Quick Reference to

Pericyclic Reactions and Photochemistry

Claude Legault

Litterature Meeting

December 13th, 2004

Goal of the Presentation

Not a course, not a litterature meeting...

Small review of orbital symmetry rules

Simple tricks to determine permitted and forbidden processes

Classify Pericyclic Reactions into main classes

Explain the basics of photochemistry

Definition of the Pericyclic Reactions

Definition Concerted reactions going through a cyclic transition state

Types

1. Cycloaddition (Diels-Alder, [3+2]-cycloaddition, ene reactions)Reactions with the formation of two sigma bonds between the extremity of twopi systems. (ene impliquates a sigma system)

2. Cheletropic reactionsFormation or breakage of two sigma bond between the extremity of a pi systemand one atom

3. Electrocyclic rearrangmentsFormation or breakage of a sigma bond between the extremity of one pi system

4. Sigmatropic rearrangments[1,j] : Migration of an atom along a pi system[i,j] : Migration of a sigma bond between two pi systems

5. Dyotropic rearrangmentsSimultaneous intramolecular migration of two sigma bonds

Simplist View of Polyenes systems

Ψ1

Ψ2

Ψ3

Ψ4

S

A

S

A

S : SymmetricA : Antisymmetric

S

A

S

A

So a first simple thing to remember:

4n+2 (2,6,10,...) electrons polyenes: The HOMO will be symmetric4n (4,8,12,...) electrons polyenes: The HOMO will be antisymmetric

This is general...

Ψ1

Ψ2

Ψ3

Ψ4

First Trick : SUPRA and ANTARA Nomenclature

Suprafacial Rxn happening on the same side of the pi system

Antarafacial Rxn happening on the opposite sides of the pi system

Suprafacial + Suprafacial = SUPRASuprafacial + Antarafacial = ANTARAAntarafacial + Suprafacial = ANTARAAntarafacial + Antarafacial = SUPRA

4n+2 electrons processes (2,6,10,14...) Only SUPRA permitted thermally4n electrons processes (4,8,12,16...) Only ANTARA permtted thermally

When two pi systemsreacts in a cycloaddition

Examples: [π2s+π2s] : 4 electrons SUPRA process -> Forbidden[π4s+π2s] : 6 electrons SUPRA process -> Permitted

[π6s+π4s] : 10 electrons SUPRA process -> Permitted

?

DA and HDA and Definitions

Intermolecular

IntramolecularLevel 1

IntramolecularLevel 2

Diels-Alder relates only to [π4s+π2s]

An Insight in the DA Process (Correlation Diag)

S

S

S

A

A

A

A

S

S

A

A

HOMO dienophile

LUMO dienophile

LUMO diene

HOMO diene

S

E

1 + 2

1 - 2

Rxn coord.

EWG

EWG EWGEWG

Spino, C. et al. Angew. Chem., Int. Ed. 1998, 37, 3262.

The Klopman-Salem Equation

CoulombicInteractions

OrbitalsInteractions

Filled OrbitalsRepulsion

Why the Observed Regio?

βab(ca+m)(cb+n) + βab(ca)(cb) = βab(ca+m)(cb) + βab(ca)(cb+n)

cacb + can + cbm + mn + cacb = cacb + cbm + cacb+ can

mn > 0

(ca+m)(cb+n) + (ca)(cb) = (ca+m)(cb) + (ca)(cb+n)

ca

ca+mcb+n

cb

ca

ca+m

cb+n

cb

vs

Useful General Values

[3+2] Cycloaddition

AB

C

D E

BA

D E

CB

A

D E

C

Fu, G. C. et al. J. Amer. Chem. Soc. 2003, 125, 10778.

Analoguous to the Diels-Alder Reaction [π4s+π2s]

Cu

EtO2C

NN

R

O

H

[3+2] Cycloaddition

N N Bn

O

Stoltz, B. M. et al. J. Amer. Chem. Soc. 2003, 125, 15000.

[3+2] Cycloaddition, Bond Strength Importance

AB

C

D E

BA

D E

CB

A

D E

C

[3+2] Cycloaddition, Some Useful Values

Ene Reaction : Special Case of Cycloaddition

IntramolecularLevel 1

IntramolecularLevel 2

RO

HHO

S

H

RO

HHO

S

H

RO

S

OH

H

HH

[(π2s+σ2s)+π2s] Usually facilitated by a enophile with a low lying LUMO

enophile

H H

H

H H

H

HHH

Some Application...

O

O

H

H

OO

OH

OHH H O

O

O

O

a b

c

Inomata, K. et al. Org. Lett. 2004, 6, 409.

Recent Use of a Ene/Retro-Ene Process

Corey, E. J. et al. Org. Lett. 2003, 5, 1999.

Halls, D. G. et al. J. Org. Chem. 2004, 69, 8429.

Electrocyclic Rearrangments

Why?

Driving forces can be:

- Geometric tension- Aromatic stabilization (formation of an aromatic moiety)- Delocalization (opening or closing permits delocalization in an other

pi system)

The Same Trick for Opening/Closing

How to know how it closes or open?

The simple trick: Take the open system (polyene) and apply the same principle as seen earlier by simply considering the HOMO of the polyene

4n+2 electrons HOMO (2,6,10,14...) Only Disrotatory opening/closing permitted thermally4n electrons HOMO (4,8,12,16...) Only Conrotatory opening/closing permtted thermally

Disrotatory (4n+2 e-)Conrotatory (4n e-)

Torquoselectivity

If R is electrondonating, then thisfilled orbital would unfavorably interact with thebreaking sigma bond, so outward opening is favored.

If R is electronwithdrawing, then thisempty orbital would favorably interact with the

breaking sigma bond, so inward opening is favored.

R

R

Houk, K. N. et al. J. Am. Chem. Soc. 2003, 125, 5072.

Torquoselectivity : Some Useful Values

Houk, K. N. et al. J. Am. Chem. Soc. 2003, 125, 5072.

Recent Example of a Electrocyclic Rearrangment

Hsung, R. P. et al. J. Org. Chem. 2003, 68, 1729.

[1,j] Shift, Definition and possibility

R R

Suprafacial + retention = SUPRASuprafacial + inversion = ANTARAAntarafacial + retention = ANTARAAntarafacial + inversion = SUPRA

4n+2 electrons processes (2,6,10,14...) Only SUPRA permitted thermally4n electrons process (4,8,12,16...) Only ANTARA permtted thermally

Hydrogen shift: The valence orbital of H being an 1S (spherical) orbital), inversion is impossible with this atom.

An antarafacial migration is only possible with a polyene of at least 6 carbons.

In cyclic systems, antarafacial migrations are impossible in smaller than 10 memberedrings.

[i,j] Shift, Even More Possibility

So... Only 4n+2 (2,6,10,14...) electrons processes (SUPRA) are permitted thermally

Migration of a sigma along two pi systems. Only suprafacial-suprafacial migrations are allowed geometrically

Some nomenclature...

HO HO

OO

XX

Cope Rearrangment

Oxy-Cope Rearrangment

Claisen Rearrangment

Wittig[2,3] Rearrangment

Recent Examples of [i,j] Shifts, Barriault

Oxy-cope

Claisen

Level 2 intramolecularene

Barriault, L. et al. J. Am. Chem. Soc. 2004, 126, 8569.

Dyotropic Rearrangments

Type 1Type 2

Recent example of a type 2 dyotropic shift used in a total synthesis

Houk, K. N. et al. J. Am. Chem. Soc. 2003, 125, 5111.

Simultaneous intramolecular migration of two sigma bonds

Now for Photochemistry

Advantages:

Non thermic activation (low temperature)

Give access to thermally forbidden processes

Photopumping (synthesis of high energy molecules)

Selective activation of chromophores:

R OMe

OO

R OMe

OO *

*

*

hυ

hυ

hυ

λ =300 nm

λ =254 nm

λ =180 nm

Basics Explained

hυ

R

R

R

R

R

R

heat light

Quantum Yield: Φ = # molecules transformed / # photons absorbed

The way to measure it : Using an actinometer

The LUMO of the compound becomes a SOMO, the highest occupied orbital, so thereaction occurs through that orbital: A thermally fobidden process now becomes permitted

Some Numbers (Activation Energy)

First the Practical Stuff... (Absorbance)

Jablonsky Diagram

Ca Cb Ca CbDouble bond Single bond

hυ

π

π*

π

π*

σ σ

Ca CaCb Cb

Photodissociation

Ca Cb Ca Cb

hυ

Single bond Radical pair

σ σ

σ* σ*

Ca CaCb Cb

Photosensibilization

Sens React

S0

S1T1

S1

T1

S0

Esens Ereact

Esens < Ereact

E*3sens > E*3

react

E

Photosensibilization

Ph

O

Ph

O

Ph

O*1 *3

Ph

O *3

Ph

O *3

With acetophenone

With benzophenone

E*3norbonene = 309 kJ

E*3benzophenone = 288 kJ

E*3acetophenone = 309 kJ

hυ

hυ

ISC

ISC

Ph2CO Ph2CO*1 Ph2CO*3

O

Ph Ph

O

PhPh

O

PhPh

1) Spininversion

2) Cyclization

Classical Reactions (Norrish Fragmentation)Norrish Type 1 fragmentation

R R'

O

R R'

O *1

R R'

O *3

R R'

O *3

R R'

O

R'

O

R

- CO2R R'R R'

hυ

Norrish Type 2 fragmentation

hυR

O*3R'

R

OR'H *3

R

OHR'

R

OHR' *3

R

OHR'

R

HO

R'

Photopumping

Wavelength

A A

B

CO2Me

CO2Me

CO2Me

CO2Me

A B

hυ

low temp.