Chemistry 125: Lecture 56 February 25, 2011 Generalized Aromaticity Cycloaddition – Diels-Alder Electrocyclic Stereochemistry Dewar Benzene 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 pp

Generalized Aromaticity pK a 15 vs. 16 for H 2 O H H HH H H e.g. J&F Sec. 13.6pp. 587, 592 cyclo-C 7 H 8 cyclo-C 7 H 7 - pK a 39 (despite more resonance structures) 6  electrons (4n+2) 8  electrons (4n, antiaromatic) R H R R + Ph 3 C + 2  electrons (4n+2) H HH H H OH - unusually stable cation (triply benzylic) + Ph 3 CH R R R + even more stable e.g. J&F Sec p. 591 Same for cyclo-C 7 H 8 + Ph 3 C + cyclo-C 7 H 7 + (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 , 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. folded transition state flattened product H H H H H H cis Z H H H H Z E trans

Cycloadditions: Diels-Alder Regiochemistry 9% yield 45% yield 20°C Perhaps an allylic + / enolate - intermediate stabilized by terminal CH 3 or unsymmetrical Transition State? ? Perhaps Steric Hindrance? Note: Diene is over C=O as well as C=C

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

H H H H Cycloadditions: Diels-Alder Stereochemistry (Diene) CH 2 OH CH 3 5 min 120°C (2E,4E)-2,4-hexadien-1-ol maleic anhydride all cis 81% yield 15 hr 150°C one trans H CH 3 Prefers s-trans conformation, which is not reactive. CH 3 H (2E,4Z)-2,4-hexadiene

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

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

Diels-Alder Reaction cyclic   electron transition state Transition State Motion front viewside 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 h (UVB) 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

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

11 33 conrotationdisrotation Möbius 22 Aromatic Analogue (Hückel Connectivity) Hückel 22 11 33 44 55 66  11 22 33 44  22 11 33 44 55 66 22 11 33 44 55 66  11 22 33 4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 Conrotation is preferred for 4n-electron shift? Disrotation preferred for 6-electron shift CH 3 (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!

CON 4e CON for 4n CON 8e DIS 6e DIS for 4n+2 e.g. J&F Sec pp H3CH3C CH 3 ~0.005% CH % 280°C CH 3 (forms the less stable isomer) (less stable isomer) Bias >11 kcal/mole -10°C CH 3

22  Transition State HOMO 11  disrotation 6e Hückel bottom touches top (odd # of nodes) top touches top (even # of nodes) conrotation 4e 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 t 1/2 = 2 days (room temp) -11 kcal -75 kcal 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 for Structure 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 pp. 533 Vibrational (Infrared) e.g. F&J sec. 15.4, pp NMR (Radio) e.g. F&J sec , pp

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