Pericyclic Reactions 6 Lectures, Year 3, Michaelmas 2014: Jonathan - Burton@chem - Ox.ac - Uk

Pericyclic Reactions 1
Pericyclic Reactions
6 Lectures, Year 3, Michaelmas 2014
jonathan.burton@chem.ox.ac.uk
HOMO diene
O
O π4s 6 electrons
no nodes
Hückel
O
(4q + 2)s = 1 π2s allowed ✓
O (4r)a = 0
Total = 1
O odd ✓ LUMO dienophile
allowed construcZve overlap ✓
h)p://burton.chem.ox.ac.uk/teaching.html
︎ ︎Pericyclic Reac+ons, Oxford Chemistry Primer no. 67; Ian Fleming
︎ Organic Chemistry Jonathan Clayden, Nick Greeves, Stuart Warren, Peter Wothers
Advanced Organic Chemistry: Reac+ons, Mechanisms and Structures; Jerry March
Fron+er Orbitals and Organic Chemical Reac+ons; Ian Fleming
Molecular Orbitals & Organic Chemical Reac+ons; Ian Fleming
Modern Physical Organic Chemistry; Eric Anslyn and Dennis Docherty

Synopsis

The nature of pericyclic reacZons

Examples of pericyclic reacZons

Drawing molecular orbitals

CorrelaZon diagrams

The Woodward-‐Hoffmann rule

FronZer Molecular Orbitals

Möbius-‐Hückel Method

CycloaddiZons

Electrocyclic reacZons

Sigmatropic rearrangements

Group transfer reacZons

The nature of pericyclic reac>ons

Ionic reacZons – may or may not have an intermediate Me Me
Me
Me Nu Me
X Me Me
Me Me Me Nu
Me Me
Me
X Me
SN1 reacZons are stepwise and have a defined intermediate Me
Me Me Nu
Me
‡
Me Me Me ‡
($) ($) Me
Nu + H I Nu I Nu H + I (") (")
Et Et H Et Nu I
Et H
SN2 reacZons are concerted and have no intermediate
In ionic reacZons the curly arrows idenZfy where the

electrons have come from and where they are going and
which bonds have been made and which broken. Me
H I
Me
Et
Nu H
Radical reacZons involve the correlated movement of single Et
electrons
NC NC
N N
N frequently shortened to N
CN CN
Pericyclic Reac>ons

Third disZnct class of reacZons

Pericyclic reacZons – ReacZons in which all first-‐order changes in bonding relaZonships take
place in concert on a closed curve. R. B. Woodward and R. Hoffmann 1969.

i.e. the reacZons have cyclic transiZon states in which all bond-‐forming and bond-‐
breaking take place in a concerted manner without the formaZon of an intermediate.
Pericyclic reacZons involve a transiZon state with a cyclic array of interacZng orbitals; a
reorganisaZon of σ and π-‐bonds occurs within this cyclic array.
Originally termed ‘ no mechanism reacZons’ – they could not be explained by standard
nucleophile/electrophile mechanisms.
O O
H H
O O
O O
No absolute sense in which the electrons flow from one component to another;
however, someZmes it is more sensible to push the arrows in only one direcZon.
Here curly arrows are used to show which bonds are being made/broken rather than
the direcZon of flow of electrons.

Pericyclic ReacZons – four classes.

CycloaddiZons -‐ Two components come together to form two new σ-‐bonds at the ends of
both components and joining them together to form a ring.
O O
Me O Me O
O O N N
Me Me
O O
Cheletropic reacZons are a sub-‐class of cycloaddiZon reacZons in which the two σ – bonds
are made or broken to the same atom.

O

+ CO
Electrocyclic ReacZons – Unimolecular reacZons characterised by the forma>on of a ring from an open chain
conjugated system with a σ-‐bond forming across the ends of the conjugated system.

Sigmatropic rearrangements – Unimolecular isomerisa>ons which formally involve the

overall movement of a σ-‐bond from one posiZon to another.
O O
Cope rearrangement Claisen rearrangement

MeO OMe
OH OH
H H
H
[1,5]-‐hydride shiK
Group transfer – appear to be a mix of a sigmatropic rearrangement and a cycloaddiZon.
They are bimolecular and so are not sigmatropic rearrangements, and no ring is formed so
they are not cycloaddiZons.
O O
H H H H
O O O O
O O •
O
O
O O
Alder-‐ene -‐ reac>ons

N N N N
Ph O H H
Se H
Ph O H H
Se
H
diimide reduc>on

Require a theory/theories to explain these results

O O O O
heat
O O O X O
O O O O
Me Me Me
heat heat
Me
Me Me Me Me
heat H
Me Me H [1,7] H Me
H Me [1,5] H [1,5] Me
H X
H
H
heat H
H Me
H Me Me
[1,7]
Me [1,5]
H
Hückel Molecular Orbital Theory for Linear π-‐systems.

Applicable to conjugated planar cyclic and acyclic systems.

Only the π-‐system is included; the σ-‐framework is ignored (in reality σ-‐framework affects π-‐system).

Used to calculate the wave funcZons (ψk) and hence rela+ve energies by the LCAO method.
n
MO = ψk, AO = ϕi and ψ = Σ
ckiϕi i.e. ψk = c1ϕ1 + c2ϕ2 + c3ϕ3 + c4ϕ4 + c5ϕ5 …..
0.500 $0.707 0.500
i = 1
k = MO number (1→n); i = atom posiZon in π system (1→n); n = number of p-‐orbitals

For n contribuZng p-‐orbitals there will be n molecular orbitals 0.707 $0.707
cki = (2/(n + 1))1/2•sin(πki/(n + 1))
ϕ1 ϕ2 ϕ3 ϕ4
For each MO ψk Σ ci2 = 1 (normalisaZon) i.e. the sum of the squares of the
coefficients for any MO must be 1.
0.500 0.707 0.500
For each AO ϕi Σ ck2 = 1 i.e. the sum of the squares of the coefficients for any AO over all MOs must be 1.

Each MO must be symmetric or anZsymmetric with respect to any symmetry operaZon of the molecule.

Molecular Orbital Energies = Ek = α + mjβ mj = 2cos[jπ/(n+1)] j = 1, 2……n

To draw a molecular orbital diagram:

i)  count the number of p-‐orbitals – n
ii)  count the number of electrons – π-‐bond = 2, unpaired electron = 1, carbanion = 2, carbocaZon = 0
iii)  draw n horizontal lines stacked on top of one another to represent the MOs
iv)  draw the molecular orbitals as the combinaZon of p-‐orbitals with an increasing number of nodes from 0 for
ψ1 to n-‐1 for ψn such that each MO is symmetric or an0symmetric with respect to any symmetry
opera0on of the molecule.
v)  if the number of nodes is even then the terminal orbital coefficients will be the same phase increasing
vi)  if the number of nodes is odd then the terminal coefficients will be of opposite phase number of nodes
ψ6 5
ψ5
ψ4 ψ5 4
ψ3
ψ2 ψ4 •
ψ3 ψ4 3
non#bonding ψ2 • ψ3 • •
ψ3
ψ2 2
ψ1 ψ2 •
ψ1
ψ1 ψ2
ψ1 1
ψ1
0
ethene allyl butadiene pentadienyl hexatriene

1,3,5-‐Hexatriene
six 2p atomic orbitals give 6π molecular orbitals; n = 6, j = 1, 2, 3, 4, 5, 6

mj = 2cos(π/7) = 1.80 2cos(2π/7) = 1.25 2cos(3π/7) = 0.45......
and the corresponding negaZve values
energy E = α + 1.80β α + 1.25β α + 0.45β α – 0.45β…..etc
no.
MO energy HMOT MO (calculated)
nodes
ψ6 5 α -‐ 1.80β %0.418 %0.521 %0.232

0.232 0.521 0.418
ψ5 4 α -‐ 1.25β &0.521 0.232 0.418

0.418 0.232 &0.521
ψ4 3 α -‐ 0.45β &0.232 0.418 &0.521

0.521 &0.418 0.232
α
α +
ψ3 2 0.232 '0.418 0.521
0.45β
0.521 '0.418 0.232

α +
ψ2 1 0.521 (0.232 (0.418
1.25β
0.418 0.232 (0.521
α +
ψ1 0 0.418 0.521 0.232
1.80β
0.232 0.521 0.418
stabilisaZon energy = Estab= 2(3α + 3.5β) = 6α + 7β remember Estab (ethene) = 2α + 2β
The HOMO of (neutral) polyenes can be readily constructed by puxng nodes on the single bonds; hence the HOMO
appears to be alternaZng isolated π-‐bonding pairs.

The LUMO of (neutral) polyenes can be constructed by beginning with an ‘isolated’ p-‐orbital and then alternaZng
‘isolated’ π-‐bonding pairs and ending with an ‘isolated’ p-‐orbital.
The HOMO and LUMO are termed the FronZer Orbitals.
• • • • • • • • • • • •
HOMO LUMO
CorrelaZon Diagrams

During a pericyclic reacZon the orbitals of the starZng material are smoothly converted into the orbitals of the
product.

This means that the symmetry of the orbitals with respect to any symmetry operaZons of the molecule must be
conserved in moving from the starZng material(s) to product – this is the ‘ConservaZon of Orbital Symmetry’, which
is readily depicted in an ‘orbital correlaZon diagram’
Draw bare bones of reacZon.
IdenZfy orbitals undergoing change.
Draw sensible approach of substrates.

σ σ
IdenZfy symmetry elements maintained during reacZon.
σ4
Rank orbitals approximately by energy.
ψ4
σ3
Classify each orbital with respect to the symmetry
element(s) conserved during reacZon. π* π*
Construct orbital correlaZon diagram connecZng orbitals

of starZng materials with those closest in energy and of the ψ3
same symmetry in the product.
In the Diels-‐Alder reacZon a plane of symmetry, ψ2

perpendicular to the molecular planes of both the diene
and dienophile and passing through the double bond of the π π
dienophile and the central single bond of the diene.
ψ1
In the orbital correlaZon diagram of the Diels-‐ Alder σ2
reacZon all interacZng bonding orbitals in the diene/
dienophile are correlated with new bonding orbitals in the σ1
product. The reacZon is thermally allowed.
CorrelaZon diagram for [2+2] cycloaddiZon of alkenes
IdenZfy orbitals undergoing change (curly arrows tell us σ2 σ2

which orbitals these are) – π.
σ1 σ1
Draw sensible approach of substrates – in this case face
on approach of the two alkenes for maximum orbital σ1σ2 σ1σ2
overlap.
σ4
IdenZfy symmetry elements maintained during reacZon – π4
in this case two planes of symmetry, σ1 and σ2.
σ3
Rank orbitals approximately by energy.
π3
Classify each orbital with respect to symmetry element(s)
conserved during reacZon.
Construct orbital correlaZon diagram connecZng orbitals π2

of starZng materials with those closest in energy and of the
same symmetry in the product.
Here the ground state π12π22 does not correlate with the π1
σ2
ground sate of the product (σ12σ22) but with a doubly
excited state σ12σ32 – the thermal [2+2] cycloaddiZon of
alkenes is thermally disallowed. σ1
CorrelaZon diagram for electrocyclic reacZons

Me
Z,E : E,E 20,000:1
Me
Me Longuet-‐Higgins & Abrahamson, J. Am. Chem. Soc., 1965, 87, 2045.
Me
There are two modes of opening – conrotatory or disrotatory

Conrotatory – rota+on around the axes of the σ-‐bonds (do\ed lines ) occurs in the same direc+on -‐
throughout this process the molecule retains a C2-‐axis which passes through the plane of the molecule and the
breaking σ bond.
C2
plan view
Disrotatory – rota+on around the axes of the σ-‐bonds (do\ed lines) occurs in opposite direc+ons –
throughout this process the molecule retains a plane of symmetry which is perpendicular to the plane of
the molecule and passes through the breaking σ-‐bond
σ
plan view
CorrelaZon diagram for electrocyclic reacZons.

IdenZfy orbitals undergoing change (curly arrows) – σ and π. molecular)
The orbitals undergoing change are either symmetric or anZsymmetric with respect to the plane
symmetry elements preserved during the reacZon.
Rank orbitals approximately by energy. C2 σ
Label orbitals as ‘S’ or ‘A’.
Construct orbital correlaZon diagram connecZng orbitals of starZng materials
with those closest in energy and of the same symmetry in the product.
R R R
R conrotatory disrotatory
R R
under C2 under σ
ψ4 R R R ψ4
R R
σ* R
ψ3 R R R ψ3
R
R π* R
ψ2 R R R ψ2
R
R π R
ψ1 R R R ψ1
R
R σ R
R R R
R conrotatory disrotatory molecular)
R R plane
under C2 under σ
C2 σ
ψ4 R R R ψ4
R R
σ* R
ψ3 R R R ψ3
R
R π* R
ψ2 R R R ψ2
R
R π R
ψ1 R R R ψ1
R
R σ R
In the conrotatory mode, all ground state bonding orbitals in cyclobutene (σ2π2) correlate with ground state
bonding orbitals in butadiene (ψ12ψ22) – the conrotatory opening of butadiene is thermally allowed (favoured).
In the disrotatory mode, the ground state bonding orbitals in cyclobutene (σ2π2) correlate with a doubly excited
state of butadiene (ψ12ψ32) – the disrotatory opening of butadiene is thermally forbidden (disfavoured).
The photochemical ring closure of butadiene to give cyclobutene is disrotatory.
The 1st excited sate of butadiene is ψ12ψ21ψ31 which correlates smoothly with the 1st
hν
excited sate of cyclobutene (σ2π1π*1); under conrotatory ring closure ψ12ψ21ψ31
correlates with a much high energy state in cyclobutene (σ1π2σ*1).
CorrelaZon diagrams can be disZlled into a simple rule for predicZng which pericyclic reacZons are
“allowed”.

The Woodward-‐Hoffmann Rules:
A ground state pericyclic reacZon is symmetry allowed when the total number of (4q + 2)s and (4r)a
components is odd (q and r must be integers).
A pericyclic change in the first electronically excited state (i.e. a photochemical reacZon) is symmetry-‐
allowed when the total number of (4q + 2)s and (4r)a components is even.
We will use the Diels-‐Alder reacZon to exemplify the applicaZon of the Woodward-‐Hoffmann rules.
Draw a ‘curly arrow’ mechanism to idenZfy the components.
For the Diels-‐Alder reacZon these are 4π (diene) and 2π (dienophile).
Draw a convincing 3-‐D orbital diagram to show the overlap of the components.
Label the components as supra or antarafacial.
Sum the components according to the Woodward-‐Hoffmann rule.

Draw a ‘curly arrow’ mechanism – this generally allows idenZficaZon of the components.
For the Diels-‐Alder reacZon these are 4π (diene) and 2π (dienophile),
Draw a convincing 3-‐D orbital diagram to show the overlap of the components.
Label the components as supra or antarafacial. Here the diene is being used in a suprafacial manner –
the two new bonds are being formed on the same face of the diene.
The alkene is also being used in a suprafacial manner being used in a suprafacial manner
Sum the components according to the Woodward-‐Hoffmann rule
(4q + 2)s = (4q + 2)s =

(4r)a = (4r)a =
Total = Total =
(4q + 2)s = (4q + 2)s =

(4r)a = (4r)a =
H H
Total = X Total =
Generally simplest to maximise suprafacial components and not subdivide conjugated systems.
[2 + 2] cycloaddiZons
Draw a ‘curly arrow’ mechanism to idenZfy the components – 2π, 2π
Draw a convincing 3-‐D orbital diagram to show the overlap of the components O O
Label the components as supra or antarafacial. heat
Sum the components according to the Woodward-‐Hoffmann rule
O X O
O O
(4q + 2)s =
(4q + 2)s = (4r)a =
(4r)a = Total =
Total =
but geometrically
unreasonable,
(4q + 2)s =
(4r)a = therefore does not
Total = occur
Woodward-‐Hoffmann rule gives you the symmetry allowed orbital overlap but you have to decide whether
the overlap you have drawn is geometrically reasonable.
Nomenclature for suprafacial and antarafacial components.

Suprafacial and antarafacial refer to modes of bond formaZon that are respecZvely on the same face or on
opposite faces of a molecular component.
C H
σ-‐suprafacial
π-‐suprafacial π-‐antarafacial
σ-‐antarafacial
σ-‐suprafacial σ-‐antarafacial ω-‐suprafacial ω-‐antarafacial

Woodward-‐Hoffmann approach for thermal electrocyclic reacZons Me
Draw a ‘curly arrow’ mechanism to idenZfy the components – Me

these are 2π (alkene) and 2σ (single bond) Me
Me
Draw a convincing 3-‐D orbital diagram to show the overlap of the components
Sum the components according to the Woodward-‐Hoffmann rule.
(4q + 2)s = (4q + 2)s =

Me Me (4r)a = (4r)a =
Me Me
Total = Total =
H H H H
(4q + 2)s =
Me Me (4r)a =
Total =
X Me
Me
H H
Thermal ring opening of cyclobutene is conrotatory. Thermal disrotatory opening is symmetry forbidden.
Woodward-‐Hoffmann approach for sigmatropic rearrangements

Draw a ‘curly arrow’ mechanism to idenZfy the components – 2π, 2σ, 2π
Label the components as supra or antarafacial. Me Me
O O
Sum the components according to the Woodward-‐Hoffmann rule. Me Me
O O
O Me
Me Me
Me
(4q + 2)s = (4q + 2)s =
(4r)a = Me (4r)a =
Me Total =
Total =
Claisen rearrangement via chair TS is allowed. Claisen rearrangement via boat TS is allowed.
Woodward-‐Hoffmann rule does not tell us that the chair TS is lower in energy than the boat TS. You need to use your
chemical knowledge/intuiZon to decide that a chair is generally lower in energy than the corresponding boat and that it
is generally more favourable to have equatorial subsZtuents than axial subsZtuents on a chair.
Woodward-‐Hoffmann approach for sigmatropic rearrangements and group transfer

Draw a ‘curly arrow’ mechanism to idenZfy the components
Sum the components according to the Woodward-‐Hoffmann rule. O
O
H H
O O
S O
O Ph SPh O
O
O O
(4q + 2)s = (4q + 2)s =
Ph S Ph S (4r)a = (4r)a =
Total = H H
Total =
[2,3]-‐sigmatropic rearrangement via envelope TS. ene-‐reacZon (group transfer) via envelope TS.
For thermal cycloaddiZons and group transfers:
If the total number of electrons is (4n + 2) both components can be used in a suprafacial manner.
If the total number of electrons is (4n) one of the components is suprafacial and the other antarafacial.
For electrocyclic reacZons:
Thermal electrocyclic processes will be conrotatory if the total number of electrons is 4n and disrotatory if the
total number of electrons is (4n +2).
FronZer Molecular Orbital approach

‘As two molecules approach each other, three major forces operate:
(i)  The occupied orbitals of one repel the occupied orbitals of the other.
(ii)  Any posiZve charge on one a•racts any negaZve charge on the other (and repels any posiZve)
(iii)  The occupied orbitals (especially the HOMOs) of each interact with the unoccupied orbitals (especially the
LUMOs) of the other, causing an a•racZon between the molecules.’ (from Fleming, Molecular Orbitals and Organic Chemical
ReacZons)
FronZer Molecular Orbital considers the interacZon of the Highest Occupied Molecular Orbital (HOMO) and the
Lowest Unoccupied Molecular Orbital (LUMO) to be of overriding importance.
LUMOa empty MOa empty MOb
thermal reacZon
HOMOb
filled MOa filled MOb
For photochemical reacZons one molecule is in the excited state
ψ4 ψ4
ψ3 HSOMO • ψ3 LUMO excited state a ground state b
hν •
• HSOMOa unoccupied MO ψ3
ψ2 • • LSOMO • • • ψ2 HOMO
ψ • • • • • • • • ψ
1 1 LSOMOa occupied MO ψ2
a a* b
ψ12ψ22 ψ12ψ21ψ31
The FMO approach

To apply the FMO method one has to assign a single HOMO and a single LUMO to the reacZon components and see
how they interact.

The FMO approach is simple to apply to reacZons with two components (e.g. cycloaddiZons, electrocyclic ring
opening) but its applicaZon to sigmatropic rearrangements and group transfer reacZons is somewhat contrived.
Assign a single HOMO and a single LUMO to the reacZon
Check to see if there is construcZve overlap between the orbitals
(4q + 2)s =
(4r)a =
Total =
odd ✓
allowed
construcZve overlap ✓ construcZve overlap ✓

The FMO approach Me

Draw a ‘curly arrow’ mechanism to idenZfy the components heat Me
Me
Me
Me H Me H
Me Me
Me
Me
H Me H Me
Me H
(4q + 2)s =
Me H (4r)a =
Total =
odd ✓
allowed
H Me
H Me (conrotatory)

The preference of one conrotatory (or disrotatory) mode is termed torqueoselec+vity (more later).
The FMO approach

hν
Assign a single HSOMO and a single LUMO to the reacZon, (or a single LSOMO and HOMO) –
note a HSOMO has the same phases as the ‘LUMO’ and a LSOMO has the same phases as the HOMO)
Me Me
hν
Me Me
construcZve overlap ✓ H H
(disrotatory)
(4q + 2)s =
(4r)a =
Total =
even ✓
allowed
Me Me photochemically
(disrotatory)

The FMO approach

Me Me
O O
Me Me
O
O O O Me
Me Me Me
Me
Me Me Me
(4q + 2)s =
(4r)a =
Total =
odd ✓
allowed
ψ2 ψ3
HOMO butadiene LUMO butadiene
The FMO approach

S O
Assign a single HOMO and a single LUMO to the reacZon O Ph SPh
O O
O
Ph S Ph S
Ph S
ψ3 ψ3
LUMO butadiene LUMO 4e-‐ allyl O
Ph S (4q + 2)s =
(4r)a =
Total =
odd ✓
allowed
Hücke
Th
matici
Heilbr
Pericyclic Reactions 30 (5) bot
fusion
in a pl
The Möbius-‐Hückel Method atomic
if this
Draw a curly arrow mechanism to assign components bearing
Figure 2. A heptahelicene and its non-superimposable mirror image.
H
clic M
Draw a convincing 3-‐D orbital diagram to show the overlap of the components (easiest to draw be a clo
ψ1 for all components and minimise number of nodes). tron re
Hücke
Count the number of phase inversions in the closed loop of interacZng orbitals – as was pr
counte
always, phase inversions within an (atomic) orbital are not counted. Li
succin
Even number of phase inversions: Hückel topology Zimme
tron st
aromat
Odd number of phase inversions: Möbius topology 4n  e
ergy le
A thermal pericyclic reacZon involving a Hückel topology is allowed when the total along a
number of electrons is (4n +2). electro
tion in
A thermal pericyclic reacZon involving a Möbius topology is allowed when the total separat
number of electrons is 4n. from H. S. Rzepa J. Chem. Ed., 2007, 84, 1535
corolla
ment 1
(For photochemical reacZons the rules are reversed.) Figure 3. Heilbronner’s suggestion for a  Möbius conjugated sys-
tem obtained by  electrons located in molecular orbitals resulting 5.
from 2p atomic orbitals distributed around a Möbius strip bearing
a single half-twist, rather than a planar Hückel ring bearing no
O twist in the orbital basis. 6.
Diels-‐Alder [2 + 2] Ph S Sigmatropic 7.
reacZon cycloaddiZon rearrangement 8.
A
Musuli
inscrib
rules, w
no phase inversions, no phase inversions, no phase inversion system
Hückel system Hückel system Hückel system ure 4).
An
6 electrons 4 electrons 6 electrons comme
allowed ✓ forbidden (thermally)✗ allowed ✓ ing on
the hep
has on
of a pla
The Möbius-‐Hückel Method

Me
A thermal pericyclic reacZon involving a Hückel topology is
Me
allowed when the total number of electrons is (4n +2). Me

A thermal pericyclic reacZon involving a Möbius topology is Me
allowed when the total number of electrons is 4n.
(For photochemical reacZons the rules are reversed.)
Me H
Me H
electrocyclic
reacZons
H Me
H Me
one phase inversion no phase inversions,

Möbus system Hückel system
4 electrons 4 electrons
allowed ✓ forbidden (thermally)✗
(conrotatory) (disrotatory)
Me Me
Me H
H H
H Me
CycloaddiZons
The Diels-‐Alder reacZon is greatly accelerated by having an EDG on the diene and an EWG on the dienophile.

O O
165 °C, 17 h
900 atm H 150 °C, 0.5 h H
OMe O OMe O O O
H 100 °C, 2 h H H 120 °C, 6 h H
MeO MeO
O
‘ortho’ and ‘para’ products predominate.
OMe AlCl3, -‐78 °C H
CO2Me
Lewis acids catalyse the reacZon.
endo
‘endo’ products predominate.
Me O Me O Me
OMe OMe +
OMe
O
without catalysis 90% 10%
with AlCl3 98% 2%
CycloaddiZons
Increase rate of reacZon with EWG on dienophile. ψ4
α -‐ 1.53β
0.66 0.23
An EWG (‘Z’ subsZtuent) on the dienophile lowers the O )0.43 )0.58
energy of the LUMO (and of all orbitals). (HOMO ethene is α + H α -‐ 0.35β
β, LUMO is α – β). LUMO ψ3 )0.23 )0.43
066 )0.58
The best energy match is therefore the HOMO of the diene with α
the LUMO of the dienophile (full double-‐headed arrow) rather than HOMO ψ2
the HOMO of the dienophile with with the LUMO of the diene
0.58 )0.58 α + 1.00β
0.58 0
(dashed double-‐headed arrow).

Catalysis by Lewis acids arises from further lowering of the LUMO
ψ1 0.43
0.66 α + 1.88β
0.23 0.58
of the dienophile.
ψ4
ψ3 O
ψ2
ψ3 LUMO AlCl3
ψ2 • α
O
ψ2 AlCl3
HOMO
ψ1
ψ1
ψ1
O
O
AlCl3
O
CycloaddiZons
ψ4
In a similar manner placing an EDG on the diene raises the energy α – 1.62β
of the HOMO making it a be•er energy match for the HOMO of the 0.37 &0.60 0.60 &0.37
dienophile.
Having an EDG on the dienophile (higher energy HOMO) and an EWG on ψ3 α -‐ 0.62β
the diene (lower energy LUMO) is generally less effecZve at increasing the
late of the Diels-‐Alder reacZon. (Inverse electron demand) 0.60 &0.37 &0.37 0.60
α
ψ5 ψ2 α + 0.62β
ψ4
0.60 0.37 &0.37 &0.60
ψ2 ψ4
ψ3 ψ1 α + 1.62β
ψ3 0.37 0.60 0.60 0.37
α
ψ2
ψ1 ψ2
ψ1
ψ1
OMe
In general:
EWG (Z-‐subsZtuents) lower HOMO & LUMO energies
EDG (X-‐subsZtuents) raise HOMO & LUMO energies
carbon conjugaZng systems e.g. C=C, raise HOMO & lower LUMO
These groups distort orbital coefficients.

CycloaddiZons O
Diels-‐Alder reacZon regioselecZvity α -‐ 1.53β
H ψ4 0.66 0.23
)0.43 )0.58
LUMO ψ3 )0.23 )0.43

α -‐ 0.35β
O 066 )0.58
$0.707 α
0.500 0.500 0.37 $0.60 0.60 $0.37 0.44 $0.65 0.55
HOMO ψ2
0.58 )0.58 α + 1.00β
0.58 0
O LUMO
ψ1 0.43
0.66 α + 1.88β
0.23 0.58
0.707 $0.707 0.60 $0.37 $0.37 0.60 0.65 $0.19 $0.54
O HOMO
ψ4
0.707
0.500 0.500 0.60 0.37 $0.37 $0.60 0.55 0.54 $0.07
&0.60 0.60 &0.37
0.500 $0.707 0.500
O
ψ3
0.37 0.60 0.60 0.37 0.19 0.30 0.30
&0.37 &0.37 0.60
O
0.707 $0.707
AlCl3 ψ2
Coefficients for acrolein just taken as average of allyl 0.37 &0.37 &0.60
caZon and butadiene coefficients – see Fleming. O
AlCl3
ψ1
0.500 0.707 0.500
In the presence of a Lewis acid (e.g. AlCl3) acrolein will 0.60 0.60 0.37
have more allyl caZon character and hence the C-‐terminus
coefficient of the LUMO will be larger. O
AlCl3
CycloaddiZons
ψ5
Diels-‐Alder reacZon regioselecZvity 0.29 $0.50 0.58 $0.50 0.29
0.37 &0.60 0.60 &0.37
ψ4
0.37 &0.60 0.60 &0.37 0.29 &0.50 0.58 &0.50 0.29 0.33 &0.55 0.59 &0.44 0.50 $0.50 0.50 $0.50
0.60 &0.37 &0.37 0.60
ψ3
0.60 &0.37 &0.37 0.60 0.50 &0.50 0.50 &0.50 0.55 &0.44 &0.19 0.55 0.58 $0.58 0.58
0.60 0.37 &0.37 &0.60
ψ2
0.60 0.37 &0.37 &0.60 0.58 &0.58 0.58 0.59 0.19 &0.48 &0.30 0.50 0.50 $0.50 $0.50
0.37 0.60 0.60 0.37
ψ1
0.37 0.60 0.60 0.37 0.50 0.50 &0.50 &0.50 0.45 0.55 0.30 &0.26
0.29 0.50 0.58 0.50 0.29
0.29 0.50 0.58 0.50 0.29 0.15 0.25 0.29 0.25
OMe
CycloaddiZons
Diels-‐Alder reacZon regioselecZvity (Z = EWG e.g. CO2Me; X = EDG e.g. OMe.
HOMO diene / LUMO dienophile is the predominant interacZon

Z X C
Large-‐large and small-‐small overlap is best.
As noted previously, in the presence of a Lewis acid

(e.g. AlCl3) C-‐terminus coefficient of the LUMO of a Z-‐
subsZtuted alkene will be larger leading to increased Z X C
regioseleciZvity in the Diels-‐Alder reacZon.

Z X C
Z X C
Z X C
Z X C
CycloaddiZons
Diels-‐Alder reacZon regioselecZvity (Z = EWG e.g. CO2Me; X = EDG e.g. OMe.
X
OMe O OMe O OMe O Z

H H H
‘ortho’ product
O O O Z
H H H ‘para’ product
MeO MeO MeO X
Z
CN CN
CN CN Z
‘ortho’ product
CycloaddiZons
Diels-‐Alder reacZon the endo rule – endo-‐product is generally the major product with dienophiles containing π-‐
conjugaZng subsZtuents .
O
OMe H CO2Me
not
CO2Me H
Secondary orbital overlap is a decepZvely simple explanaZon for the kineZc preference for the endo-‐
adduct – but has not stood up to high level theoreZcal treatment -‐ sZll a very useful mnemonic.
O O
MeO H H
OMe
endo exo
In cases where the reacZon readily reverses (e.g. Diels Alder reacZons with furan) the thermodynamically
preferred exo-‐adducts are usually obtained.
O O O O
O O
O O
O O
O O
endo-‐kineZc exo-‐thermodynamic
CycloaddiZons
ElectrostaZc arguments have been proposed as a reasonable explanaZon for ‘endo’-‐selecZvity
O H (+) H (+)
OMe H H (+) H (+)

CO2Me
O O
(+) (+)
endo MeO H H
OMe
endo (favoured) exo (disfavoured)

H
Ph
Ph O Ph H H
H H (+)
CHO (+) H
H H
O (+) O
(+) H
H H H
endo
endo (favoured) exo (disfavoured)
Steric effects can favour the exo product. H H
O O H H
Me
H H O
O
Me Me
H Me H
exo
endo (disfavoured) exo (favoured)
OAc O
CycloaddiZons – Drawing stereochemistry for the Diels-‐Alder BF3•OEt2,*50*°C
H
?
O OAc O OAc Me
OAc O
H 1 H H OAc
1 H
OAc
H H H H H CHO
H H 2 6 2 6 CHO
H 3 5
H H 3 5
H Me H Me H Me Me
4
4 Me
H H
endo H H
OAc OAc
H H
H H
O O
H H
H H H H
H H
Me Me
OAc OAc
H H H
H
H H
O O
MeO H MeO H
H H
Me Me
CycloaddiZons
Ketenes undergo (thermal) [2+2]-‐cycloaddiZons with alkenes providing an excellent method for cyclobutane synthesis.
H
H H H H
Cl Cl
Cl Cl
• O Cl O • O O
Cl
Cl Cl
The simplest explanaZon for this reacZon is that the orbitals of the ketene are used as an antarafacial component.
O
(4q + 2)s =
(4r)a =
Total =
odd ✓
allowed
TreaZng the ketene as a vinyl caZon allows a geometrically more reasonable
overlap to orthogonal orbitals
(4q + 2)s =
O O
Cl (4r)a =
Cl O
• R Total =
•
odd ✓
Cl Cl Cl Cl R R R allowed

O
CycloaddiZons
Ketene FronZer Orbitals H
HOMO alkene • O H
H H O
C
C LUMO + 1 LUMO + 1 ketene
O (C=C π*)
O construcZve overlap ✓
C
C LUMO
O (C=O π*) HOMO alkene LUMO alkene
C
HOMO
C (C=C π)
O
O
O
LUMO ketene HOMO ketene

With ketenes it is probable that the low lying C=O π* orbital is involved in the reacZon.
Other cumulated π systems which contain a central sp-‐hybridised carbon atom (e.g. allenes, vinyl caZons)
also readily undergo [2+2] cycloaddiZon.

CycloaddiZons
Ketenes readily react with cyclopentadiene to give cyclobutanes.
O H
• O
Cl H H Cl
O Cl
Cl
O Cl
• O •
H
H H
(4q + 2)s = 1
(4r)a = HOMO diene
Total = construcZve overlap ✓
odd ✓
allowed
With an unsymmetrical ketene, the larger ketene subsZtuent will point away from the plane of the alkene.
RegioselecZvity can be predicted from simple “arrow-‐pushing” arguments (the C=O carbon of ketenes is
very electrophilic), or from looking at FMO coefficients.
In reacZons of unsymmetrical alkenes the less sterically demanding C=O part of the ketene will
be oriented above the larger alkene subsZtuents.
CycloaddiZons
Another possible mechanism is a hetero Diels-‐Alder reacZon followed by a Claisen rearrangement.
O H
• O O
Cl H Cl H Cl
H O
Cl
H
O
O
•
O H
• Cl H
Cl
H O
Cl
(4q + 2)s = 1
(4r)a = 0 construcZve overlap ✓
Cl
Total = 1
odd ✓ H
allowed

Certain ketenes appear to react with cyclopentadiene via both a [2+2] cycloaddiZon, and a [4+2]
cycloaddiZon followed by a Claisen rearrangement mechanism.
Oxyallyl-‐diene
O O
O
(4q + 2)s = 1
O (4r)a = 0
O Total = 1
odd ✓
allowed
construcZve overlap ✓
disrotatory
disrotatory

O
O O
(4q + 2)s = 1
(4r)a = 0
Total = 1
odd ✓
allowed

O
O
Allyl caZon-‐diene
AgBF4
Br
Allyl anion-‐alkene and reverse process

LDA,%45%°C Ph Ph Ph
H
Ph Ph Ph Ph
Ph Ph Ph
H
Ph Ph
(4q + 2)s =
Ph Ph
(4r)a =
Total =
odd ✓
allowed
Ph Ph
Allyl anion-‐alkene (reverse process)
O Ph BuLi O
Ph + PhCO2
O H O
O
O O
O
(4q + 2)s =
construcZve overlap ✓ (4r)a =
ψ3 Total =
odd ✓
LUMO butadiene allowed

Ph
It can be easier to analyse the reverse reacZon.
O O O
Ph Ph O
O O
1,3-‐Dipolar cycloaddiZons.
sp-‐hybridized central atom
Y π4s π2s X Y Z X Y Z X Y Z
X Z
1,3-‐dipole
nitrile ylids nitrile oxides

R R
N N
Cl H B R N B R N O
Cl O H
nitrile imines diazoalkanes
H2N R oxidaZon R
R N NH N N N ArSO2N3 +
R R
R R
alkyl azides
R nitrous oxide
N N N N N N
N N O
X R
1,3-‐Dipolar cycloaddiZons.
sp2-‐hybridized central atom
π4s π2s X
Y Y Y
Y Z X Z X Z
X Z
1,3-‐dipole
azomethine ylids azomethine imines

R
R
N
N NH
carbonyl oxides carbonyl ylids
O O
O
ozone nitrones
R
O N
O O O
Ozonolysis
(4q + 2)s =
O (4r)a =
O O
Total =
odd ✓
O construcZve overlap ✓ O allowed
O
O O
O ψ3
LUMO allyl anion

O
O O
O
O O
O

O C
O O
O O
O O
ψ2 •
O
HOMO allyl anion
Azomethine ylids.
Ph Ph Ph
N EtO2C CO2Et EtO2C CO2Et

H H
EtO2C CO2Et
H H H H
construcZve overlap ✓ (4q + 2)s =

conrotatory (4r)a =
ψ3 Total =
Ph Ph
odd ✓
N CO2Et N CO2Et allowed
CO2Et CO2Et ψ2 conrotatory
•

Ph Ph
ψ1
Ph
EtO2C N CO2Et
Ph Ph
Nitrone cycloaddiZons.
Nitrones are readily formed between aldehydes and subsZtuted hydroxylamines.
The nitrone cycloaddiZon can predominantly HOMOnitrone LUMOdipolarophile, or LUMOnitrone HOMOdipolarophile
depending on the subsZtuents on the dipolarophile.
O
O R O
O N R N
NHOH + R N
R H
R' H R' H R'
R'
Stockman synthesis of histrionicotoxin; J. Am. Chem. Soc., 2006, 128, 12656.
N N N N
H
O OH
HO O
O
NH2OH NC
NC NC
N N N
CN CN O
OH O
CN CN CN
heat 180 °C
NC NC
N N
CN CN
O O
Gin’s Nominine synthesis – J. Am. Chem. Soc., 2006, 128, 8734. Me
H H H N
OH H
Me Me OMe
H H CN O
N H X
N Me
H
N
H
OMe
CN O
H
O
CN CN Me CN
Me Me H OMe
N
OMe OMe
N N H
O O
OMe
H
CN
CN Me
Me Me CN
O H
O
N N
N OMe
OMe H O
Gin’s Nominine synthesis – J. Am. Chem. Soc., 2006, 128, 8734.
H H H
O Cl
Me CN i)#NaBH4 Me CN i)#Bu3SnH,# Me CN
H OMe ii)#SOCl2 H OMe AIBN H OMe
N N N
H H H
i)#DIBAL
ii)#Ph3P=CH2
H H H
H H H
Me Me Na,$NH3, Me
H O H OMe H OMe
H+,$H2O $iPrOH
N N N
H H H
,"MeOH
N
H
H H H H H
H
Me Me Me
H N H H
N O
N N N
H H H
H
H H
Cheletropic ReacZons c.f. ketenes as vinyl caZons
A sub-‐class of cycloaddiZon/cycloreversion reacZons in O

which the two σ – bonds are made or broken to the same atom. O Cl
Cl O
• R
•
O
Cl Cl Cl Cl R R R
+ CO
More important are the reacZons of singlet carbenes π2s

with alkenes which are sterospecific. (4q + 2)s = 1
(4r)a = 0
Side on approach of the carbene is required for Total = 1
conservaZon of orbital symmetry. odd ✓ ω0s
Cl Cl allowed
Cl Cl
π2a O
Me Me
Me Me
Cl
Cl
(4q + 2)s = Cl
Cl
Cl
(4r)a = Cl
Total =
odd ✓
allowed


Cheletropic ReacZons
The other important cheletropic reacZons involve the reversible addiZon of sulfur dioxide to polyenes.
O
(4q + 2)s = 1
SO2 SO2 S O (4r)a = 0
SO2 SO2 Total = 1
heat and heat and odd ✓
pressure pressure allowed
O O
S O S O
O
O
S O S O

Cheletropic ReacZons
With trienes the extrusion process dominates but considering the reverse process the reacZon must be
antarafacial with respect to the triene component.
(4q + 2)s =
(4r)a =
heat heat Total =
SO2 SO2
%&SO2 %&SO2 O odd ✓
S allowed
O
HOMO – lone pair
LUMO
LUMO hexatriene O
S O
S
O O

O O
S
X too strained; ca. 104 Zmes less reacZve than SO2

Cheletropic ReacZons in Synthesis

Steroid synthesis
Me O Me O Me O
Me O O
H H
H H H
SO2
Colombiasin
Me O Me O
Me O OMe Me H O
OMe
OMe MeOMe
H
HO Me HO Me
H H
HO Me O Me
H Me HO Me H O Me
O H
Me O
H H
Me
SO2 Me
Me
Thermal electrocyclic processes will be conrotatory if the total number of electrons is 4n and disrotatory if the
total number of electrons is (4n +2) – this is reversed for photochemical reacZons.
All electrocyclic reacZons are allowed (provided they are are not constrained by the geometry of the product).
Me Me Me
140 °C, 5 h 140 °C, 5 h
Me
Me Me Me Me
(4q + 2)s = (4q + 2)s =

(4r)a = (4r)a =
Total = Total =
odd ✓ Me odd ✓
Me Me Me H
allowed allowed
disrotatory disrotatory
(4q + 2)s = Me Me
Me Me H (4r)a =
H H H
Total =
H H X Me odd ✓
Me allowed
conrotatory
but geometrically constrained

therefore does not occur.
Ph Ph (4q + 2)s =
Me (4r)a =
hν Ph Ph Ph Ph Total =
Me even✓
Me Me
Ph Me Me Me Me allowed
Ph
conrotatory
conrotatory
ψ3
Cyclopropyl caZon / allyl caZon interconversion
Cl Cl Cl
ψ2 •
Lewis acid
low temperature
ψ1
The ionisaZon of cyclopropyl halides and tosylates is a concerted process to give allyl caZons (i.e. discrete
cyclopropyl caZons are not formed).
The reacZon can be viewed as an internal subsZtuZon in which the electrons in a σ-‐bond (HOMO) feed into
the C-‐X σ* (LUMO).
The reacZon is disrotatory and the sense of rotaZon (torquoselecZvity) is specified – this dictates the
geometry of the allyl caZon and can have a large influence on reacZon rate.
X
Cl Cl Cl
Me
Cl
Me (4q + 2)s =
(4r)a =
Total =
H odd✓
H allowed
disrotatory
Me Me
H Me
Cl Cl Cl
H H
Me H H
Me Me H
construcZve overlap ✓ construcZve overlap ✓ construcZve overlap ✓

disrotatory disrotatory disrotatory
Influence on rates – solvolysis in aceZc acid

H H H Me Me H
H OTs Me OTs H OTs Me OTs H OTs H OTs
H H H H H Me
H H Me H Me Me
1 6 133 2 450 37000

Electrocyclic reacZons -‐ pentadienyl systems.

CaZonic -‐ Nazarov reacZon. FeCl3
FeCl3 O O
Me3Si O Me3Si O Me3Si H
FeCl3 H
4π electrocyclic H H H H
H H
ring closure
relaZve configuraZon
O (4q + 2)s = set by pericyclic reacZon
O
(4r)a =
Total =
H H odd ✓
H H
allowed
conrotatory
conrotatory
Thermal Nazarov cyclisaZon is conrotatory; photochemical Nazarov reacZon is disrotatory.
Anionic.
Ph (4q + 2)s =
Ph Ph (4r)a =
Ph
H PhLi Total =
N N N N N N
odd ✓
Ph H H Ph
Ph Ph allowed
Ph Ph Ph Ph
disrotatory
6π electrocyclic
ring closure
Electrocyclic reacZons exemplified – the endiandric acids.

Ph H H Ph H H H H
H
H H CO2Me H CO2Me H
CO2Me H
H CO2Me
H H Ph H Ph
H H H H H H
endiandric acid A endiandric acid B endiandric acid C endiandric acid D
methyl ester methyl ester methyl ester methyl ester
Diels Alder Diels Alder Diels Alder 6π electrocyclic
Ph H Ph H H
CO2Me H H H
H CO2Me H
H CO2Me
Ph CO2Me
H H H Ph
endiandric acid E endiandric acid F endiandric acid G

methyl ester methyl ester methyl ester 8π electrocyclic
6π electrocyclic 6π electrocyclic
H H H H
8π electrocyclic
CO2Me
CO2Me
Ph Ph
CO2Me
Ph CO2Me Ph
Biosynthesis proposed by Black J. Chem. Soc., Chem. Commun., 1980, 902.
BiomimeZc synthesis by K. C. Nicolaou, J. Am. Chem. Soc., 1982, 104, 5558.
H2 Lindlar
HH
CO2Me
CO2Me
CO2Me Ph 8π electrocyclic
Ph
ring closure -‐
Ph
conrotatory
Ph R
H H H
H CO2Me Ph H H
R' H H
H CO2Me 6π electrocyclic CO2Me
ring closure -‐ Ph
heat, 100 °C exo-‐Diels Alder endiandric acid E disrotatory
reacZon
methyl ester 6π electrocyclic R
Ph H ring closure -‐ H H
H
disrotatory
H CO2Me R'
H
H H
H
endiandric acid A endiandric acid D
H Ph H H
methyl ester methyl ester H CO2Me
Ph
H CO2Me
H2 Lindlar
CO2Me
Ph CO2Me
Ph 8π electrocyclic
Ph CO2Me ring closure -‐
conrotatory
R
Ph H
CO2Me Ph H H H H
H
R' H H
H CO2Me 6π electrocyclic
ring closure -‐ Ph
heat, exo-‐Diels Alder CO2Me
endiandric acid F disrotatory
100 °C reacZon methyl ester
6π electrocyclic
Ph H ring closure -‐ R
H H H
CO2Me disrotatory
H
R'
H
H H
endiandric acid B endo-‐Diels Alder

H H H H
methyl ester H reacZon Ph
H H
CO2Me
H H
Ph CO2Me
Ph H H CO2Me
H
endiandric acid C endiandric acid G
methyl ester methyl ester
Sigmatropic rearrangements.
SyntheZcally the most important sigmatropic rearrangements are the Cope and Claisen rearrangements and
variants thereof.
The Claisen/Cope rearrangements can proceed via chair-‐like or boat-‐like transiZon states – the chair-‐like
transiZon state is strongly favoured unless there are steric constraints that force a boat-‐like transiZon state.
Where possible, subsZtuents generally adopt equatorial sites in the chair-‐like transiZon state.
Classical Claisen rearrangement.
[3,3]-‐sigmatropic
R R R’ = H, R
rearrangement
O O tautomerism OH
R'
R'
[3,3]-‐sigmatropic
rearrangement
R
R
O tautomerism
OH
R'
H R'
Claisen and Cope

(4q + 2)s = 3
heat + (4r)a = 0
Total = 3
major minor odd ✓
equatorial allowed
H

H
Me Me
heat
Me Me
H H Me
chair trans, trans -‐ major Me
Me Me
H H H
H H
H
axial chair
Me Me
cis, cis -‐ minor
Me
Me Me Me
H H H
H H
H
Me Me cis, trans
boat cis, trans -‐ trace
Claisen rearrangement -‐ variants.

Johnson-‐Claisen rearrangement -‐ synthesis of γ,δ-‐unsaturated esters. Me
OEt O
OEt
OH O
OEt
OEt
OEt cat.%H%%%%%%heat H
±H+ OEt
OEt equatorial
Me
H OEt OEt OEt
O
OEt H
O O
O
H
Eschenmoser-‐Claisen rearrangement - synthesis of γ,δ-‐unsaturated amides. OEt
MeO
NMe2 NMe2 NMe2
OMe NMe2
O O via
HO OMe
heat
Carroll rearrangement -‐ synthesis of γ,δ-‐unsaturated methyl ketones. Ireland Claisen rearrangement.
O O

LDA$then OSiMe3 OSiMe3
Me3SiCl
O O O
O
OH
OH
then%heat O H3O+
O
Oxy-‐Cope rearrangement.
Generally the Cope rearrangement requires very high temperatures > 200 °C.
R R
heat
The anionic oxy-‐Cope can be conducted at low temperature (0 °C).
OH OH O
k1
oxy-‐Cope
O O O k2/k1 ∼1010 – 1017

K
k2
anionic oxy-‐Cope
Useful method for the synthesis of cis-‐decalins.
H H H
H MeO MeO
O O
O O
MeO MeO H H
Bulvalene -‐ valence isomers interconvert by degenerate Cope rearrangements.

c b
b c
d a
c b a a b c d
a
a c
c a
b b
1,n-‐Hydride shi‹s.
A suprafacial 1,n-‐hydride shi‹ involves the hydrogen moving from one end of the conjugated system to the
other across one face of the conjugated system.
An antarafacial 1,n-‐hydride shi‹ involves the hydrogen moving from one end of the conjugated system to
the other and moving from one face of the conjugated system to the opposite face.
1 suprafacial shi‹ of H 5 antarafacial shi‹ of H
H 6
2 3
4 [1, 5] 4
H
1 7 [1, 7]
5 H
3 1 H
2
1
H H
(4q + 2)s =
(4r)a =
(4q + 2)s = (4q + 2)s = H
Total =
(4r)a = (4r)a = odd✓
Total = Total = allowed
odd✓ odd✓
allowed allowed
1,5-‐Hydride shi‹s occur readily when the two ends of the diene are held close.
Me H Me Me Me Me
0 °C H H
H H
H H
H H
In acyclic systems 1,5-‐hydride shi‹s can be much slower.
Me H H tBu tBu
O
tBu Me Me H
D
Ph Ph HO
Ph D D D chiral aceZc acid
H T
T T T
H
tBu Me
Ph Ph
D Me tBu
T D T
H
200 °C
[1,5]-‐hydride shi‹
H
T D Me tBu
1,2-‐Shi‹s of alkyl groups can also be pericyclic.

R (4q + 2)s =
CarbocaZons readily undergo allowed 1,2-‐shi‹s.
(4r)a =
R R R Total =
R odd✓
R R R
R allowed
Allowed, concerted 1,2-‐shi‹s of carbanions are geometrically impossible. (4q + 2)s =
(4r)a =
R Total =
R R even✗
R
R
X R R forbidden
R
R
1,2-‐Shi‹s of carbanions occur by a radical mechanism – 1,2-‐Wixg, 1,2-‐Stevens and related
rearrangements.
1,2-‐Wixg rearrangement. Me
X • Me
Me
Me • Me •
Me BuLi
O O O O OH
•
Thermal [1,3]-‐alkyl shi‹s occur with inversion of configuraZon in the migraZng group.
(4q + 2)s =
(4r)a =
1,3-‐alkyl Total = H
3 1 AcO AcO
2 shi‹ odd✓ H D
H AcO D allowed
AcO 1
H
H D D H
AcO H
Thermal 1,3-‐shi‹ of hydrogen is only geometrically reasonable in a suprafacial H
sense which is thermally disallowed.
H
D
(4q + 2)s = H
1 H antarafacial shi‹ allowed
(4r)a =
Total = but geometrically unreasonable
H 1 2
3
even✗
forbidden LUMO π
H H
In the following [1,4]-‐shi‹, migraZon occurs with inversion of configuraZon with D always on the concave
face of the bicyclic structure.
D H (4q + 2)s = D H
D H
D (4r)a =
H Total =
3 4 1
odd✓
allowed
2
1
1,5-‐Alkyl shi‹ with retenZon of configuraZon in the migraZng group. H
H H (4q + 2)s =
heat (4r)a =
[1,5] Total =
[1,5] odd✓
allowed
A number of [2,3]-‐sigmatropic shi‹s are useful syntheZcally. Ar

[2,3]-‐Wixg rearrangement – most likely proceeds via an envelope transiZon state; (4q + 2)s =
large groups at the allylic posiZon will tend to occupy a pseudo-‐equatorial posiZon. (4r)a =
O
Total =
Ar BuLi Ar [2,3] Ar odd✓
O O O allowed
Sommelet-‐Hauser rearrangement.
N
NMe2 Me NMe2
[2,3]
tautomerism
Meisenheimer Rearrangement.
O NMe2
N [2,3] O
R R
Rearrangement of allyl sulfoxides, sulfinimines and sulfonium ylids.
[2,3]
X = O, NTs, CH2
S X
X Ph SPh
A [9,9]-‐sigmatropic shi‹.
1 1
H2N NH2 NH2 NH2 (4q + 2)s =
(4r)a =
2 3
[9,9] Total =
4 H2N NH2 odd✓
5
6 allowed
7
8
9 9
H H
H2N H2N
H2N H2N
Group transfer reacZons.

Group transfer – appear to be a mix of a sigmatropic rearrangement and a cycloaddiZon. (4q + 2)s =
They are bimolecular and so are not sigmatropic rearrangements, and no ring is formed so (4r)a =
they are not cycloaddiZons. Total =
Alder ene reacZon odd✓
H
O O allowed
H 230 °C OMe
OMe H
O O H
H AlCl3 OMe
OMe
25 °C
HOMO σ + π
Conia-‐ene reacZon.
H
O O O CH3
350$°C ene
tautomerise
Carbonyl-‐ene reacZon -‐ frequently catalysed by Lewis acids.
OH
O CO2Me
CO2Me MeO2C OH
CO2Me CO2Me CO2Me
180 °C, 48 h 92 8

SnCl4, 0 °C 2.5 97.5
OH
CO2Me Thermal carbonyl ene reacZon, sterics
CO2Me
H CO2Me are important.
O CO2Me
SnCl4
O CO2Me
H In the Lewis acid-‐catalysed reacZon significant posiZve
CO2Me charge develops in the “eneophile”.
MeO2C OH
CO2Me
Retro-‐ene and retro group transfer reacZons are common.

MeS
R O
S MeS X H heat
heat + R O
O H S X H
+
O H
retro-‐ene retro group transfer: X = S, Se, or NR (Cope eliminaZon)
Pericyclic reacZon summary:
Four classes:
CycloaddiZons (chelotropic reacZons); Electrocyclic reacZons; Sigmatropic rearrangements; Group transfer.
Woodward-‐Hoffmann rules:
A ground state pericyclic reacZon is symmetry allowed when the total number of (4q + 2)s and (4r)a
components is odd (q and r must be integers).
A pericyclic change in the first electronically excited state (i.e. a photochemical reacZon) is symmetry-‐
allowed when the total number of (4q + 2)s and (4r)a components is even.
For thermal cycloaddiZons and group transfers:

If the total number of electrons is (4n + 2) both components can be used in a
suprafacial manner.
If the total number of electrons is (4n) one of the components is suprafacial and the
other antarafacial.
For electrocyclic reacZons:
Thermal electrocyclic processes will be conrotatory if the total number of electrons is
4n and disrotatory if the total number of electrons is (4n +2).

Pericyclic Reactions 6 Lectures, Year 3, Michaelmas 2014: Jonathan - Burton@chem - Ox.ac - Uk

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Pericyclic Reactions 6 Lectures, Year 3, Michaelmas 2014: Jonathan - Burton@chem - Ox.ac - Uk

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Pericyclic Reactions 1

The nature of pericyclic reac>ons

SN2 reacZons are concerted and have no intermediate

In ionic reacZons the curly arrows idenZfy where the

Pericyclic ReacZons – four classes.

Sigmatropic rearrangements – Unimolecular isomerisa>ons which formally involve the

Cope rearrangement Claisen rearrangement

Alder-­‐ene -­‐ reac>ons

Hückel Molecular Orbital Theory for Linear π-­‐systems.

To draw a molecular orbital diagram:

ethene allyl butadiene pentadienyl hexatriene

ψ6 5 α -­‐ 1.80β %0.418 %0.521 %0.232

ψ5 4 α -­‐ 1.25β &0.521 0.232 0.418

ψ4 3 α -­‐ 0.45β &0.232 0.418 &0.521

Draw bare bones of reacZon.

IdenZfy orbitals undergoing change.

Draw sensible approach of substrates.

Construct orbital correlaZon diagram connecZng orbitals

In the Diels-­‐Alder reacZon a plane of symmetry, ψ2

CorrelaZon diagram for [2+2] cycloaddiZon of alkenes

IdenZfy orbitals undergoing change (curly arrows tell us σ2 σ2

Construct orbital correlaZon diagram connecZng orbitals π2

CorrelaZon diagram for electrocyclic reacZons

There are two modes of opening – conrotatory or disrotatory

CorrelaZon diagram for electrocyclic reacZons.

Draw a ‘curly arrow’ mechanism to idenZfy the components.

Label the components as supra or antarafacial.

Sum the components according to the Woodward-­‐Hoﬀmann rule.

(4q + 2)s = (4q + 2)s =

(4q + 2)s = (4q + 2)s =

Nomenclature for suprafacial and antarafacial components.

σ-­‐suprafacial σ-­‐antarafacial ω-­‐suprafacial ω-­‐antarafacial

Woodward-­‐Hoﬀmann approach for thermal electrocyclic reacZons Me

Draw a ‘curly arrow’ mechanism to idenZfy the components – Me

(4q + 2)s = (4q + 2)s =

Woodward-­‐Hoﬀmann approach for sigmatropic rearrangements

Woodward-­‐Hoﬀmann approach for sigmatropic rearrangements and group transfer

FronZer Molecular Orbital approach

LUMOa empty MOa empty MOb

The FMO approach

construcZve overlap ✓ construcZve overlap ✓

The FMO approach Me

The FMO approach

The FMO approach

The FMO approach

LUMO butadiene LUMO 4e-­‐ allyl O

Diels-­‐Alder [2 + 2] Ph S Sigmatropic 7.

reacZon cycloaddiZon rearrangement 8.

The Möbius-­‐Hückel Method

one phase inversion no phase inversions,

H 100 °C, 2 h H H 120 °C, 6 h H

(dashed double-­‐headed arrow).

These groups distort orbital coeﬃcients.

LUMO ψ3 )0.23 )0.43

0.29 0.50 0.58 0.50 0.29 0.15 0.25 0.29 0.25

HOMO diene / LUMO dienophile is the predominant interacZon

As noted previously, in the presence of a Lewis acid

OMe O OMe O OMe O Z

OMe H H (+) H (+)

endo (favoured) exo (disfavoured)

Steric eﬀects can favour the exo product. H H

LUMO ketene HOMO ketene

Allyl anion-­‐alkene and reverse process

Alder-‐ene -‐ reac>ons

Hückel Molecular Orbital Theory for Linear π-‐systems.

ψ6 5 α -‐ 1.80β %0.418 %0.521 %0.232

ψ5 4 α -‐ 1.25β &0.521 0.232 0.418

ψ4 3 α -‐ 0.45β &0.232 0.418 &0.521

In the Diels-‐Alder reacZon a plane of symmetry, ψ2

Sum the components according to the Woodward-‐Hoﬀmann rule.

σ-‐suprafacial σ-‐antarafacial ω-‐suprafacial ω-‐antarafacial

Woodward-‐Hoﬀmann approach for thermal electrocyclic reacZons Me

Woodward-‐Hoﬀmann approach for sigmatropic rearrangements

Woodward-‐Hoﬀmann approach for sigmatropic rearrangements and group transfer

LUMO butadiene LUMO 4e-‐ allyl O

Diels-‐Alder [2 + 2] Ph S Sigmatropic 7.

The Möbius-‐Hückel Method

(dashed double-‐headed arrow).

Allyl anion-‐alkene and reverse process

Allyl anion-‐alkene (reverse process)

A sub-‐class of cycloaddiZon/cycloreversion reacZons in O

Electrocyclic reacZons -‐ pentadienyl systems.

endiandric acid B endo-‐Diels Alder

Claisen rearrangement -‐ variants.

Useful method for the synthesis of cis-‐decalins.

Bulvalene -‐ valence isomers interconvert by degenerate Cope rearrangements.

1,2-‐Shi‹s of alkyl groups can also be pericyclic.

A number of [2,3]-‐sigmatropic shi‹s are useful syntheZcally. Ar

Carbonyl-‐ene reacZon -‐ frequently catalysed by Lewis acids.

Retro-‐ene and retro group transfer reacZons are common.