Origin of the p Facial Stereoselectivity

of Bicyclic and Tricyclic Olefins

1

Geometrical Dependence of the Highest Occupied Molecular Orbital

in Bicyclic Systems:

Motonori Tsuji Institute of Molecular Function

©Institute of Molecular Function Motonori Tsuji

M

L

S

Nu:

Cram’s Rule

OR

Less hindered side

S: small substituent M: medium substituent L: large substituent

Nu: S

L MNu

R OH

S

L MOH

R Nu

Major Product

eclipsed

2 ©Institute of Molecular Function Motonori Tsuji

M S

L

M

L

S

O R

S

L

M

O R

M

L

S

O R

O R

Nu:

Felkin-Anh Model

s* s* p* p*

Nu: Nu:

Hyperconjugation

antiperiplanar ‡

Nu:

Nu:

s*

p*

LUMO

HOMO

Ener

gy

S: small substituent M: medium substituent L: large substituent

M

L

S

O R

M

L

S

O R

M

L

S

O R

3 ©Institute of Molecular Function Motonori Tsuji

R

O-

H

Cieplak Model

s*‡

s

R

O-

H

s

s*‡

R

H

OH

Nu

R

H

Nu

OH

Axial Attack

Equatorial Attack

‡

‡

Major Product antiperiplanar

4 ©Institute of Molecular Function Motonori Tsuji

5

X

W

W W

W

X

W

X

D

D D

D

X

D

Sterically Unbiased Systems for Facial Selectivity

X = O, CH2

W: Electron-withdrawing Group

D: Electron-donating Group

Electrophiles for Olefins Nucleophiles for Carbonyls

X

W

X

D

X

W

©Institute of Molecular Function Motonori Tsuji

6

X

W

W

X

D

D

X = O, CH2 W: Electron-withdrawing Group

D: Electron-donating Group

Explanation Using Cieplak Model

Steric, electrostatic, and torsional effects can ignore in these sterically unbiased systems.

©Institute of Molecular Function Motonori Tsuji

Electrophiles for Olefins Nucleophiles for Carbonyls

A Reverse Facial Stereoselectivity with the Electron-donating Cyclopropane Ring

7

Cram’s Rule, Felkin-Anh Model, Cieplak Model Steric Effect, Electrostatic Effect, Torsional Effect,

Ruled Out

anti

©Institute of Molecular Function Motonori Tsuji

Model Systems in Which the p Nature of Cyclopropane Is Maximized

Strong Electrophiles

Weak Elecrophiles

Weak Elecrophiles

8

Strong Electrophiles No Selectivity

Both Electrophiles

anti

anti

anti

anti syn

©Institute of Molecular Function Motonori Tsuji

Geometrical Dependence of the HOMO in the Non-Conjugated Dienes

9

A1-symmetry orbitals (circles) and B1-symmetry orbitals (squares) were obtained at the RPM3 (solid), RB3LYP/6-31G* (open), and ROVGF/6-31G*//HF/6-31G* (dotted line) methods.

©Institute of Molecular Function Motonori Tsuji

Though-space (Hyperconjugation) Though-bond Though-space

(Hyperconjugation) Though-bond

Origin of the Facial Stereoselectivity in the Four-center Geometry

H

H

H

HHOMO

p

s

sp2 – sp2

Though-space

Hyperconjugation

Larger p lobes

Hyperconjugation p

NHOMO

p

p

s

Though-bond

Though-bond

HOMO

NHOMO

Though-space

Larger p lobes

inverse

sp2 – sp2 sp2 – sp2

10

θ2

θ1

H

H

H

H

θ2 θ1 < 120º <

sp2 – sp2 s s

©Institute of Molecular Function Motonori Tsuji

Origin of the Facial Stereoselectivity in the Three-center Geometry

HOMO

p

s

sp2 – sp2

Though-space

Hyperconjugation

Larger p lobes p

NHOMO

p*

Homoconjugations (Homoaromaticity)

Larger p lobes

Strong Electrophiles

Weak Electrophiles inverse inverse

Since strong electrophiles have an activated LUMO, the olefinic molecules can not homoconjugate intramolecularly.

Weak Electrophile

LUMO

LUMO

Strong Electrophile

11

θ3 120º <

θ3

©Institute of Molecular Function Motonori Tsuji

Though-bond

W: Electron-withdrawing Group

HOMO

p

s

s sp2 – sp2

Though-bond

Hyperconjugation

HOMO

p

s

s sp2 – sp2

Though-bond

Hyperconjugation

Larger p lobes Larger p lobes

Effect of the Electron-withdrawing Group on the Facial Stereoselectivity

W

W

W

W

W

W

W

W

W

W W

W

H

H

12

W

W

W

W

W

W

W

W

©Institute of Molecular Function Motonori Tsuji

D

D

D

D

D

D

D

D

D

D

D

D

H

H

HOMO

p

s

s

sp2 – sp2

Though-bond

Hyperconjugation

HOMO

p

s

s

sp2 – sp2

Though-bond

Hyperconjugation

Larger p lobes

Larger p lobes

Effect of the Electron-donating Group on the Facial Stereoselectivity

D: Electron-donating Group

13

D

D

D

D

D

D

D

D

©Institute of Molecular Function Motonori Tsuji

Conclusions

HOMO of molecule depends on the geometry. This HOMO determines the facial stereoselectivity. Depending on the molecular geometry, the symmetrical p orbital is mixed with the different types of s orbitals. These s orbitals are mixed with p orbital via through-bond interactions. As a result, through-bond interactions, such as hyperconjugation, bring about the orbital rehybridization (pyramidalization) and tilting, leading to the desired transition structure. The magnitude of through-space interaction affects on the orbital sequence, thus leading to the reverse selectivity. In the three center geometry, homoconjugation (homoaromaticity) strongly affects on the orbital sequence, thus giving the ambident selectivity.

14 ©Institute of Molecular Function Motonori Tsuji