Chapter 16
Conjugate Addition
Conjugate Pi bonds
Hydrocarbon containing
Different Kinds of Dienes
two double bonds: diene
three double bonds: triene
four double bonds: tetraene
many double bonds: polyene
Carbonyls compounds with conjugated Pi bond:
A Molecular Orbital Description of Stability
Stability of dienes
Why is conjugated diene more stable than isolated diene
diene?
?
H2C
H2C CH
CH
CH
CH
CH2
CH2
H2C
CH
CH
CH2
resonance contributors
CH2
CH
CH
CH2
resonance hybrid
The Molecular Orbitals of 1,3
1,3--Butadiene
Bonding MO: constructive (in-phase) overlap
Antibonding MO: destructive (out-of-phase) overlap
HOMO--LUMO
HOMO
The highest-energy molecular orbital of 1,3-butadiene
that contains electrons is ψ2 (HOMO)
The lowest-energy molecular orbital of 1,3-butadiene
that does not contain electrons is ψ3 (LUMO)
HOMO = the highest occupied molecular orbital
LUMO = the lowest unoccupied orbital
HOMO--LUMO
HOMO
π*2
π*1
E
π2
E
π*2
π*4
π1
π3
1,2--Addition & 1,4
1,2
1,4--Addition
to conjugated dienes
π1
For a conjugated diene
For an isolated diene
Electrophilic Addition Reactions of Isolated Dienes
Electrophilic Addition Reactions of conjugated Dienes
When only one mole of HBr is added, two products will be
formed
Addition occurs as if we have 2 separate double bonds
If only one mole of HBr is added, one of the double bonds
The product resulting from the reaction on the adjacent
will undergo addition
sp2 carbons is called the 1
1,2
1,22-addition product
The product resulting from the reaction on the conjugated
carbons is called the 1,41,4-addition product
Mechanism of Electrophilic Addition
Kinetic versus Thermodynamic control
Kinetic control
Thermodynamic control
Most stable
Kinetic versus Thermodynamic control
Kinetic versus Thermodynamic control
The thermodynamic product is the most stable product
The thermodynamic product predominates when the
reaction is reversible (thermodynamic control)
The kinetic product is the product that is formed most
rapidly
The kinetic product predominates when the reaction is
irreversible (kinetic control)
The 1,41,4-addition product has the greater number of alkyl
groups bonded to the sp2 carbon Æ MORE STABLE
1,4--Addition Polymers
1,4
The Diels
Diels--Alder Reaction
unstretched polymer
stretched rubber
Conformations of Dienes
H
H
H
H
H
H
Conformations of Dienes
H
s-trans
H
H
H
H
HH
s-cis
s prefix designates conformation around single bond
regardless of the stereochemistry at each double bond
s prefix is lower case (different from CahnCahn-IngoldIngold-Prelog
case)
S which designates configuration and is upper case)
H
H
H
H
H
H
s-trans
H
H
H
HH
s-cis
s prefix designates conformation around single bond
s prefix is lower case (different from CahnCahn-IngoldIngoldPrelog S which designates configuration and is upper
case)
Conformations of Dienes
s-trans
The Diels
Diels–
–Alder Reaction
Reaction:: a 1,41,4-Addition Reaction
s-cis
Both conformations allow electron delocalization via
overlap of p orbitals to give extended π system
The Diels
Diels–
–Alder Reaction: some examples
The conformation of the diene must be ss--cis to have
Diels--Alder reaction
Diels
The conformation of the diene must be ss--cis to have
Diels--Alder reaction
Diels
The Diels
Diels–
–Alder Reaction: some examples
Two Possible Configurations of Bridged Bicyclic Compounds
Effects of Conjugation in
α,β--Unsaturated Aldehydes and
α,β
Ketones
R and CH2
are trans
R and CH2
are Cis
Resonance Description
Acrolein
O
H2C
•• –
O ••
••
CHCH
O ••
C
C
C
C
C
C + ••
•• –
O ••
C
+C
C
••
Properties
Properties
α,β-Unsaturated aldehydes and ketones are
α,βmore polar than simple aldehydes and ketones.
α,β-Unsaturated aldehydes and ketones are
α,βmore polar than simple aldehydes and ketones.
α,β-Unsaturated aldehydes and ketones contain
α,βtwo possible sites for nucleophiles to attack
α,β-Unsaturated aldehydes and ketones contain
α,βtwo possible sites for nucleophiles to attack
carbonyl carbon
carbonyl carbon
β-carbon
β-carbon
••
O ••
C
βC
C
Dipole Moments
O
δ–
δ+
δ+
O δ–
δ+
Conjugate Addition to
µ = 2.7 D
µ = 3.7 D
α,β--Unsaturated Carbonyl Compounds
α,β
Butanal
trans--2-Butenal
trans
greater
separation of
positive and
negative charge
Nucleophilic Addition to
α,β-Unsaturated Aldehydes and Ketones
1,2--addition (direct addition)
1,2
Kinetic versus Thermodynamic Control
attack is faster at C=O
nucleophile attacks carbon of C=O
attack at β-carbon gives the more stable product
1,4--addition (conjugate addition)
1,4
nucleophile attacks β-carbon
O
O
C
C
C
C
+ H
Y
C
C
1,2--addition
1,2
H
O
C
C
C
Y
+ H
Y
1,4--addition
1,4
formed faster
major product under
conditions of kinetic
control (i.e. when
addition is not readily
reversible)
enoll
goes to keto form
under reaction
conditions
H
O
C
Y
C
C
O
O
C
C
C
C
+ H
C
Y
1,4--addition
1,4
k t fform is
keto
i iisolated
l t d
product of 1,41,4-addition
is more stable than
1,2--addition product
1,2
H
1,2--addition
1,2
1,4--addition
1,4
O
C
C
+ H
C=O is stronger
O
Y
C
C
1,2--Addition
1,2
C
O
than C=C
C
H
Y
C
Y
Y
C
C
C
Example
O
observed with strongly basic nucleophiles
CH3CH
CHCH + HC
Grignard reagents
g
CMgBr
1. THF
2. H3O+
LiAlH4
NaBH4
OH
Sodium acetylide
strongly basic nucleophiles add irreversibly
CH3CH
CHCHC
(84%)
CH
H
Example
1,4--Addition
1,4
O
observed with weakly basic nucleophiles
C6H5CH
CHCC6H5
cyanide ion (CN–)
thiolate ions
ethanol,
KCN
(RS–)
acetic acid
ammonia and amines
azide ion (N3
O
–)
C6H5CHCH2CC6H5
weakly basic nucleophiles add reversibly
CN
(93--96%)
(93
Example
Example
O
C6H5CH
KCN
CHCC6H5
ethanol,
••
via
O ••
C6H5CH
–
CH
••
CC6H5
CN
CH3
acetic acid
CN
(93--96%)
(93
HO–, H2O
C6H5CH2SH
•• –
•• O ••
O
C6H5CHCH2CC6H5
O
C6H5CH
CH
O
CC6H5
CH3
CN
(58%)
SCH2C6H5
Example
••
O ••
via
O
••
–
CH3
SCH2C6H5
CH3
α,β--Unsaturated Carbonyl Compounds
α,β
•• –
•• O ••
O
CH3
(58%)
Conjugate Addition of Organocopper Reagents to
HO–, H2O
C6H5CH2SH
SCH2C6H5
CH3
SCH2C6H5
Addition of Organocopper Reagents to
α,β-Unsaturated Aldehydes and Ketones
Example
O
+ LiCu(
LiCu(CH
CH3)2
CH3
The main use of organocopper reagents is to
form carbon
carbon--carbon bonds by conjugate
addition to α,β-unsaturated ketones.
1. diethyl ether
2. H2O
O
CH3
CH3
(98%)