Pericyclic Reactions

© Macquarie University, 2012

CBMS304/CBMS804; Advanced Organic and Biological Chemistry B, Topic 2

Pericyclic Reactions No intermediates No electrophile or nucleophile Rate not dependant on solvent Two or more bonds are broken simultaneously Catalysed by light or heat Are reversible


Pericyclic ReactionsPericyclic Reactions

no electrophile?no nucleophile?no intermediate?

high stereoselectivity

electrocyclicreactions

1 new σ-bondσ1 leσσ π-bondσ

ring cloσing:HOMO of π

ring oπening:HOMO of σ, LUMO of π

diσrotatoryconrotatory

thermal πhotochemical

sigmatropicrearrangements


bondσ σhifted

H-σhiftC-σhift

HOMO of σ, LUMO of π

σuπrafacial antarafacial


MAP FOR 331CONCEPT

cycloadditions2 new σ-bondσ2 leσσ π-bondσ

[4n + 2]π electronσ

[4n]π electronσ

σecondary orbital overlaπ= exo or endo TS

πhotochemicalthermal

HOMO + LUMO

regioσelectivity baσedon electronegativity


Bonding in carbon compounds

Valence bond model Equates covalent bonds with the sharing of two electrons

Thus H should form 1 bond and O 2 etc.

1s

2s

2p { Lewis rule of eight Lewis rule of eight Aufbau principleAufbau principlePauli exclusion principlePauli exclusion principle


Valence Bond Theory

Thus Oxygen should form two bondsAnd Nitrogen three bondsBut why does carbon form four bonds?

O N

H

HHHH


Hybridisation

Carbon should form two bonds but it usually forms four

sp3

CCH

H

H

H


Pauling theory of hybridisation

Mathematical combination of s and p orbitals gives sp3 hybrids

This explains four equivalent bonds and tetrahedral geometry

+ 3 4

sp sp3


Does H2+ exist? Correlation Diagrams

H:H H.H+ ?• Rule #1: Conservation of Orbital Number

H.H+H HH:H


Why is O2 paramagnetic?

Rule #2: Sigma (σ) Orbitals are Always the Lowest Energy [and Sigma* (σ*) the Highest]

Rule #3: pi (π) Orbitals are Higher in Energy than σ but pi* (π*) are Lower than σ*

O O

O

2p2p

O

O O••


Ethylene (or is it ethene)?

Rule #2: Sigma (σ) Orbitals are Always the Lowest Energy [and Sigma* (σ*) the Highest]

Rule #3: pi (π) Orbitals are Higher in Energy than σ but pi* (π*) are Lower than σ*

C

sp2sp2

C

π

σ

σ

π

C CH

H

H

H

LUMO

HOMO


Frontier Molecular Orbitals

Highest Occupied Molecular Orbital (HOMO) andLowest Unoccupied Molecular Orbital (LUMO)

are the orbitals that can either donate or receive electrons from another molecule and thus are the most important

The HOMO of one reactant interacts with the LUMO of the otherie a filled orbital of one and an empty orbital of another are the closest in energy


NH3 + H-Cl NH4Cl

Is something as simple as the reaction of ammonia with hydrochloric acid describable with a correlation diagram?

NH3 HCl

σ*n

NH4+

sp3

HOMO

LUMO


Reaction of ethylene and bromineThe HOMO of ethylene is the π-bondThe LUMO of Bromine in the σ* orbital

π

σ

σ

π

LUMO

HOMO

σ

σLUMO

HOMO


Guidelines to Constructing Molecular Orbitals in Conjugated Systems

With n p-orbitals you get n -orbitals (Rule #1) The energy of the -orbital increases with the number of nodes

(Rule #5) Nodes MUST be symmetrically placed Bonding (π) orbitals have energies less than an isolated p-orbital Non-bonding (n) orbitals have the same energy as an isolated p-

orbital Antibonding (π*) orbitals have greater energy than an isolated p-

orbital Rotation (or reflection) about the centre of the conjugated system

produces an image with phases reversed (A) or the same (S)


The Allyl system

A

S

A0

2

1

nodes

QuickTime™ and aGIF decompressorare needed to see this picture.


QuickTime™ and aGIF decompressorare needed to see this picture.π

π*

n

Bonds

–2

0

+2


The Butadiene systemC2

S

A

S

A

mirror

A

S

A

S


The Cyclobutadiene SystemBonds

–3

–1

+1

+3

Bonds

–4

0

+4

Nodes

3

2

1

0

Nodes

4

2

0


The Cyclohexatriene SystemBonds

–5

–3

–1

+1

+3

+5

Nodes5

4

3

2

1

0

Nodes Bonds6 –6

4 –2

2 2

0 6

A

S

A

S

A

S

A

S A

S A

S


Pericyclic reactions

Concerted reactions proceed with no intermediate E.g. SN2 reactions

C Br

H

H H

HO–

C Br

H

H H

HO CHO

H

HHBr–

Pericyclic reactions are concerted reactions with a cyclic transition state


Examples Cycloadditions

1,-3-dipolar additions

Electrocyclic reactions

Sigmatropic rearrangements

OO

O

O

O

O

O

O

+Δ

O

O

O

OH

H

hn

Ph N N NΔ

NN

N

Ph

O OHΔ


Cycloadditions





HOMO + LUMO




Cycloaddition Reactions: Mechanism

The simplest example is the photolysis of ethylene: A [2π+2π]-cycloaddition

1. Arrow pushing

Electrons can go either way



Consider two ethylenes approaching each other and the π-orbitals slowly become σ-orbitals



2. Correlations Diagrams 2 π-bonds are converted to two σ-bonds

π

π

σ

σS S

A A

S A

A S



2. Correlations Diagrams Photochemically allowed: Excited state goes to excited state

π

π

σ

σ


Cycloadditions: Mechanism

3. Frontier Molecular Orbital (FMO) approach

π

π HOMO

LUMO

X

HOMOLUMO


Cycloadditions: [4π+2π]-Cycloaddition

Also known as the Diels-Alder reaction Involves a 4-electron system (diene) andA 2-electron system (dienophile)3 π-bonds become 2 σ-bonds and one new π-bondNeed to consider only the orbitals that change.



Also known as the Diels-Alder reaction

π1

π2

π2

π1

m1

A

S

A

S

A

S

S A

A

S

S A



FMO model

π1

π2

π2

π1

LUMO

HOMO

LUMO

HOMO

LUMO

HOMO

HOMO

LUMO



Aromatic TS Rule Add up the number of electrons involved in the transition

state (TS) If the TS is aromatic then the reaction is thermally allowed (4n+2) electrons is the magic number because it allows

electron delocalisation and REDUCTION in overall energy


Secondary Effects: Secondary Orbital Overlap

Notice that in the Diels-Alder reaction the dienophile approaches the diene from one face: Suprafacial.




What happens if the dienophile is more than just an alkene? For the dimerisation of cyclopentadiene, you can have endo

or exo attack

exo endo



The two orientations end up with different stereochemistries

exo

endo

H

H

H

H



Frontier molecular orbital analysis

π1

π2

π2

π1

LUMO

HOMO

exo

endo


DNA damage; an example of [2π+2π]-cycloaddition

Two thymidine bases can react when one is excited photochemically.

HN

N N

NH

O O

O O

HN

N N

NH

O O

O OH H

280 nm

240 nm


Not all cycloadditions are endo

[6π+4π]-cycloadditions

O O

O O

Exo

EndoX


Secondary effects: Regioselectivity

If the diene and dienophile are substituted many products are possible

OCH3

OHCOCH3

OCH3

CHOOCH3

CHO

OCH3

CHOCHO



[4π+2π]-cycloaddition, therefore thermally allowedAldehyde has a double bond that is conjugated with

the dienophile so it is really a diene tooSubstituents on the diene and dienophile can

polarise the pi-system to favour one orientation over another



Resonance effects can explain the regioselectivity

OCH3

H

O

OCH3

H

O

OCH3

H

O

OCH3

H

O



Secondary orbital overlap explains the stereoselectivity

OH

OHH3CO H3CO

HOMO

LUMO



Only one product is formed

OHC

OCH3

OCH3

CHO

OCH3

CHO

OCH3

CHO

OCH3

CHO

OHC

OCH3

OCH3

CHO

OCH3

CHO

OCH3

CHO

OCH3

CHO

OHC

OCH3

OCH3

CHO

OCH3

CHO

OCH3

CHO

OCH3

CHO


1,3-dipolar addition

Another example of [4π+2π]-cycloaddition



Correlation diagram is constructed as usual

π

π

σ σ1

n

σ σ1

S

A

A

S

S

S A

S

S A



FMO analysisTake the HOMO and LUMO of two reactantsSee if the orbitals overlap constructively or not

anion

HOMO

LUMO

cation

HOMO

LUMO



Ozonolysis of an alkene is an example of 1,3-dipolar addition

The malozonide is the product of the addition which quickly rearranges to the ozonide

OO

OO

O O O

OOOO O

malozonide


Larger rings

Explain the following reaction: 1. Draw arrows to explain the mechanism 2. Use frontier molecular orbitals to determine if the

reaction is allowed or forbidden 3. Identify the HOMO and LUMO of each reactant 4. Does the HOMO of one overlap with the LUMO of the

other in a constructive fashion?

Δ


Larger rings

LUMO of the hexatriene has 3 nodesHOMO of alkene has none

Δ LUMO

HOMO


Larger rings

For larger rings, the ends can be flexible

Δ

suprafacial antarafacial


SummaryCycloadditions involve the conversion of two π-

bonds to two σ-bondsThey can be allowed (thermal) or forbidden (requires

electronic excitation of one reactant)Allowed reactions involve [4n+2] electronsPhotochemical reactions require [4n] electronsExo and Endo products are determined by

secondary orbital overlapRegiochemistry is determined by electronic effectsReactions are typically suprafacial but larger rings

can react in an antarafacial way


Summary

Adding two more electrons reverse the rules Catalysing with UV-light reverses the rules Going from suprafacial to antarafacial reverses the rules


Summary








HOMO + LUMO











bondσ σhifted

H-σhiftC-σhift





Electrocyclic Reactions












bondσ σhifted

H-σhiftC-σhift





Electrocyclic Reactions

Involve the conversion of two π-bonds into a σ-bond and a new π-bond

What happens if the butadiene is substituted? If this is like the other pericyclic reactions the reaction should go with stereospecificity


Cycloaddition Reactions

The reverse reaction (ring opening) is possible because it is an equilibrium system

RR

H

H

R

R

H

H

trans

cis

Conrotatory

RR

H

H

H

R

H

R

cis

cis

Disrotatory


Disrotatory vs Conrotatory

Look at the reaction in more detail

Disrotation

Conrotation

mirror

axisof

rotation

Disrotatory Conrotatory


Conrotatory and Disrotatory

QuickTime™ and aGIF decompressor

are needed to see this picture.

QuickTime™ and aGIF decompressor

are needed to see this picture.


Disrotatory Correlation Diagram

RR

H

H

RR

H

H

RR

H

H

RR

H

H

R

H

R

H

R

H

R

H

R

H

R

H

R

HH

energy

S

S

A

A

S

A

S

A

R

Thermally forbidden


Conrotatory Correlation Diagram

Thermally allowed

RR

H

H

RR

H

H

RR

H

H

RR

H

H

R

R

H

H

R

R

H

H

R

R

H

H

R

RH

energy

S

A

S

A

A

S

A

S

H


R

R

H

H

FMO approachR

R

H

H

R

R

H

H

R

R

H

H

R

RH

H

HOMO

HOMO

LUMO RR

H

H


Biosynthesis of vitamin D

An example of a biological electrocyclic reaction

HO

HO

H H

H

HO

H H

ergosterol lumisterol

previtamin D3

hn

hn



Looking at just the reacting ring

H

H HHHOMO

LUMO

H



Provitamin D2 is converted spontaneously to vitamin D

HO

H

provitamin D2

HO

H

vitamin D2


Sigmatropic Rearrangements








HOMO + LUMO











bondσ σhifted

H-σhiftC-σhift






Nomenclature

1

2

3

1'2'

3'

12

3

1'2'

3'

One sigma bond is destroyed and a new one made


1

2

3

1'2'

3'

12

3

1'2'

3'


Nomenclature, [3, 3]-sigmatropic shift


Cope Rearrangement

HOMO of σ and LUMO of π-bonds

HOMOLUMO

LUMO


Name this reaction

HOMO

LUMO

123

4

5

1'

6

new π-bond

new σ-bond


Charged species

Name this sigmatropic rearrangement

O

Ph

O

Ph

base

O

Ph

1

2

3

1'2'



Provitamin D2 is converted spontaneously to vitamin D

HO

H

provitamin D2

HO

H

vitamin D2

H


[1,7]-migrations should be forbidden

So why does it proceed spontaneously in the biosynthesis of vitamin D?

suprafacial antarafacial

HOMO

LUMO


Last silde

How many peaks does this compound have in its 1H NMR spectrum?

Macquarie University

Where is Macquarie University???

Sydney, Australia

Pericyclic Reactions

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