1. Generalized Aromaticity Cycloaddition – Diels-Alder
Chemistry 125: Lecture 56 February 25, 2011
Generalized Aromaticity
Cycloaddition – Diels-Alder
Electrocyclic Stereochemistry Spectroscopy Introduction Electronic Spectroscopy
Preliminary
This
For copyright notice see final page of this file

2. Generalization of Aromaticity: 4n+2 Stability Transition State “Aromaticity” Cycloadditions & Electrocyclic Reactions
e.g. J&F Sec pp

3. Generalized AromaticityH H
OH-
pKa 15
vs. 16 for H2O
6  electrons (4n+2)
cyclo-C7H cyclo-C7H7- pKa 39 (despite more resonance structures)
8  electrons (4n, antiaromatic)
e.g. J&F Sec p. 591 R H
+ Ph3C+
+ Ph3CH R +
even more stable
unusually stable cation (triply benzylic)
2  electrons (4n+2)
Same for cyclo-C7H cyclo-C7H7+
(cycloheptatrienyl “tropylium”)
e.g. J&F Sec. 13.6pp. 587, 592
6  electrons (4n+2)

4. Pericyclic Reactions (in which transition states are “aromatic”)
Cycloadditions: Diels-Alder
(e.g. J&F Sec , 14.3)
Electrocyclic Reactions

5. Cycloadditions: Diels-Alder
diene
ene
Ring
4 + 2 electrons
4 + 2 electrons
How does p become s? H
LUMO
HOMO Z H H H
trans
cis E H H Z H
Approach parallel to p-orbital axes.
folded
transition
state
flattened product

6. Cycloadditions: Diels-Alder Regiochemistry
Perhaps Steric
Hindrance?
Note: Diene is over C=O as well as C=C
9% yield
45% yield
20°C
Perhaps an enolate- allylic+ intermediate ?
stabilized by terminal CH3
or unsymmetrical Transition State?

7. Cycloadditions: Diels-Alder
Stereochemistry (Ene)
Diene just “sits down” on Ene
forming two s-bonds simultaneously from the same face.
No rotatable intermediate with only one new s bond °C
68% yield
cis alkene
cis cyclohexene °C
84% yield
trans alkene
trans cyclohexene
e.g. J&F Sec , p. 549

8. Cycloadditions: Diels-Alder
Stereochemistry (Diene)
maleic anhydride
CH2OH
CH3 H
5 min
120°C
81% yield
all cis
(2E,4E)-2,4-hexadien-1-ol H
CH3 H
Prefers
s-trans conformation, which is not reactive.
15 hr
150°C
CH3 H
one trans
(2E,4Z)-2,4-hexadiene

9. Diels-Alder Variety propenal (“acrolein”) 150°C 20°C k ~1 M-1s-1 160°C
e.g. J&F Sec. 14.3, pp

10.     Transition State Motion HOMO LUMO Transition State HOMO-1
p. 1351
Transition
State
Motion 
HOMO 
LUMO
Transition
State
HOMO-1
Transition
State
HOMO 
HOMO 
LUMO
front view
side view
Diels-Alder Reaction
cyclic electron
transition state

11. Transition
State
Motion
front view
side view
Diels-Alder Reaction
cyclic electron
transition state

12. ? h HOMO () orthogonal to LUMO (*) Shift electron from HOMO to LUMO
p. 1046 ?
HOMO () orthogonal to LUMO (*) h
Shift electron from HOMO to LUMO

13. T-T
A-T-T-G
DNA Double Helix
T-A-A-C
hn (UVB)
T-T
Thymine photodimerization causes a chain kink that inhibits DNA replication & transcription and is believed to be the main source of mutation / melanomas.

14. Pericyclic Reactions (in which transition states are “aromatic”)
Cycloadditions: Diels-Alder
Electrocyclic Reactions

15.    node Möbius requires twist in 1 of 2 ways Preserves Axis
David Benbennick
Möbius
  
requires twist
in 1 of 2 ways
Preserves Axis
Transition State
Motion
Preserves Mirror
top
touches
bottom
(odd # of nodes)
top
touches
(even #
of nodes)
Hückel
conrotation
disrotation

16. 2 1 3 4 5 6  
Möbius 2 1 3 4 5 6  
Hückel
Aromatic Analogue (Hückel Connectivity) 2 1 3 4 5 6 1 2 3
Track the MOs of hexatriene as they transform into those
of cyclohexadiene: !
Preserves Axis
Preserves Axis
Preserves Mirror
Transition State
Motion
Möbius
Hückel
conrotation
disrotation

17. How to study whether Conrotation is preferred for 4n-electron shift?
The transition state favored in going from A to B, must also be favored in going from B to A. (“Microscopic Reversibility”) DH
+11 kcal/mole
CH3
CH3 • •
(less stable isomer) DH
-16 kcal/mole
CH3
(forms the less stable isomer)
Disrotation preferred for 6-electron shift
(4n+2)

18. 4-electron cycloaddition!

19. (forms the less stable isomer)
CON 4e
CH3
99.9%
280°C
H3C
CH3
~0.005%
Bias >11 kcal/mole
DIS 6e
CH3
(forms the less stable isomer)
DIS for 4n+2
CON for 4n
-10°C
CH3
CON 8e
e.g. J&F Sec pp

20.   4e Möbius conrotation 2 Transition State HOMO -1 1 6e Hückel
bottom touches top
(odd # of nodes)
top touches top
(even # of nodes) -1 1 
6e Hückel
disrotation

21. Opening Dewar Benzene
(1866)

22. Calculated Isomers of Benzene (2004)
6 > 100 kcal above benzene have been prepared.
(single bond breaking gives even less stable species)
Calculated Isomers of Benzene (2004)
84 calculated to be < 100 kcal above benzene.
Dewar Benzene (1963) is 74 kcal above benzene but lasts 2 days at room temperature!

23. 4-electron disrotation!
van Tamelen & Pappas (1963)

24. t1/2 = 2 days (room temp) * LUMO  HOMO  HOMO * LUMO
CCC angles require disrotatory
motion
66 kcal/mole more exothermic,
but only 8 kcal/mole “faster”?
t1/2 = 2 days (room temp) 25 33
more strain
* LUMO
 HOMO
 HOMO
* LUMO
-11 kcal
-75 kcal
conrotatory
aromatic
good for 4n electrons

25. But shouldn’t “aromatic” 6--electron transition state be good for disrotation?
It is more fundamental that  LUMO doesn’t overlap  HOMOs (& vice versa).

26. Spectroscopy for Structure and Dynamics
Electronic (Visible/UV, sec pp. 533)
Vibrational (Infrared, sec. 15.4, pp )
NMR (Radio, sec , pp )
O.E.D.
“Specters or straunge Sights, Visions and Apparitions” (1605)
“Sunbeams..passing through a Glass Prism to the opposite Wall, exhibited there a Spectrum of divers colours” Newton (1674)

27. “Atom in a Box” can be used to show:
(1) Spectral transitions for H atom (levels, energy, wavelength)
(2) Static shift of e-density from mixing 2s with 2p (same energy)
(3) Oscillation of e-density from mixing orbitals with different energy because of change in relative phase* with time (add, then subtract).
(a) Oscillating “dipole” from mixing 1s with 2p.
(makes or interacts with light)
“Breathing” from mixing 1s with 2s.
(no interaction with light)
* This is a feature of time-dependent quantum mechanics, where the (complex) phase of a wavefunction changes at a rate proportional to its energy. When energies of the components differ, their relative phases vary in time.

28. superposition e-density+ +
time-dependent
(1s + 2p)2
superposition e-density
Oscillation frequency given by the energy difference between 1s and 2p +

29. Time-Dependance Footnote
A time-dependent wavefunction looks just like the spatial s we have been talking about, except that it is multiplied by eit, where i = (-1), is the energy (expressed in frequency units) of the spatial wavefunction and t is time.
In many cases this makes no difference, because when you “square” the wave function you get eit  e-it = 2. *
BUT when a problem involves actually mixing two states of different energy, one considers a wavefunction of the form eit + eit . If 1 and 2 are different, this means that the two spatial functions cycle in- and out-of-phase with one another. If at a certain time they add, at a time 1/(1-2) later they will subtract. e.g. (1s+2pz) will become (1s-2pz).
This is the source of the oscillation we observe when superimposing functions of different n using Atom-in-a-Box.
* This is different from the mixing involved in forming hybrids or LCAO-MOs, where we just try to guess the best shape for an orbital of one particular energy
for a molecule by analogy with known solutions for a simpler situation (atoms).

30. superposition e-density+ +
time-dependent
(1s + 2p)2
superposition e-density
Oscillating dipole has
“oscillator strength”
interacts with /
generates / absorbs
light
Oscillation frequency given by the energy difference between 1s and 2p +
1s - 2p transition
is “allowed”

31. superposition e-density+ +
time-dependent
(1s + 2s)2
superposition e-density
Symmetrical “breathing”
e-density deformation has
no “oscillator strength”
does not interact
with light’s E-field.
Pulsing frequency given by the energy difference between 1s and 2s +
1s - 2s transition
is “forbidden”

32. n-* Transitions of Organic “Chromophores”:
n+* + - :
n-*
Oscillating electric field wags electrons up and down by mixing n with *. C X :
The large energy gap between n and * makes this transition occur at high frequency (in the ultraviolet).

33. n-* Transitions of Organic “Chromophores”
* mix approaches energy of 2p orbital + - + - + - :
n-*
Oscillating electric field wags electrons up and down by mixing n with *. C X :
With sufficient “conjugation” the * LUMO energy shifts close enough to n that the transition is at visible wavelength. R
e.g. the retinaldehyde imine of rhodopsin, which is the visual pigment in our eyes.

34. Helvetica Chimica Acta, 35, 447 (1952)
-Carotenyne
-Carotene H2
Pd/Pb C H R
During work on the synthesis of Vitamin-A
a Palladium-Lead catalyst was developed, with which one can hydrogenate a triple bond without attacking double bonds already present in the starting material or those created by the hydrogenation.
OPP
OPP
OPP hn D C H R
PPO
Helvetica Chimica Acta, 35, 447 (1952)

35. Autumn Scarlet(?) Tanager Summer Scarlet(!) Tanager Early Fall
©Birdwatchers Digest
Summer Scarlet(!) Tanager
Early Fall
with kind permission of Lloyd Spitalnik
-carotene O:
conjugated O:
isolated
retinal O
canthaxanthin
isozeaxanthin

36. Graph of a Spectrum (IR of Paxil)
Light
Intensity
(2) Light-
Induced
Overlap
(3) Light’s
“Handle”
(changing dipole)
Meaning
of Axes :
(1) Experiment
(1) Color (wavelength)
(2) Quantum Mechanics
(2) Molecular Energy Gap
(3) Classical Mechanics
(3) Molecular Vibration Frequency

37. and to understand Bonding and whether Atoms are linked by “Springs”
Infrared Spectroscopy Using Light to Fingerprint molecules and identify Functional Groups
and to understand Bonding and whether Atoms are linked by “Springs”

38. independent of amplitude 2h
What Makes Vibration Sinusoidal?
(half) amplitude
acceleration
displacement
frequency
velocity
-fx
Newton
Hooke F = - fx
FrequencyConstant!
independent of amplitude 2h
(Text Fig12.6)

39. End of Lecture 56 February 25, 2011
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