Chemistry 125: Lecture 56February 25, 2011

Generalized AromaticityCycloaddition – Diels-Alder

Electrocyclic StereochemistryDewar Benzene

This

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Generalization of Aromaticity:

4n+2 Stability

Transition State “Aromaticity”Cycloadditions &

Electrocyclic Reactionse.g. J&F Sec. 13.6 pp. 582-595

Generalized Aromaticity

pKa 15vs. 16 for H2O

H H

HH

H H

e.g. J&F Sec. 13.6pp. 587, 592

cyclo-C7H8 cyclo-C7H7- pKa 39 (despite more resonance structures)

6 electrons (4n+2)

8 electrons (4n, antiaromatic)

R H

R R

+ Ph3C+

2 electrons (4n+2)

H

HH

H H

OH-

unusually stable cation (triply benzylic)

+ Ph3CH

R

R R

+

even more stable

e.g. J&F Sec. 13.6 p. 591

Same for cyclo-C7H8 + Ph3C+ cyclo-C7H7

+

(cycloheptatrienyl or “tropylium”) 6 electrons (4n+2)

Electrocyclic Reactions

Pericyclic Reactions(in which transition states are “aromatic”)

Cycloadditions: Diels-Alder (e.g. J&F Sec. 12.12, 14.3)

H

H

Cycloadditions: Diels-Alder

4 + 2 electrons

Ring

4 + 2 electrons

enediene

LUMO

HOMO

How does become ?

Approach parallel to p-orbital axes.

foldedtransition

state

flattened product

H

H

H

H

H

H

cis

Z

H

H

H

H

Z

E tran

s

Cycloadditions: Diels-AlderRegiochemistry

H

H

CO2CH3

H

H

H

H

H

CH3

H

H

CO2CH3

H

CO2CH3H3C

CO2CH3

H3C

H

H

H

HCH3

9% yield

45% yield

20°C Perhaps an

allylic+ / enolate- intermediate

stabilized by terminal CH3

or unsymmetrical Transition State?

?

Perhaps StericHindrance?Note: Diene is

over C=O as well as C=C

CH3O2C

H

H

CO2CH3

trans alkene trans cyclohexene

cis alkene cis cyclohexene

H

H

CO2CH3

CO2CH3

Cycloadditions: Diels-Alder

Stereochemistry (Ene)Diene just “sits down” on Ene

68% yield

84% yield

e.g. J&F Sec. 12.12, p. 549

150-160°C

150-160°C

forming two -bonds simultaneously from the same face.

CO2CH3

CO2CH3

H

H

No rotatable intermediate with only one new bond

H

CO2CH3

H

CO2CH3

O

O

O

H

H

O

O

O

H

H

Cycloadditions: Diels-AlderStereochemistry (Diene)

H

H

H

H

O

O

O

CH2OH

CH3

5 min

120°C

(2E,4E)-2,4-hexadien-1-ol

maleic anhydride

all cis81% yield

15 hr

150°Cone trans

H

H

H

H

O

O

O

H

CH3

CH3Prefers s-trans

conformation, which is not

reactive.

CH3

CH2OH

H

H

CH3

H

H3C

H

CH3

H

(2E,4Z)-2,4-hexadiene

CNNC

Diels-Alder Variety

O H

propenal (“acrolein”)

OO

H

H

OHO

He.g. J&F Sec. 14.3, pp. 628-630

CN

CNCNNC

C

C

CO2CH3

CO2CH3

CH3 CH3

CO2CH3

CO2CH3

160°C

150°C

20°C

k ~1 M-1s-1

LUMO

HOMO

Diels-Alder Reactioncyclic electrontransition state

HOMO

LUMO

TransitionState

Motion

front view side view

TransitionState

HOMO-1

TransitionState

HOMO

p. 1351

Diels-Alder Reaction

cyclicelectrontransition state

TransitionState

Motion

front view side view

?

HOMO () orthogonal to LUMO (*)

h

Shift electron from HOMO to LUMO

e.g. J&F p. 1046

A-T-T-G

DNA Double Helix

T-A-A-C

T-T

T-T

h (UVB)

Thymine photodimerization causes a chain kink that inhibits DNA replication & transcription and is believed to be the main source of mutation / melanomas.

N

N N

N

O

O

O

O

chainchain

CH3CH3

H H

HH

Pericyclic Reactions(in which transition states are “aromatic”)

Cycloadditions: Diels-Alder

Electrocyclic Reactions

conrotation disrotation

requires twistin 1 of 2 ways

Hückel

Transition StateMotion

top

touches

top(even #

of nodes)

top touches

bottom

(odd # of nodes)

Dav

id B

enb

en

nick Möbius

Preserves Mirror

Preserves Axis

node

13

conrotation disrotationMöbius

2

Aromatic Analogue (Hückel Connectivity)

Hückel

2

1

3

4

5

6

1

2

3

4

Hückel

21

3

4

5

6

2

1

3

4

5

6

1

2

3

4

Möbius

!

Track the MOs of hexatriene as they transform into those

of cyclohexadiene:

Preserves Mirror

Preserves Axis

H

-16 kcal/mole

H

+11 kcal/mole

How to study whether Conrotationis preferred for 4n-electron shift?

Disrotation preferred for 6-electron shift

CH3 CH3 CH3 CH3

CH3

CH3

CH3 CH3

(forms the less stable isomer)

(less stable isomer)• •• •

(4n+2)

The transition state favored in going from A to B, must also be favored in going from B to A. (“Microscopic Reversibility”)

4-electron cycloaddition!

CON4e

CON for 4nCON

8e

DIS6e DIS for 4n+2

e.g. J&F Sec. 27.2 pp. 1343-1346

H3C CH3

~0.005%CH3 CH3

CH3

CH3

99.9%

280°C

CH3 CH3 CH3 CH3

(forms the less stable isomer)

(less stable isomer)

Bias >11 kcal/mole

-10°C

CH3

CH3CH3 CH3

2

Transition State HOMO-1

1

disrotation6e Hückel

bottom touches top(odd # of nodes)

top touches top(even # of nodes)

conrotation4e Möbius

If you could run it forwards!

Opening Dewar Benzene

(1866)

Strained

Stable

Really wants to open up

Calculated Isomers of Benzene

(2004)

84 are calculated to be < 100 kcal above benzene.

6 > 100 kcal above benzene have been prepared.(single bond breaking gives even less stable species)

Dewar Benzene (1963) is 74 kcal above benzene but lasts 2 days at room temperature!

van Tamelen & Pappas (1963)

4-electron disrotation!

CCC angles require disrotatory

motion

HOMO* LUMO

t1/2 = 2 days (room temp)

-11 kcal

-75 kcal

25

33

conrotatory

more strain

aromatic

HOMO

66 kcal/mole more exothermic,but only 8 kcal/mole “faster”?

good for 4n electrons

* LUMO

But shouldn’t “aromatic” 6--electron transition state be good for disrotation?

It is more fundamental that LUMO doesn’t overlap HOMOs (& vice versa).

Spectroscopy forStructure and Dynamics

“Sunbeams..passing through a Glass Prism to the opposite Wall, exhibited there a Spectrum of divers colours”

Newton (1674)

“Specters or straunge Sights, Visions and Apparitions” (1605)

O.E.D.

Electronic (Visible/UV) e.g. F&J sec. 12.7-12.8 pp. 533

Vibrational (Infrared) e.g. F&J sec. 15.4, pp. 707-713

NMR (Radio) e.g. F&J sec. 15.5-15.9, pp. 713-749

End of Lecture 56February 25, 2011

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