
CH3
CH3
H+
CN
CH3
CH3
CH3
Organic Chemistry OnLine ©2000
CH3
Cl
Cycloadditions & Isomerism Draw all of the potential isomers from the cycloadditionreaction shown below.
Organic Chemistry OnLine ©2000
CH3
H
HClCH3
H
HCl
First, you must considerthat attack can occur
from either the top, or thebottom face.
Organic Chemistry OnLine ©2000
CH3
H
HClCH3
H
HCl
First, you must considerthat attack can occur
from either the top, or thebottom face.
Organic Chemistry OnLine ©2000
CH3
H
HClCH3
H
HCl
First, you must considerthat attack can occur
from either the top, or thebottom face.
H
CH3H
Cl
Organic Chemistry OnLine ©2000
CH3
H
HClCH3
H
HCl
First, you must considerthat attack can occur
from either the top, or thebottom face.
H
CH3H
Cl
H
H3CH
Cl
Organic Chemistry OnLine ©2000
CH3
H
HClCH3
H
HCl
First, you must considerthat attack can occur
from either the top, or thebottom face.
H
CH3H
Cl
H
H3CH
Cl
The compounds areenantiomers.
Organic Chemistry OnLine ©2000
CH3
H
HCl
CH3
H
Cl H
H
H
H
Cl
H
H H
CH3
Therefore, all additions will lead to the formation of a pairof enantiomers.
A pair of enantiomers;a racemic mixture.
Organic Chemistry OnLine ©2000
Next, the dienophile can approach the diene from either theendo (favored) or exo face.
CH3
H
ClHexo
CH3
H
Cl Hendo
Organic Chemistry OnLine ©2000
Next, the dienophile can approach the diene from either theendo (favored) or exo face.
CH3
H
ClHexo
CH3
H
Cl Hendo
CH3
H
HCl
Organic Chemistry OnLine ©2000
Next, the dienophile can approach the diene from either theendo (favored) or exo face.
CH3
H
ClHexo
CH3
H
Cl Hendo
CH3
H
HCl
H
H
H
Cl
H
H H
CH3
Organic Chemistry OnLine ©2000
Next, the dienophile can approach the diene from either theendo (favored) or exo face.
CH3
H
ClHexo
CH3
H
Cl Hendo
CH3
H
HCl
H
H
H
Cl
H
H H
CH3
CH3
H
ClH
Organic Chemistry OnLine ©2000
Next, the dienophile can approach the diene from either theendo (favored) or exo face.
CH3
H
ClHexo
CH3
H
Cl Hendo
CH3
H
HCl
H
H
H
Cl
H
H H
CH3
CH3
H
ClH
H
H
Cl
H
H
H H
CH3
Organic Chemistry OnLine ©2000
Next, the dienophile can approach the diene from either theendo (favored) or exo face.
CH3
H
ClHexo
CH3
H
Cl Hendo
CH3
H
HCl
H
H
H
Cl
H
H H
CH3
CH3
H
ClH
H
H
Cl
H
H
H H
CH3
(Each as a pair ofenantiomers.)
Organic Chemistry OnLine ©2000
CH3
Cl
CH3
Cl
syn
anti
H
H
H
Cl
H
H H
CH3
H
H
Cl
H
H
H H
CH3
endo exo
Further, the dienophile can approach syn or anti to the methylgroup on the diene.
Organic Chemistry OnLine ©2000
CH3
Cl
CH3
Cl
syn
anti
H
H
H
Cl
H
H H
CH3
H
H
Cl
H
H
H H
CH3
endo exo
Further, the dienophile can approach syn or anti to the methylgroup on the diene.
H
Cl
H
H
H
H H
CH3
Cl
H
H
H
H
H H
CH3
endo exo
Organic Chemistry OnLine ©2000
CH3
Cl
CH3
Cl
syn
anti
H
H
H
Cl
H
H H
CH3
H
H
Cl
H
H
H H
CH3
endo exo
Further, the dienophile can approach syn or anti to the methylgroup on the diene.
H
Cl
H
H
H
H H
CH3
Cl
H
H
H
H
H H
CH3
endo exo
i
e
Organic Chemistry OnLine ©2000
CH3
Cl
CH3
Cl
syn
anti
H
H
H
Cl
H
H H
CH3
H
H
Cl
H
H
H H
CH3
endo exo
Further, the dienophile can approach syn or anti to the methylgroup on the diene.
H
Cl
H
H
H
H H
CH3
Cl
H
H
H
H
H H
CH3
endo exo
i
e
These two are diasteromers.
Organic Chemistry OnLine ©2000
CH3
Cl
CH3
Cl
syn
anti
H
H
H
Cl
H
H H
CH3
H
H
Cl
H
H
H H
CH3
endo exo
Further, the dienophile can approach syn or anti to the methylgroup on the diene.
H
Cl
H
H
H
H H
CH3
Cl
H
H
H
H
H H
CH3
endo exo
i
e
These two are diasteromers.
i
e
Organic Chemistry OnLine ©2000
CH3
Cl
CH3
Cl
syn
anti
H
H
H
Cl
H
H H
CH3
H
H
Cl
H
H
H H
CH3
endo exo
Further, the dienophile can approach syn or anti to the methylgroup on the diene.
H
Cl
H
H
H
H H
CH3
Cl
H
H
H
H
H H
CH3
endo exo
i
e
These two are diasteromers.
i
e
These two are also diasteromers.
Organic Chemistry OnLine ©2000
CH3
Cl
H
H
H
Cl
H
H H
CH3
H
H
Cl
H
H
H H
CH3
H
Cl
H
H
H
H H
CH3
Cl
H
H
H
H
H H
CH3
CH3
Cl
The two sets are isomers, but are different chemical compounds.
syn
anti
i
e
i
e
cis- and trans-3-chloro-2-methylcyclohexene
endo exo
endo exo
cis- and trans-4-chloro-2-methylcyclohexene