Cyclo PDF

Pericyclic Reactions
Ø  Pericyclic reaction involves a cyclic redistribution of bonding

electrons through a concerted process (i.e, without intermediates)
Cycloaddi9on
Electrocyclic Sigmatropic
Pericyclic reactions
Group
Cheletropic
Transfer
1
CH-‐423 Course on Organic Synthesis; Course Instructor: Krishna P. Kaliappan
Cycloaddition Reactions
Ø  Cycloaddition reactions results in the formation of a new ring
Ø  Designated as [A+B]

A and B refers to number of atoms containing π-electrons
Ø  Three important classifications of cycloaddition reactions
(i) Diels-Alder reaction

(ii) [1,3]-Dipolar cycloaddition
(iii) [2+2] Cycloaddition
2
Diels-Alder Reaction
Discovered by Professor Otto Diels and his student Kurt
Alder in 1928 and received Nobel prize in 1950
Otto Diels (1876-1952) Kurt Alder (1902-1958)
“We explicitly reserve for ourselves the application of the

reaction developed by us to the solution of such problems”
3
Diels-Alder Reaction
Ø  Reaction between a conjugated diene and dienophile
Ø  Highly effective method for the formation of cyclohexene ring
diene dienophile
4
Classification of Diels-Alder Reaction
Ø  Normal [4+2]

Diene is electron-rich
Dienophile is electron-poor
Ø  Inverse electron-demand [4+2]

Diene is electron-poor
Dienophile is electron-rich
Ø  Hetero [4+2]

Hetero atom can be a part of Diene or
Dienophile or both
5
Requirements of Diene
Ø  Diene can be open chain or cyclic

Ø  Diene should be electron rich and reactivity should be
enhanced by electron donating group substituents
Open chain diene can acquire two conformations
s-cis s-trans
(reactive conformation) (unreactive conformation)
Two double bonds Two double bonds
are cis to each other are trans to each other
6
Requirements of Diene
Ø  The diene must adopt an s-cis conformation to be reactive
Ø  Cyclic dienes which adopt s-cis conformation are very reactive
Ø  Cyclic dienes which are permanently in s-trans conformation

are unreactive in Diels-Alder reaction
7
Preparation of Some Dienes
R
O OTf R
Tf2O, Py Pd(OAc)2, AcOK
Heck coupling
Grubb's 2nd
generation
catalyst
R Enyne metathesis
O
(1) TsNHNH2
(2) MeLi
Shapiro reaction
O Base, TMS-Cl OTMS
O OH
MgBr Dehydration
H3O+
8
Requirements of Dienophile
Ø  Dienophile can be open chain or cyclic
Ø  Dienophile should be electron deficient and reactivity enhanced

by electron withdrawing substituents
9
Preparation of Some Dienophiles
H2SO4
O NO2
Δ
O2N CH3
H H
OH O
KBrO3
1N H2SO4
OH O
O O
PhCH3NH
CF3COOH, THF
HCHO
Mannich reaction
(1) Hydrolysis
CO2R (2) Esterification CN NaOH, H2O2 CONH2
10
Stereochemistry of Diels-Alder Reaction
Ø  Diels-Alder reaction is stereospecific
Ø  Relative stereochemical relationship of diene and dienophile

is reproduced in the product
Ø  Diels-Alder reaction occurs due to the overlapping of p-

orbitals of diene and dienophile lying perpendicular to the
plane of carbon atoms
Ø  Hence, a given diene possess two faces namely top face and
bottom face
Ø  Dienophile can approach either of the faces and lead to

racemic mixture
11
Frontier Molecular Orbital (FMO) Approach
Ø  Highest Occupied Molecular Orbitals (HOMO) &

Lowest Unoccupied Molecular Orbitals (LUMO) are
known as Frontier Molecular Orbitals (FMO)
Theory:
1. The occupied orbitals of different molecules repel each
other.
2. The occupied orbitals of one molecule and the unoccupied
orbitals of the other (especially the HOMO and LUMO)
interact with each other causing attraction.
Ø  FMO simplifies the reactivity by interaction between HOMO

of one component & LUMO of other component
12
Frontier Molecular Orbital (FMO) Approach
MO of Diene: MO of Dienophile:
Ψ4*
π∗
Ψ3*
E E
Ψ2
π
Ψ1
Thermal Photochemical
Condition Condition
Thermal Photochemical
Condition Condition
13
Stereochemistry of Diels-Alder Reaction
Stereochemistry of both diene and dienophile retained in the
product
Reaction controls the relative stereochemistry at four
contiguous centers
top face
H H
H H H
H H H
H H H
H H H
H H
H H
H H
bottom face
14
Stereochemistry of Diene
Rule of Thumb:
Given the bottom face approach of dienophile:
-  Inside substituents of diene will become β-configuration in
the product
-  Outside substituents of diene will become α-configuration
in the product
Outside Inside
substituents substituents
15
Stereochemistry of Diene
Me
Me
CO2Me H
H
+ H CO2Me
H Me
Me MeO2C
MeO2C
H Me H
H
CO2Me Me
CO2Me
Me
CO2Me
H Me CO2Me
16
Stereochemistry of Dienophile
Given the bottom face approach of dienophile, substituents on
dienophile can take two different orientations with respect to
the plane of the diene called endo or exo
Ph Ph
H H
H H
“endo” Ph Ph “exo”
OHC CHO
Ph Ph
H H
H H
Ph Ph
OHC
CHO
17
Ph
Ph
endo H
H approach H
H
Ph
Ph
OHC OHC
Ph H
H
Ph
Ph
H
CHO
OHC
Ph
18
Ph Ph
H exo H
approach
H H
Ph Ph
CHO
CHO
Ph H
H
Ph
Ph
CHO CHO
Ph H
19
Alder’s endo Rule
endo mode of addition is usually preferred to exo addition due to
secondary orbital overlap between the dienophile’s activating
substituent and the diene.
H
H H
H
H
H
no secondary
secondary H H
orbital interaction
orbital interaction H
secondary orbital overlap no secondary orbital overlap

(endo) (exo)
20
Regiochemistry of Diels-Alder Reaction
For a mono-substituted diene, outcome of the product depends

on the carbon atom where it is substituted
Consider two classical cases, where the electron donating

substituent could be present at carbon 1 or carbon 2
1-substituted diene 2-substituted diene
21
1-substituted diene react to give mainly [1,2]-product
[1,2]-product
[1,3]-product
22
Regioselectivity for the preference of [1,2]-product can be
explained by considering the polarization of diene and dienophile
Connect the electron rich center of diene to electron deficient

center of dienophile
Electron Electron
rich deficient
center center
23
2-substituted diene react to give mainly [1,4]-substituted product
[1,4]-product
[1,3]-product
electron electron
rich deficient
center center
24
Elements of Symmetry in MO’s
Elements of Symmetry in MO’s of Dienes:
Ψ1 Ψ3* Ψ4*
Ψ2
Elements of Symmetry in MO’s of Dienophiles:
π π∗
25
Correlation Diagram
A σ4*
S σ3*
Ψ4* A
π∗ A A π∗
E
Ψ3* S
Ψ2 A
π S S π
Ψ1 S
A σ2
S σ1
26
Problem solving approach for D-A Reaction
First locate the diene and dienophile
Consider bottom face approach of dienophile
Look for stereochemistry of diene substituents in the product

(Inside substituents – β and outside substituents –α )
Look for stereochemistry of dienophile substituent (exo vs endo)
Regioselectivity if both diene and dienophile are unsymmetrical
27
H Me
H H
Me CO2Me CO2Me
+
H
Me Me H
OMe OMe
CO2Me CO2Me
+
OMe
CO2Me
28
OMe OMe
CO2Me
CO2Me
+
TMSO TMSO
Danishefsky’s diene
OMe
TMSO CO2Me
29
Problem Solving Approach for D-A Reaction
30
Problem Solving Approach for D-A Reaction
31
Synthetic Equivalence in D-A Reaction
Synthetic utility of DAR can be enhanced by the use of masked

functionality
As ketenes can not be used as such in DAR, ketene equivalents

with masked functionality provide an alternative choice
Commonly employed ketene equivalents are, α-Chloro

acrylonitrile and Nitro ethylene
α-Chloro acrylonitrile Nitro ethylene
32
O2N
O O
+ C
CH2 Cl CN
NO2
+
Nef reaction
NO2
KOH, DMSO
Cl CN Cl
+
CN
33
Commonly employed ethylene equivalent, Vinyl sulfone
34
Commonly employed acetylene equivalent, Vinyl sulfoxide
SOPh
SOPh SOPh
35
Commonly employed allene equivalent, Vinyl phosphonium salt
36
Chiral Auxiliary
A chiral auxiliary is a homochiral group that is temporarily

directly attached to an achiral substrate (R-X).
The modified substrate undergoes a diastereoselective

reaction
Finally, the chiral auxiliary is cleaved and recovered to give
a product (R-Y*) bearing a new stereogenic centre (or in
some cases several stereogenic centres).
e.g.
37
Chiral Auxiliary
Requirements for a Chiral Auxiliary:

The diastereoselective step to give R-Y*-Aux* must proceed
with very good stereo control
Cleavage of R-Y*-Aux* must occur under mild conditions and

with no racemization
The auxiliary Aux* ideally should be low cost
Both enantiomers of the auxiliary should be available

38
Commonly Used Chiral Auxiliaries
Corey’s
Evan’s 8-phenylmenthol Oppolzer’s sultam
oxazolidinone
39
Chiral Auxiliary: Corey’s 8-phenylmenthol
Asymmetric Diels-Alder Reaction
+ +
O
Me
Me
O
Me
OBn
or
BnO
+
BnO O
40
Chiral Auxiliary: Evan’s Oxazolidinone
Asymmetric Diels Alder Reaction
Me2Al Me2Al
Me2AlCl2 O O O
O
N O N O
BnOLi
HN O
O OBn
41
Intramolecular Diels-Alder Reaction (IMDA)
Type I IMDA :
Dienophile is attached to C-1 atom of diene

Results in the formation of fused bicyclic system
Fused bicyclic system
42
Intramolecular Diels-Alder Reaction (IMDA)
Type II IMDA:
Dienophile is attached to C-2 atom of diene
Type II IMDA generally results in the formation of bridged

bicyclic system, provided the ring formed other than six
member should be minimum seven member ring
Bridged bicyclic system
43
IMDA – Type I Examples
44
IMDA – Type I Examples
45
IMDA – Type II Examples
O O O
O
MeO2C MeO2C
46
Hetero Diels-Alder Reaction
Hetero Diene:
Hetero
atom is part of the diene
O O
MeO2C
OAc
EtO Me O OEt
PhS
OAc
47
Hetero Diels-Alder Reaction
Hetero Dienophile:
Hetero atom is part of the dienophile
O
Ts
N
CO2Me
48
Inverse electron demand D-A Reaction
Inverse electron-demand [4+2]:

Diene is electron-deficient
Dienophile is electron-rich
49
Inverse electron demand D-A Reaction
50
Ortho-Quinodimethanes
OTMS O
O
MgBr LiNH2, NH3, THF
CuI, TMS-Cl I
O O
Me3Si SiMe3 170 oC

Me3Si Me3Si
CpCo(CO)2
Me3Si Me3Si
O
O
1) CF3CO2H
CCl4, -30 oC H
H
Me3Si
2) Pb(O2CCF3)4 H H
H H
HO
Me3Si
Estrone
51
Ortho-Quinodimethanes
O
O
HN
HN 155 oC
Me O Me
O N N
155 oC
O
O
O Me
Me N
O N
155 oC
OMe N
N OMe
Me O Me
N
O N
180 oC
N NH
52
Photoenolization
R R R
O hν O OH
H H
R R R
R OH R
CO2Me CO2Me
MeO2C CO2Me H2O
CO2Me CO2Me
R R
R R R OH O
O O O
O hν OH
O
H
R O
R R
53
1,3-Dipolar Cycloaddition
X C X
C
B + B
A A
1,3-dipoles dipolarophile
C X C X
B + B
A A
1,3-dipoles dipolarophile
4-π electrons from 1,3-dipole and two electrons from dipolarophile
HOMO (Ψ2) of dipole
LUMO (Ψ2*) of dipolarophile
Reactants approach each another in parallel planes to permit

interaction between the HOMO and LUMO orbitals
54
Examples of Some 1,3-Dipoles
N N CR2 N N CR2 Diazoalkane
N N NR N N NR Azide
RC N NR RC N NR Nitrile imine
RC N CR2 RC N CR2 Nitrile ylide
RC N O RC N O Nitrile oxide
R
R2C N CR2 R2C N CR2 Azomethine ylide
R
R
R2C N O R2C N O Nitrone
R
R2C O O R2C O O Carbonyl oxide
R O R R O R Carbonyl ylide
55
N R
N C N R
δ+ N δ R
-
N C R
+ R N C R
Transition state is not very polar
Not strongly affected by solvent polarity
In most cases, reaction is a concerted [4πs + 2πs]

cycloaddition
56
Regioselectivity and Stereoselectivity
N Ph N
Ph N Ph cis-stilbene trans-stilbene N Ph
H H PhC N NPh H Ph
diphenylnitrilimine
Ph Ph Ph H
Syn addition with respect to dipolorophile

O2N N N N
p-nitrophenyl azide H3C H
H H
H OC3H7
N H3C OC3H7
O2N N N N
O2N N N
H H
H3C OC3H7 H3C H
H OC3H7
H Ph N
H Me N
Ph N H N
PhHC N N + +
H Me H Me
Phenyldiazomethane MeO2C CO2Me MeO2C CO2Me
MeO2C CO2Me
57
Stereochemistry of 1,3 dipolar cycloadditions
electron
deficient end
N
O
R
electron
electron rich end
rich end
+ N
N R
O
O
R
58
Nitrones and Nitrile Oxides in
R'
R' NHOH
R CHO R N
C O
H
Cl2 R N Et3N
R N OH R C N O
OH
Cl
PhN C O
R NO2 R C N O
O OH
R N
R C N O O Ra Ni R R
+ H2O
R R R
R
R
trans alkene LAH
R NH2
OH
R R
59
CH3 1) H3C OH H
H3C
N
H3C H H3C CH3
2) O N
H3C
O CH3 H
How?
H3C OH
N
H
CH3
H3C H
H3C H3C
CH3
O O N
N CH3 H3C
H
CH3
O
O O
H2C N N +
O N
N
60
CH3
H N
PhHC NCH3 + H2C C C N O
H Ph
O
NC
O
O O
R
R PhNCO R C5H11C CH
Et3N
CH2NO2 C N O
N C5H11
O
O O H O
N O
N toluene N HN
H2, Pd/C
OCMe3
CH3 OC(CH3)3 CH3 OC(CH3)3 Me
NaOCl MeO2C
H3CO2C H3CO2C
Me
H3C H3C O
OH
N
N N O
61
[2+2] Cycloadditions
[2s+2s] addition Not allowed
[2s+2s] addition hν
Allowed
Problem of incompatible symmetry is avoided by converting one

of them into excited state photochemically
Ground state of alkene Excited state of alkene
π∗ UV light π∗
(hν)
π π
62
Photochemical [2+2] Cycloadditions
Now combining excited state of alkene with ground state of

another one solves the symmetry problem
Excited state of alkene Ground state of alkene
π∗ π∗
π π
Alkene can dimerize photochemically in this way

63
Ø  Conjugated alkene absorbs UV light
O O * O
hν
O
O O
hν
Ø  Reaction is stereospecific

CO2Me O
O MeO2C H
CO2Me
hν
CO2Me
+
O
CO2Me MeO2C
Ø  Least hindered transition state is observed

64
Regioselectivity
O O
H
hν
H
O
O
H
hν
HOMO LUMO H
Alkene
HOMO
Ψ2
E O
Ψ1 Enone
LUMO
65
Enones with Olefins
O O
H
hν
+
H H
H
Caryophyllene
O O
O O O
CH2
+
CH2 + +
90%
O
CH3 CH3
H2C CH2
O hν, CH2Cl2 O
N O N HO
CH3 CH3
H H
O Ph CH3 O Grandisol
66
Enones with Olefins
O
hν O
H CO2Me
O O O p-TSA, MeOH
hν O
reflux O
O
O
H
O
O MeO2C H
CO2Me
+
MeO2C H
CO2Me
67
Enones with Olefins
favored
O O O
O H H
hν O
O
O
H3C H3C
O CH3 CH3 O
CH3 H3C H
disfavored
O
R
O R O
hν R
O O MeO2C
H
O O
68
Enones with Allenes
O O O
H H
H2C C CH2
+
hν
H H
2 : 1
Enones with Acetylenes

O
O O
hν O O
O O
CO2Me MeO2C
+
MeO2C
CO2Me
69
DeMayo Reaction (Enol with Alkene)
O O
OH OH
hν
N N
O O
O O
H O H
Base
H H
N N
O O
lycorine
70
Other Examples
H
hν H
H
Me2CO
H
Ph Ph Ph CO2H
CO2H
+
Ph HO2C Ph
HO2C CO2H
71
Thermal [2+2] Cycloadditions
HOMO/LUMO combination is antibonding at one end
alkene
LUMO
Rotate 90o
alkene
HOMO
If HOMO & LUMO approaches perpendicular to each other
2πs+2πa
interaction
72
It must have two double bonds at same carbon atom
R
R
C O
N C O
R
isocyanate
ketene
O O
C heat
O O
C heat
N
N R SO2Cl
R SO2Cl
O O O
O H H
hν H2C CH2 isomerisation
2πs + 2πa
thermal cyclization H H
73
Ketenes
Central atom is sp carbon atom with extra π bond
Electrophilic, low-energy LUMO
Preparation of Ketenes:
O H
C O
O H
O
Et3N
C O
Cl
H
O
Zn C O
Cl
Cl
O R
hν
N2 C O
R
H
74
Thermal [2+2] Cycloadditions of Ketenes
O H O :Zn H O ZnCl
C Zn/AcOH
Cl Cl Cl
H Cl H Cl
H O H O H
O
AcOH mCPBA
O
Cl H
H H H H H
O O
+ C O C +
CH2
Sterochemistry
can be control
75
O
Ph CH3 Cl Cl O
Ph
Cl3C Cl O CH2N2 Cl
Zn-Cu, Et2O Cl
O O CH3
CH3
CH3 CH3 RO Ar
O H O
Cl3C Cl
Cl
Zn-Cu, Et2O
H Cl
1) H
O
C N
C N
2) H2O
H
OMe
OMe
76
Reaction of ketene with enamines
NR2 O
H
+ C O NR2
H
Difluorodihaloethylene
With Olefins: F X
F2C CX2 F X
R
X = F, Cl
R
With Acetylene-Biradical Mechanism:
F X
O O
F2C CX2 Hydrolysis
R F X
X = F, Cl
R R
77
β-lactams by [2+2] cycloadditions
R
R R H2C
CH2 R
+
C +
NR NR NR O C NR
O O
O
Imine Isocynate
Cl Cl Cl
O Cl
Cl Et3N
Cl C NPh NPh
Cl O O
Staudinger reaction
Cl
Cl
Cl NaHCO3 Cl
H
N H2O N NH
O C N O SO2Cl O
O S O
SO2Cl
O O
78
Synthesis of Cubane
Cubane
Challenges
1. Six - 4 membered rings fused together
2. No functional groups
3. Highly strained
4. Low molecular weight C8H8=104
79
Retrosynthesis
1. 4-membered rings could be formed by photochemical reaction
2. How many 4-membered rings could be formed by photochemical

reaction?
How about this?
Many Problems:
1. Reversibility
2. Stability of the starting material
3. Intermolecular reaction
80
Cubane
Solutions
1. Introduce a functional group

2. Which functional group?
a. The functional group should be removed easily
b. It also should be formed easily from another precursor
c. This should be introduced along with either ring contraction

or ring expansion
Ring Expansion or Ring Contraction?
Ring Expansion
Ring Contraction
Which functional group could be formed along with this reaction? 81

Cubane
Ring Expansion or Ring Contraction?
O O Difficult
sp2 carbon in cubane?
O
CO2H
Possible
Br Favorskii
Therefore, need to go for ring contraction

- Favorskii reaction will be better
82
Cubane
One Carboxylic Acid or Two Carboxylic Acids?
CO2H CO2H
or
HO2C
1.  One carboxylic acid- precursor will have only one 5-membered ring
and remaining will be 4-membered
2. Two carboxylic acid- precursor will have only two 5-membered ring
and remaining will be 4-membered
83
Cubane
Two Carboxylic Acids
Where and what is the relationship?
Molecule could be symmetrical or non-symmetrical
CO2H CO2H CO2H
CO2H
CO2H HO2C
1,2 1,3 1,4
Which will be easier from synthetic point of view?
84
Cubane
Quasi-Favorskii Rearrangement
O CO2H
Br
Br
CO2H
O
1,2
O
Br CO2H
Br CO2H
O 1,3
O CO2H O
Br Br
O
Br HO2C
1,4 Br
O
85
Cubane
Two disconnections for photochemical reaction
O O O
Br Br Br
O O O
Br Br Br
O
O
O
Br same O
Br
Br
Br
Br O
+ Br
O
86
Cubane
Problems in Starting Material
1. Cyclopentadienone is highly unstable
2. Difficult to prepare
Synthesis
O O
O
NBS Br2 Br Et3N
hν
Br Br Br
O
O Br 1) PPTS O O
Br
[4+2]
Br HO OH
O
2) aq. HCl O
(Mono removal)
Br
Br
87
Cubane synthesis
O O O O O
Br O
Br Br
hν 10% KOH
O
O
Br HO2C
Br
O O
Br O O
1) SOCl2 Cumene Br 75% H2SO4
2) Pyridine
tBuOOH
tBuO
3C
O CO2H CO3tBu
Br 1) SOCl2
25% KOH
2) Pyridine
tBuOOH
diisopropylbenzene Philip Eaton, University of Chicago
88
Cubane synthesis
Modified Synthesis
O
O O Br2 O O
HO OH Br
Br
H+ Br
O O O
Br Br
1) NaOH 1) hν
O
2) H+ 2) H2SO4
O
Br
Br
CO2H
1) NaOH -CO2
2) H+
HO2C
89

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Pericyclic Reactions

Ø Pericyclic reaction involves a cyclic redistribution of bonding

Ø Cycloaddition reactions results in the formation of a new ring

Ø Designated as [A+B]

Ø Three important classifications of cycloaddition reactions

(i) Diels-Alder reaction

Otto Diels (1876-1952) Kurt Alder (1902-1958)

“We explicitly reserve for ourselves the application of the

Ø Reaction between a conjugated diene and dienophile

Ø Highly effective method for the formation of cyclohexene ring

Ø Normal [4+2]

Ø Inverse electron-demand [4+2]

Ø Hetero [4+2]

Ø Diene can be open chain or cyclic

Open chain diene can acquire two conformations

Ø The diene must adopt an s-cis conformation to be reactive

Ø Cyclic dienes which are permanently in s-trans conformation

O Base, TMS-Cl OTMS

Ø Dienophile should be electron deficient and reactivity enhanced

Ø Diels-Alder reaction is stereospecific

Ø Relative stereochemical relationship of diene and dienophile

Ø Diels-Alder reaction occurs due to the overlapping of p-

Ø Dienophile can approach either of the faces and lead to

Ø Highest Occupied Molecular Orbitals (HOMO) &

Ø FMO simplifies the reactivity by interaction between HOMO

secondary orbital overlap no secondary orbital overlap

For a mono-substituted diene, outcome of the product depends

Consider two classical cases, where the electron donating

1-substituted diene 2-substituted diene

1-substituted diene react to give mainly [1,2]-product

Connect the electron rich center of diene to electron deficient

2-substituted diene react to give mainly [1,4]-substituted product

Elements of Symmetry in MO’s of Dienes:

Elements of Symmetry in MO’s of Dienophiles:

First locate the diene and dienophile

Consider bottom face approach of dienophile

Look for stereochemistry of diene substituents in the product

Look for stereochemistry of dienophile substituent (exo vs endo)

Regioselectivity if both diene and dienophile are unsymmetrical

Synthetic utility of DAR can be enhanced by the use of masked

As ketenes can not be used as such in DAR, ketene equivalents

Commonly employed ketene equivalents are, α-Chloro

α-Chloro acrylonitrile Nitro ethylene

Commonly employed allene equivalent, Vinyl phosphonium salt

A chiral auxiliary is a homochiral group that is temporarily

The modified substrate undergoes a diastereoselective

Requirements for a Chiral Auxiliary:

Cleavage of R-Y*-Aux* must occur under mild conditions and

The auxiliary Aux* ideally should be low cost

Both enantiomers of the auxiliary should be available

Dienophile is attached to C-1 atom of diene

Fused bicyclic system

Type II IMDA generally results in the formation of bridged

Bridged bicyclic system

Inverse electron-demand [4+2]:

Me3Si SiMe3 170 oC

4-π electrons from 1,3-dipole and two electrons from dipolarophile

HOMO (Ψ2) of dipole

LUMO (Ψ2*) of dipolarophile

Reactants approach each another in parallel planes to permit

RC N CR2 RC N CR2 Nitrile ylide

R2C O O R2C O O Carbonyl oxide

Ø  Pericyclic reaction involves a cyclic redistribution of bonding

Ø  Cycloaddition reactions results in the formation of a new ring

Ø  Designated as [A+B]

Ø  Three important classifications of cycloaddition reactions

Ø  Reaction between a conjugated diene and dienophile

Ø  Highly effective method for the formation of cyclohexene ring

Ø  Normal [4+2]

Ø  Inverse electron-demand [4+2]

Ø  Hetero [4+2]

Ø  Diene can be open chain or cyclic

Ø  The diene must adopt an s-cis conformation to be reactive

Ø  Cyclic dienes which are permanently in s-trans conformation

Ø  Dienophile should be electron deficient and reactivity enhanced

Ø  Diels-Alder reaction is stereospecific

Ø  Relative stereochemical relationship of diene and dienophile

Ø  Diels-Alder reaction occurs due to the overlapping of p-

Ø  Dienophile can approach either of the faces and lead to

Ø  Highest Occupied Molecular Orbitals (HOMO) &

Ø  FMO simplifies the reactivity by interaction between HOMO

Cleavage of R-Y-Aux must occur under mild conditions and

Ø  Reaction is stereospecific

Ø  Least hindered transition state is observed