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

Generalization of Aromaticity: 4n+2 Stability Transition State “Aromaticity” Cycloadditions & Electrocyclic Reactions e.g. J&F Sec. 13.6 pp. 582-595

Generalized Aromaticity H H OH- pKa 15 vs. 16 for H2O 6  electrons (4n+2) cyclo-C7H8 cyclo-C7H7- pKa 39 (despite more resonance structures) 8  electrons (4n, antiaromatic) e.g. J&F Sec. 13.6 p. 591 R H + Ph3C+ + Ph3CH R + even more stable unusually stable cation (triply benzylic) 2  electrons (4n+2) Same for cyclo-C7H8 cyclo-C7H7+ (cycloheptatrienyl “tropylium”) e.g. J&F Sec. 13.6pp. 587, 592 6  electrons (4n+2)

Pericyclic Reactions (in which transition states are “aromatic”) Cycloadditions: Diels-Alder (e.g. J&F Sec. 12.12, 14.3) Electrocyclic Reactions

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

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?

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 150-160°C 68% yield cis alkene cis cyclohexene 150-160°C 84% yield trans alkene trans cyclohexene e.g. J&F Sec. 12.12, p. 549

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

Diels-Alder Variety propenal (“acrolein”) 150°C 20°C k ~1 M-1s-1 160°C e.g. J&F Sec. 14.3, pp. 628-630

    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

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

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

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.

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

   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

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

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)

4-electron cycloaddition!

(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. 27.2 pp. 1343-1346

  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

Opening Dewar Benzene (1866)

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!

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

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

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 for Structure and Dynamics Electronic (Visible/UV, sec. 12.7-12.8 pp. 533) Vibrational (Infrared, sec. 15.4, pp. 707-713) NMR (Radio, sec. 15.5-15.9, pp. 713-749) 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)

“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.

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

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).

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”

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”

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).

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.

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)

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

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

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”

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)

End of Lecture 56 February 25, 2011 Copyright © J. M. McBride 2011. Some rights reserved. Except for cited third-party materials, and those used by visiting speakers, all content is licensed under a Creative Commons License (Attribution-NonCommercial-ShareAlike 3.0). Use of this content constitutes your acceptance of the noted license and the terms and conditions of use. Materials from Wikimedia Commons are denoted by the symbol . Third party materials may be subject to additional intellectual property notices, information, or restrictions.   The following attribution may be used when reusing material that is not identified as third-party content: J. M. McBride, Chem 125. License: Creative Commons BY-NC-SA 3.0