Pericyclic Reactions II

HO

O

O

H

O

O

O

Alder ene reaction

Cycloaddition Reactions

Cycloaddition reactions

[2+2]Ene Reaction,Thermal,

Photo

[4+2]Diels-Alder Reaction

1,3 dipolar C.AAlkene(2π) +Nitrone 2e

Cycloaddition Reactions

• In this reaction two π bond lost and two σ bonds formed

• One step mechanism, no intermediates (aromatic transition state*) arrows start from π bond and go around the ring.

• Can occur thermally or photochemically.

• All cycloaditions are suprafacial ( occur on one face of π system).

Suprafacial and antarafacial geometries

• SuprafacialSuprafacial if overlap occur at two lobes located on the same side the nodal plane

• Antarafacial Antarafacial if on opposite sides

Ene Reaction• Alder Ene reaction• Alkene with –I group (enophile) and alkene with allylic

hydrogen.• Formation of one new C-C and C-H bonds• No ring formed here ????????• Mainly , similar features of D.A reaction.

H

O O

H

O

O

O

O

Woodward – Hoffmann rulesWoodward – Hoffmann rules

Total number of (4q + 2)s and (4r)a

Reaction conditions

Allowed mode of ring closure

Odd number Thermal Suprafacial

Odd number Photochemical Antarafacial

Even number Thermal Antarafacial

Even number Photochemical Suprafacial

For Cycloadition reactions

Enophiles

• Can also be aldehyde, ketone and imines.• The product in this case is hydroxylated.

R2 R1R2 R1 R2 R1 R3 R1

O S N R2R4

R3

H

H

X

O

X

O

Ene Reaction

• Can be catalyzed by Lewis acids to increase electrophilicity of enophile.

• Intramolecular ene reaction

O

H

MeAlCl2O

HO

R

OH

R

Carbonyl Ene Reaction• Carbonyl compounds are good enophiles.• L.A catalysis is possible (lowering LUMO energy)• Using L. A enhances stereoselectivity.

MeO

O

MeO

OH

O O

HL.A

Diels-Alder Reaction

• Method for synthesis of 6-membered ring• One-step, concerted reaction• Termed [4+2] cycloaddition reaction where 4 and 2 electrons react.

+                                

Otto Diels Kurt Alder

Diels-Alder Reaction

• Discovered by O. Diels and K. Alder in 1928.• Occur between a conjugated diene and substituted alkene

(dienophile) to form cyclohexene ring system.

• Concerted reaction (single step), can be accelerated by heating or using some catalysts.

• [ 4+2 ] cycloaddition reaction.

• In retro Diels-Alder reaction, the six membered ring is break down to regenerate the diene and dienophile using high temperature usually.

• Stereoselective reaction ( mainly one product formed).

Diels-Alder Reaction

• Stereospecific reaction ( reactants can keep their stereochemistry).

• No transition states or charged intermediates.

• All electrons moving in same time to form two new σ bonds.

• 100 % economic ( No. of reactants atoms = No. of products atoms).

• If one or more of diene or dienophile atoms are not carbon ,the reaction is hetero-Diels-Alder reaction.

How it works?

• Concerted reaction via aromatic transition state.

• There are two approches, the first depends on the interaction between HOMO of The diene and LUMO of the dienophile.

• The second, depends on +I, -I groups affect, since they form negative and positive cherges on the diene and dienophile.

Bonding

Antibonding

HOMO

LUMO

AB

A B

Suprafacial

ψ1

ψ2

ψ3

ψ4

Ψ2׳

ψ1׳ ψ2

Ψ2׳

ψ1׳

ψ3

Frontier orbital interactions in the[π4s+π2s] cycloaddition

Photochemical [2+2] Cycloaddition

• 4n cycloaddition type (not allowed thermally). • Light excitation• Stereospecific reaction• Forward reaction

Bonding

Antibonding

HOMO

LUMOHOMO LUMO

*

ψ2

ψ2׳

ψ2ψ2׳

Photochemical [2+2] Cycloaddition

O O

.hv

O

.

CO2Me

CO2Me

O O OCO2Me

CO2Me

MeO2C

MeO2C

hv

• Mechanism of most of theses reactions are not clear due to isomerisation.

Regioselectivity

O O

hv

O -

hvX

O

+

• LUMO - LUMO Interaction

• HOMO - LUMO Interaction

Thermal [2+2] Cycloaddition• Mainly, via ketene chemistry.

• Formation four memebered ring.

• Alkene with elecrtophilic alkene

C

Oheat

C

O

C

NR

OC

ClCl

Frontier orbital interactions in the[π2s+π2s] cycloaddition

A- Thermal reaction

Bonding

Antibonding

HOMO

LUMO

Suprafacial Antarafacial

ψ1

ψ2

ψ1

ψ2

Thermal [2+2] Cycloaddition

• Cyclopentadiene can react in [2+2] fashion??? faster than Diels-Alder.

C

O

OAcNC

O

NO2

NO2

CNOAc

1,3 dipolar cycloaddition• [(2╥ +2e) + 2 ╥ ] to form five membered ring

• 1,3 dipolar component and polarophile (substituted alkene).

• Nitrone ( 3 atoms ) + Alkene (2 atoms).

• 4s+2s suprafacail cycladdition

ON

R_+

OR

ON

R

1,3 dipolar cycladdition

• [2+3] means no. of atoms NOT [2+3] cycloaddition • Other examples of 1,3 dipoles• Could we say nitrone similar to the diene ???

Comparison

• 1.3 dipolar C.A

• Nitrone and alkene

• [(2╥ +2e) + 2 ╥ ]

• 3+2 =Five membered ring

• Works with simple alkene

• Use HOMOs or LUMOs, depending on the polarophile

• Diels-Alder reaction

• Diene + alkene• [4╥ + 2 ╥ ]

• 4+2= six membered ring

• HOMO of diene and LUMO of the alkene.*

1,3 dipolar cycloaddition

R

ON

R_+

OR

ON

R_+LUMO

HOMO

HOMO

LUMO

Ozonolysis

• Cleveage of alkenes with ozone to form carbonyl compounds mainly.

• So, 1,3 dipolar cycloaddirion

O O

O

O OO

Ozonolysis

• The product can be controlled by work up step.

Ozonolysis

O OO

R1 R2

O OO

R2R1

O

R1

O

R2

O

O

R2

O

O

R1

O

OO

R2

R1

O

OO

R2

R1 SMe2O

R1O

R2S

O

MeMe

Ozonide carbonyl oxide

unstable

1,3 dipolar cycloaddition

1,3 dipolar cycloaddition

Oxidation with OsO4

• OsO4, is yellow solid,used as oxidizing agent and as a catalyst.

• High compatibility for compexation due to multi oxidation states.

• Os (76e) has 11 different oxidation states,.

R

R OsO4

HO

OHR

R

O OOs

OO

Mechanism

R

R

O O

Os

OO

O OOs

R2R1

OO

HO OH

Os

OO HO OH

R2R1

O OOs

R2R1

OO

H2O

Osmate ester

RR

OH

OH

viii

vi Syn

Oxidation with OsO4

• OsO4 can react with both –I ,+I alkenes

• So, it uses HOMO or LUMO*.

• Because of its toxicity and expense, its used with catalytic amount with co oxidant.

OsO4, NMO

t-BuOH, H2O

OH

OH N

O

OMe

References

• Organic chemistry; Clayden, J.; Greeves, N.; Warren, S.;

Wothers, P. Oxford University Press, Oxford, 2006. • Strategic Applications of Named Reactions in Organic

Synthesis; Korti, L.; Czako, B. Elsevier Press, USA, 2005.

• Wikipedia.co.uk.• Organic Chemistry Portal.Org