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