Chemistry 125: Lecture 51 February 14, 2011 Cycloaddition Epoxides Ozonolysis & Acetals CH 3 Li + O=CH 2 Analogy OsO 4 This For copyright notice see final page of this file Other Simultaneous Reagents Cl 2 C: (Carbene) R 2 BH (Hydroboration) CH 2 I 2 Zn/Cu (Carbenoid) O 3 (Ozonolysis) H-metal (Catalytic Hydrogenation) R-metal (Metathesis, Polymerization) RC (Epoxidation) OOHOOH O CH 2 H2CH2C H2CH2C O O O C H H All happen together with minimal atomic displacement (but not strictly in parallel) Wouldnt it have been simpler to abbreviate arrows as in textbooks? ( & are defined with respect to the plane of the peroxyacid nuclei) polyethers 3 to >20,000 units (solvents) or H+H+ H + Catalysis H2CH2CCH 2 O HO - 20,000,000 tons $20 billion per year H2CH2CCH 2 O ethylene glycol (antifreeze, solvents, polymers) e.g. J&F Sec. 10.4c pp H2CH2CCH 2 HO OH H2OH2O of which 2/3 H2CH2CCH 2 O HO - Catalysis H2CH2CCH 2 O H + H2CH2C HO OH H2OH2O - HO - H2OH2O H2CH2CCH 2 HO OH - H + ring strain good leaving group Org Syn Prep (click) OH H2CH2CCH 2 -O-O Cl - K + Regiospecificity 55 / 45 = E a = 0.12 kcal/mole Protonated Isobutylene Oxide 1.471.61 worst place for H + best place for Nu - Cuprates (Carbon Nucleophiles) Stereospecificity More Impressive Regiospecificity J&F sec 10.5c 430 Ozonolysis by Cycloadditions e.g. J&F sec 10.5a Concerted Transition State (calc by quantum mech) H2CH2C CH 2 O O O + _ Motion along Reaction Coordinate through Transition State O3O3 C2H4C2H4 side viewend view HOMO LUMO HOMO Transition State Orbital Mixing makes two new bonds O3O3 C2H4C2H4 HOMO LUMO HOMO-1 Cycloaddition of Allylic 1,3-Dipoles to Alkenes 7 O O O + O O O + O O O + O O O + open structure of O 3 (Cf. Lecture 3) Ozone (O 3 ) from the top (rotate back at the top to view the 3 MOs made from the 3 allylic out-of-plane 2p orbitals of the 3 O atoms) 1 No ABN (anti-bonding node) Middle AO is largest (it overlaps twice) 2 One ABN node. Middle AO is absent. No significant overlap, thus ~ same energy as isolated 2p AO. 3 Two ABNs - highest energy MO. (Im not sure why the middle AO looks about the same size as the terminal ones, it must be larger in order for 3 to be orthogonal to 1.) Another allylic system CH 2 -BH-CH 2 from top (rotate back to view 3 MOs) 1 (middle B AO about same size as C AOs; overlaps twice, but has lower nuclear charge) 2 Note how C AOs look larger than O AOs of O 3, because C AO is less dense near the nucleus) 3 Most of the lower-energy C AOs were used up in 1 and 2. 1 Partly C AO just looks big (but also C=O is short, which makes CO overlap important) 2 node no longer in exact center 3 BIG C AO for this high- energy MO H 2 C=O O + - carbonyl oxide pOpO C=O * C=O Central O overlaps C better than O, so view as right O interacting weakly with C=O orbitals. 11 22 33 more mixing (better E-match) less mixing pOpO pCpC * - p O - p O + p O - p O * - p O .. Number of electrons LUMO HOMO LUMO (ends match * alkene LUMO) (ends match alkene HOMO) (ends match alkene HOMO) (No alkene HOMO match) (No alkene LUMO match).. Cant make two bonds simultaneously for cycloaddition to alkene!.. HOMO LUMO (ends match * alkene LUMO) * * Dont worry about apparent bad overlap with the blue lobe of the central oxygen. It is far enough away because of the bend in O 3. O O O 4 C B C H HH H H H O O H C Makes two bonds CH 2 H2CH2C O O O + Ozonolysis e.g. J&F Section 10.5a, pp O CH 2 H2CH2C O O : Undergoes a reverse of the previous process. Molozonide is rather unstable because of HOMO-HOMO mix in -O-O-O- group. Ozonolysis CH 2 O O H2CH2C O + O Undergoes a reverse of the previous process. to give carbonyl oxide and C=O Re-adds after rotation (avoids -O-O-O-) Ozonolysis CH 2 O-O O H2CH2C Ozonide a Double Acetal Ozonolysis Process? Mechanism for Acid-Catalyzed Hydrolysis of Acetal RO CH 2 + H HOH : : RO CH 2 + HROH RO-CH 2 + HO RO CH 2 + H First remove RO, and replace it by HO. HO RO CH 2 Now remove second RO, then H (from HO) : HO RO CH 2 + H RO=CH 2 + cation unusually stable, thus easily formed ROH H-O-CH 2 + O=CH 2 ROH : Overall Transformation: H 2 O + Acetal Carbonyl + 2 ROH H+H+ (e.g. J&F pp ) (hemiacetal) Process? SN1SN1 E1 + H O H H CH 2 RO HOHO O=CH 2 CH 2 HO-O O H H O-O O H2CH2C O H H H H H 2 C=O Ozonide is a Double Acetal So Double Hydrolysis and hydrogen peroxide Gives Two Carbonyl Compounds which oxidizes aldehydes to carboxylic acids! Ozonolysis e.g. J&F Sec. 10.5b pp Add a reducing agent like (CH 3 ) 2 S (or Zn) to destroy HOOH and save RCH=O. Or go with the flow and add more HOOH to obtain a good yield of RCOOH. Ozonolysis 3-membered ring with O-O bond is even worse. What Happens to HOOH + RCHO? O C H R O OH - O C H R O - O C H R O - HOH - O CR O R B R R O OH - Cf. Problem: Try drawing an analogous acid-catalyzed mechanism in which HOOH attacks the protonated carbonyl, then H + is lost from one O of the HOOH fragment in the product and added to the other before rearrangement. OH OH - is a bad leaving group from C, but O-O bond is very weak. Hydride Shift Nucleophilic Addition to C=O The nucleophilic addition of methyl lithium to carbonyl groups* is formally quite different from these additions of electrophiles to alkenes, but the following transition state analysis reveals a marked mechanistic similarity. * which will be discussed in more detail later. Transition State Motion Li-CH 3 O=CH 2 Li CH 3 O CH 2 Transition State Orbital Mixing Li-CH 3 O=CH 2 HOMOLUMO+2 * LUMO HOMO Orbital Variety from Metals overlaps with alkene *overlaps with alkene LUMOHOMO Os or Mn - OsO 4 and Permanganate e.g. J&F Sec. 10.5c p. 443 OsO 4 and Permanganate Os analogue of cyclic acetal H-O-H e.g. J&F Sec. 10.5c p. 443 Osmate Ester H H C C H3CH3C CH 3 H H C C H3CH3C OO O O Os O O OO O HH Abigail Batchelder End of Lecture 51 February 14, 2011 Copyright J. M. McBride 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).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. 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