Synthesis and Properties of Cyclooctatetraene Congeners

2014. 12. 3

Tobe Lab.

Kazuya Fujita

1

Contents

• Introduction Aromaticity- Hückel’s Rule and NICS(0) value

Structure and physical properties of cyclooctatetraene and its congeners

Biradical character

• Twisted cyclooctatetraene congeners Synthesis and physical properties

My work and results

• Summary

2

Hückel’s Rule and NICS(0) Value

• Hückel’s Rule:

3

aromatic (芳香族 )

non-aromatic (非芳香族 )

anti-aromatic (反芳香族 )

number ofp electrons

NICS(0) Value

negative

positive

zero

( N = 0, 1, 2, …)

4N + 2

4N

planar

non-planar

a rule to distinguish whether cyclic conjugated polyenes will have aromatic property on the basis of stabilization energy

p-conjugatedcyclic compounds

• NICS(0) value: a value by theoretical calculations to estimate aromatic property

• larger absolute value means stronger aromaticity/anti-aromaticity

structure

Hückel’s Rule and NICS(0) Value

4

aromatic (芳香族 )

non-aromatic (非芳香族 )

anti-aromatic (反芳香族 )

number ofp electrons NICS(0) Value

negative

positive

zero( N = 0, 1, 2, …)

4N + 2

4N

planar

non-planar

• benzene NICS(0): -11.5

• aromatic compound is stabilized by resonance energy

• planar• has 6 p electrons

aromatic

cyclic conjugatedpolyenes

Calculatied by HF/6-31G*//B3LYP/6-31G*

resonance (共鳴 ):• two forms are not under equilibrate (平衡 ) • the true structure is the mixture of two forms

all bond lengths are equal (1.39 Å)

Cyclooctatetraene (COT)

• has 8 p electrons• alternating single and double bonds• non planar tub-shaped structure

5

non-aromatic

HC

HC

HC CH

CH

CH

CHHC

C

C

C C

C

C

CCH H

H

H

HH

H

H

= =

1.34 Å 1.48 Å

126.1 °

NICS(0): +1.9

• tub-to-tub inversion in solution

flexible p conjugated skeleton

equilibrate (平衡 ),

not resonance (共鳴 )

COT Congeners and NICS(0) Value

6

anti-aromaticNishinaga, T. et al. J. Am. Chem. Soc. 2010, 132, 1066.

NICS(0): +17.4

S

S

S

S

S

S

1

S

S

S

S

S

S

Crystal structure of 1

NICS(0): +1.9• has 8 p electrons• non-planar non-aromatic

• Planarized COT by introducing substituents

Biradical Character

• Ethylene

7

• o-Quinodimethane

cleavage of p bond (double bond) leads to loss of bonding energy

open shell structure is stabilized by forming benzene ring

closed shell open shell

C C

H

HH

H

C C

H

HH

H

CH2

CH2

CH2

CH2

closed shell open shell

resonance　 (共鳴 )

H3C

H3C

H3C

H3C

H3C

H3C

H3C

H3C

CH3

CH3

400 °C

N2, 1 atm

[4+4] dimerization

63%closed shell open shell

• Formal [4+4] dimerization of o-quinodimethane

Boekelheide, V. et al. J. Am. Chem. Soc. 1981, 103, 1777.

open shell structure contributes to resonance hybride and has diradical character

Dimerization of Indeno[2,1-a]fluorenes

• dimerization and formation of COT ring undergo one step• more p conjugated system having COT ring can be synthesized

8new synthetic method of COT congeners

H

Br

5

Br

H

[4+4]dimerization

HBr

H

Br

BrH

HBr

t-BuOK

THF34%

2

3 4

t-BuOK -HBr t-BuOK -2HBr

Crystal Structure and NICS(0) Value of Dimer 5

9

An ORTEP drawing of Dimer 5.Single crystals of 5 suitable for X-ray analysis were obtained from benzene/methanol.

C1C2

C3

C4

C1’

C1-C1’-C4’-C4 C2-C3-C3’-C2’

29.2 °38.6 °

torsion angle

C2’C3’

C4’

COT ring is twisted

NICS(0): +11.9

decreased

anti-aromaticity

Calculatied by HF/6-31G*//B3LYP/6-31G*

steric repulsion

My Work

10Tobe, Y. et al. Angew. Chem. Int. Ed. 2013, 52, 4184.

Li

Bu

1) n-BuLi, THF -78 °C then r.t.2) H2O

Bu

Bu

[4+4]addition

Bu

Bu

23%

dehydrogenation

Bu =

R

R HBr

BrH

R

R

R

R1) [4+4] dimerization

Dimer 6 (R = CH3)Dimer 7 (R = Ph)

R

R Br

H

base

-HBr 2) -2HBrPh =

H3C

H3C HBr

BrH

H3C

H3C

CH3

CH3

Dimer 8

base

-HBr H3C

H3C Br

H

1) [4+4] dimerization

2) -2HBr

dehydrogenation

H3C

H3C

CH3

CH3

Dimer 8'

Structures of Dimer 7 and 8’

11

Optimized structure by DFT(B3LYP/6-31G* )

HOMO LUMOHOMO-

LUMO gaptorsion angle

redtorsion angle

orangeNICS(0)

7 -4.89 eV -2.81 eV 2.08 eV 42.7 ° 33.6 ° +12.7

8’ -5.10 eV -2.30 eV 2.80 eV 4.5 ° 5.5 ° +12.2

Ph

Ph

Ph

Ph

Dimer 7

H3C

H3C

CH3

CH3

Dimer 8'

Synthesis of dibromodihydroindenofluorene 12

12

Mataka, S. et al. New. J. Chem. 2003, 27, 1377.

PhPh

PhPhO

Ph

PhO

OCH3

O

OCH3

10

polyphosphoric acidP2O5

neat56%

CHCl394%

H3COOC COOCH3

9

Ph

Ph HBr

BrH

12one isomer

Ph

Ph HOH

OHH

two isomers (1 : 0.63)

from crude 1H NMR

PBr3

CH2Cl269% (2 steps)

Ph

Ph O

O

11

NaBH4

THF

Attempted Synthesis of Dimer 7

13

Ph

Ph Br

H Ph

Ph

O

O

Br

HPh

Ph

O

OO2

-HBr[4+2] addition

Ph

Ph

Ph

Ph

7

Ph

Ph O

OTHF14%

t-BuOK

Ph

Ph HBr

BrH

12 11

THF

t-BuOK

t-BuOK

Reaction Mechanism of Dimerization

14

Br

Br

H

H

3 TS1

Br

BrH

H BrH

HBr

TS2INT1 INT2

-2HBr

Br

H5

BrH

BrH

Calculated at RB3LYP/6-31G(d) + LanL2DZ (for Br) (TS1, INT2)Calculated at UB3LYP/6-31G(d) + LanL2DZ (for Br) (INT1, TS2)

by Dr. Nobusue, S

BrH

BrH

HH

H

H

BrH

BrH

HH

H

H

Reaction Mechanism of Dimerization

15Calculated at RB3LYP/6-31G(d) + LanL2DZ (for Br)

Structure of TS1

Br

Br

H

H

3 TS1

Br

BrH

H BrH

HBr

TS2INT1 INT2

-2HBr

Br

H5

BrH

BrH

-40

-30

-20

-10

0

10

20

30

Energy Diagram of Dimerization

16

5

Br

Br

H

H

BrH

HBr

INT2

INT1TS1

TS2

3

Rel

ativ

e en

ergy

/ k

cal m

ol-1

Br

H

Calculated at RB3LYP/6-31G(d) + LanL2DZ (for Br) (TS1, INT2); Calculated at UB3LYP/6-31G(d) + LanL2DZ (for Br) (INT1, TS2) by Dr. Nobusue, S

reaction coordinate

= Ph

TS1

Br

Br

H

H

BrH

BrH

-40

-30

-20

-10

0

10

20

30

Energy Diagram of Dimerization

17

5

Br

Br

H

H

BrH

HBr

INT2

INT1TS1

TS2

3

Rel

ativ

e en

ergy

/ k

cal m

ol-1

Br

H

Calculated at RB3LYP/6-31G(d) + LanL2DZ (for Br) (TS1, INT2); Calculated at UB3LYP/6-31G(d) + LanL2DZ (for Br) (INT1, TS2) by Dr. Nobusue, S

reaction coordinate

= Ph

TS1

higher activation barrier

Br

Br

H

H

Synthetic Scheme of Dimer 8 and 8’

18

HBr

BrH

8

HOH

OHH

basePBr3

CH2Cl2

8'

dehydrogenation

18

NH2

Br

NH2

Br

Br1) NaNO2, 48%aq.HBr2) CuBr, 48%aq.HBr

COOCH3

COOCH3

14, Pd(PPh3)4Aliquat 366 O

O

NaBH4

THFCH2Cl283%

Friedel-Craftsreaction

toluene, EtOHK2CO3 aq.

48%

NBS

52%

17

15 16‡

†　 Steven, G. N. et al. PCT Int. Appl. US 03/022898, A1, 2003. ‡　 Lai, Y-H. et al. J. Chem. Soc. Perkin Trans. 2 1993, 7, 1377.

COOH COOH

I

Pd(OAc)2, iodobenzene diacetateI2, tetrabutylammonium iodide

methanolH2SO4 COOCH3

I1,2-dichloroethane

Pd(dppf)Cl2HBpin

NEt3, dioxane

COOCH3

B

14†

22% (3 steps)

O

O13

Summary

• Non-planar tub-shaped COT exhibits non-aromaticity and planarized COT exhibits anti-aromaticity.• Twisted COT congener was formed by dimerization of indeno[2,1-a]fluorenes and its twisted COT ring exhibits decreased anti-aromaticity.• Synthesis of Ph-substituted indenofluorene dimer was attempted, but unexpected reaction occurred.

19

BrH

HBr

H

Br

Br

H

[4+4]additiont-BuOK

THF-HBr

HBr

t-BuOK

THF-2HBr

34%

Ph

Ph

Ph

Ph

Ph

Ph O

OTHF14%

t-BuOK

Ph

Ph HBr

BrHTHF

t-BuOK