Organic Lecture Series
Conjugated
Systems
& Pericyclic
Reactions
1
Conjugated Dienes
Organic Lecture Series
from heats of hydrogenation-relative stabilities of
conjugated vs unconjugated dienes can be studied:
N ame
Structural
Formula
ΔH0
kJ (kcal)/mol
1-Butene
-127 (-30.3)
1-Penten e
-126 (-30.1)
cis-2-Butene
-120 (-28.6)
trans-2-Buten e
-115 (-27.6)
1,3-Butadien e
-237 (-56.5)
t rans-1,3-Pentad iene
-226 (-54.1)
1,4-Pentadien e
-254 (-60.8)
conjugated
2
Organic Lecture Series
Conjugated Dienes
conjugation of the double bonds in
1,3-butadiene gives an extra stability of
approximately 17 kJ (4.1 kcal)/mol
2
+ 2 H2
catalyst
0
ΔH = 2(-127 kJ/mol)
2
= -254 kJ/mol)
+ 2 H2
ΔH 0 = -237 kJ/mol
catalyst
3
Organic Lecture Series
Conjugated Dienes
The π systems of the 2 olefins overlap
H
C
H
C
H2C
CH2
C
C
C
C
S-cis conformer
4
Conjugated Dienes
Organic Lecture Series
CH2
H
C
C
H
H2 C
C
C
C
C
S-Trans conformer
5
Organic Lecture Series
Summary of C—C Bond Reactions
Nucleophilic displacement
of a leaving group by “R - ”
‰Gilman & Grignard additions
‰Alkyne and CN anions
‰Alkylation of enolates
‰Alkylation of enamines
6
Organic Lecture Series
Nucleophilic addition
To carbonyl & carboxyl groups
‰ Gilman, Grignard & organolithium
‰ Alkyne and CN anions
‰ Aldol reactions
‰ Claisen & Dieckmann
‰ Enamine acylations
‰ Wittig & variations
7
Organic Lecture Series
Conjugate addition to α,β- unsaturated carbonyls
‰ Michael reaction
Carbene / carbenoid additions
‰Simmons-Smith
‰cyclopropanations
Electrophilic Aromatic Substitutions
‰ Friedel Crafts alkylation & acylations
‰ Diazonium with CN
8
Organic Lecture Series
Conjugated Systems
– systems containing conjugated double bonds,
not just those of dienes, are more stable than
those containing unconjugated double bonds
O
O
2-Cyclohexenone
(more s table)
3-Cycloh exenone
(less s table)
Most significant are α,β-unsaturated carbonyl
9
1,2 vs 1,4-Addition
Organic Lecture Series
OH
Nu
O
2
1 ,2 A d d itio n
K in e tic P ro d u c t
RLi and R M gB r
1
3
4
O
1 ,4 A d d itio n
T h e rm o d y n a m ic P ro d u c t
R 2 C u L i a n d R M g B r/C u
Nu
10
Organic Lecture Series
Simple Rxn Coordinate Diagram
Δ H is (-)
e.g. an Sn2 Mechanism
11
Organic Lecture Series
A Two Step Mechanism:
≠
≠
Δ H is (-)
e.g. an Sn1 Mechanism
12
Organic Lecture Series
1,2 vs 1,4-Addition
• Addition of 1 mol of HBr to butadiene at
-78°C gives a mixture of two constitutional
isomers:
CH2 = CH- CH= CH2 + HBr
1,3-Butadiene
-78°C
Br H
Br
H
CH2 = CH- CH- CH 2 + CH2 - CH= CH- CH 2
1-Bromo-2-butene
3-Bromo-1-butene
10%
90%
(1,4-addition)
(1,2-addition)
– these products can be explained by the
following two-step mechanism
13
1,2- and 1,4-Addition
Organic Lecture Series
the key intermediate is a resonance-stabilized allylic
carbocation:
2
2
2
2
2
2
2
2
14
Organic Lecture Series
2
2
2
2
2
2
2
2
90%
10%
15
Organic Lecture Series
Kinetic vs Thermodynamic Control
90%
10%
Δ Go = Δ Ho – T ΔSo Gibbs Free energy
For transition states: Δ
G≠ = Δ H ≠– T ΔS≠
16
Organic Lecture Series
Diels-Alder Reaction
Dienophile
Diene
Cycloadduct
Dienophile is an alkene which is a
reactant in the Diels-Alder reaction.
17
Diels-Alder Reaction
Organic Lecture Series
• Diels-Alder reaction: a cycloaddition
reaction of a conjugated diene and
certain types of double and triple bonds
– dienophile: “diene-loving”
– Diels-Alder adduct: the product of a DielsAlder reaction
O
O
+
1,3-Butadiene
(a diene)
3-Buten-2-one
(a dienophile)
Diels-Alder adduct
18
Organic Lecture Series
– alkynes also function as dienophiles
COOEt
COOEt
+
COOEt
1,3-butadiene
Diethyl
(a diene)
2-butynedioate
(a dienophile)
COOEt
Diels-Alder adduct
– cycloaddition reaction: a reaction in which
two reactants add together in a single step to
form a cyclic product
19
Organic Lecture Series
– the Diels-Alder reaction is shown in the
following way:
Cyclohexene
products
Diene
Dienophile
Adduct
• the special value of D-A reactions are that they
(1) form six-membered rings
(2) form 2 new C-C bonds at the same time
(3) are stereospecific and regioselective
20
Organic Lecture Series
• Mechanism
– no evidence for the participation of either
radical or ionic intermediates
– the Diels-Alder reaction is a pericyclic
reaction
• Pericyclic reaction:
reaction a reaction that
takes place in a single step, without
intermediates, and involves a cyclic
redistribution of bonding electrons
21
Organic Lecture Series
– the conformation of the diene must be s-cis
s-t rans
conformation
(lower in en ergy)
s-cis
con formation
(higher in en ergy)
22
Organic Lecture Series
– (2Z,4Z)-2,4-hexadiene is unreactive in DielsAlder reactions because nonbonded
interactions prevent it from assuming the
planar s-cis conformation
methyl grou ps
forced clos er th an
allow ed by van
der Waals radii
s-t rans conformation
s-cis conformation
(low er energy)
(h igh er energy)
(2Z,4Z)-2,4-Hexadiene
23
Organic Lecture Series
reaction is facilitated by a combination of electronwithdrawing substituents on the dienophile and
electron-releasing substituents on the diene
200°C
pressure
+
1,3-Butadiene Ethylene
Cyclohexene
O
O
140°C
+
1,3-Butadiene 3-Buten-2-one
O
O
+
2,3-Dimethyl- 3-Buten-2-one
1,3-butadiene
30°C
24
Organic Lecture Series
Electron-Releasing
Groups
Electron-Withdrawing
Groups
- CH 3 , alkyl group s
- CH O (ald ehyde, ketone)
- OR (ether)
- COOH (carb oxyl)
- OOCR (es ter)
- COOR (es ter)
- NO 2 (nitro)
-C
Use these to activate the diene
ERG
N (cyano)
Use these to activate the dienophile
EWG
25
Organic Lecture Series
Stereochemistry of the Dienophile
the configuration of the dienophile is retained
COOCH3
COOCH3
+
COOCH3
A cis
dien op hile)
H3 COOC
COOCH3
D imethyl cis-4-cyclohexen e1,2-dicarb oxylate
COOCH3
+
COOCH3
A t rans
d ienophile)
cis-alkene gives cis products
COOCH3
D imeth yl t rans-4-cyclohexene1,2-dicarboxylate
26
Stereochemistry of the Diene Organic Lecture Series
the configuration of the diene is retained:
CH3
H3 C
O
+
CH3
CH3
+
CH3
H
O
O
O
H3 C
O
H3 C
H
O
H
O
O
O
O
O
H3 C
H
O
27
Stereochemistry of the Diene Organic Lecture Series
The diene’s substitutents are turned “inside out”
28
Organic Lecture Series
B
A
B
C
C
D
A
B ro ta te s c o u n te rc lo c k w is e
C ro ta te s c lo c k w is e
T h is is c a lle d :
D is ro ta tio n
D
π bond
B
C
A
D
2 σ bonds
29
Organic Lecture Series
Summary
30
Summary
Organic Lecture Series
31