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. 13.6 pp. 582-595 Generalized Aromaticity H H H H H OH- H H pKa 15 H H cyclo-C7H8 R H H 6 electrons (4n+2) cyclo-C7H7- pKa 39 (despite more resonance structures) e.g. J&F Sec. 13.6 p. 591 8 electrons (4n, antiaromatic) R H + R vs. 16 for H2O R Ph3C+ unusually stable cation (triply benzylic) Same for cyclo-C7H8 + Ph3C+ (cycloheptatrienyl or “tropylium”) + + R Ph3CH R even more stable 2 electrons (4n+2) cyclo-C7H7+ 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 become ? H H HH HH E H trans Z HOMO H H Z LUMO Approach parallel to p-orbital axes. H folded transition state flattened product H cis H Cycloadditions: Diels-Alder Regiochemistry Note: DieneHis over C=O H as well as C=C Perhaps Steric Hindrance? CH3 H H H H CO2CHH33C 9% yield H Perhaps an allylic+ / enolateintermediate 20°C H H H CO2CH3 CO2CH3 CO2CH3 ? H CH3 H H H H3C 45% yield stabilized by terminal CH3 or unsymmetrical Transition State? Cycloadditions: Diels-Alder Stereochemistry (Ene) Diene just “sits down” on Ene forming two -bonds simultaneously from the same face. No rotatable intermediate with only one new bond H CO2CH 3 150-160°C CO2CH3 H 68% yield H H CO2CH3 CO2CH3 cis alkene CH3O2C cis cyclohexene H H 150-160°C CO2CH3 H H CO2CH3 trans alkene 84% yield CO2CH3 trans cyclohexene e.g. J&F Sec. 12.12, p. 549 Cycloadditions: Diels-Alder Stereochemistry (Diene) maleic anhydride CH2OH H CH2OH O H H O H H O H 5 min O 120°C O CH3 (2E,4E)-2,4-hexadien-1-ol H O Prefers H s-trans H3C 15 hr conformation, O 150°C which is not H H H reactive. CHO3 CH3 (2E,4Z)-2,4-hexadiene H 81% yield H O CH3 H CH H 3 H all cis O O H CH3 one trans H O Diels-Alder Variety CH3 CH3 CO2CH3 C CO2CH3 150°C C CO2CH3 CO2CH3 20°C k ~1 M-1s-1 NC CN NC CN CN CN 160°C O O O H H O O H H propenal (“acrolein”) O H H e.g. J&F Sec. 14.3, pp. 628-630 p. 1351 Transition State Motion HOMO LUMO Transition State HOMO-1 HOMO HOMO LUMO front view Diels-Alder Reaction cyclic electron transition state side view Transition State Motion front view Diels-Alder Reaction cyclic electron transition state side view ? HOMO () orthogonal to LUMO (*) h Shift electron from HOMO to LUMO e.g. J&F p. 1046 chain chain H DNA Double Helix N O H N N O N H H O CH3CH3 O h (UVB) T-T T-T Thymine photodimerization causes a chain kink that inhibits DNA replication & transcription and is A-T-T-G believed to T-A-A-C be the main source of mutation / melanomas. Pericyclic Reactions (in which transition states are “aromatic”) Cycloadditions: Diels-Alder Electrocyclic Reactions David Benbennick node Möbius Preserves Axis top touches bottom (odd # of nodes) requires twist in 1 of 2 ways Transition Preserves State Motion Mirror top touches top Hückel conrotation disrotation (even # of nodes) 6 5 4 3 2 1 4 3 ! 2 1 6 5 Track the MOs of hexatriene 4 they transform into those 3 of cyclohexadiene: 2 1 as 123 Möbius Aromatic Analogue (Hückel Connectivity) Preserves Axis Möbius Hückel conrotation disrotation 6 5 4 3 2 1 4 3 2 1 Preserves Mirror Hückel 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 CH3 CH3 +11 kcal/mole CH3 •• CH3 (less stable isomer) DH -16 kcal/mole CH3 CH3 CH3 CH3 (forms the less stable isomer) Disrotation preferred for 6-electron shift (4n+2) 4-electron cycloaddition! (less stable isomer) CON 4e DIS 6e 280°C CH3 H3C CH3 CH3 CH3 CH3 CH3 99.9% ~0.005% Bias >11 kcal/mole DIS for 4n+2 CH3 CH3 CH3 (forms the less stable isomer) CON for 4n CON 8e -10°C CH3 CH3 CH3 CH3 e.g. J&F Sec. 27.2 pp. 1343-1346 If you could run it forwards! 2 1 4e Möbius conrotation Transition State HOMO -1 bottom touches top (odd # of nodes) 6e Hückel disrotation top touches top (even # of nodes) Opening Dewar Benzene Strained Really wants to open up Stable (1866) 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! 4-electron disrotation! van Tamelen & Pappas (1963) 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 -11 kcal * LUMO HOMO conrotatory good for 4n electrons -75 kcal aromatic 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) 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 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) 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. 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