1. 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

2. 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

3. CH 2 H2CH2C H2CH2C O O O C H H All happen together with minimal atomic displacement (but not strictly in parallel)     Wouldn’t it have been simpler to abbreviate arrows as in textbooks?    (  &  are defined with respect to the plane of the peroxyacid nuclei)

4. 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. 427-430 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 +

5. Regiospecificity 55 / 45 = 10 0.09  E a = 0.12 kcal/mole

6. Protonated Isobutylene Oxide 1.47Å1.61Å +195 +79 +141.5 +140.2 worst place for H + best place for Nu -

7. Cuprates (Carbon Nucleophiles) Stereospecificity More Impressive Regiospecificity J&F sec 10.5c 430

8. Ozonolysis by Cycloadditions e.g. J&F sec 10.5a 436-439

9. Concerted Transition State (calc by quantum mech) H2CH2C CH 2 O O O + _

10. Motion along Reaction Coordinate through Transition State O3O3 C2H4C2H4 side viewend view

11. HOMO LUMO HOMO Transition State Orbital Mixing makes two new bonds O3O3 C2H4C2H4 HOMO LUMO HOMO-1

12. 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)

13. 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. (I’m 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.)

14. 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.

15.  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. 11 22 33 more mixing (better E-match) less mixing pOpO pCpC  * - p O  - p O  + p O  - p O  * - p O

16. .. 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).. Can’t make two bonds simultaneously for cycloaddition to alkene!.. HOMO LUMO (ends match  * alkene LUMO) * * Don’t 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 2 4 + H O O H C Makes two bonds

17. CH 2 H2CH2C O O O + Ozonolysis e.g. J&F Section 10.5a, pp. 436-439

18. 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

19. 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

20. CH 2 O-O O H2CH2C Ozonide a Double Acetal Ozonolysis

21. 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. 785-787) (hemiacetal) Process? SN1SN1 E1 + H O H H CH 2 RO

22. 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

23. e.g. J&F Sec. 10.5b pp. 440-441 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

24. 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

25. “Nucleophilic” Addition to C=O

26. 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.

27. Transition State Motion Li-CH 3 O=CH 2 Li CH 3 O CH 2

28. Transition State Orbital Mixing Li-CH 3 O=CH 2 HOMOLUMO+2  * LUMO  HOMO

29. Orbital Variety from Metals

30. overlaps with alkene  *overlaps with alkene  LUMOHOMO Os or Mn - OsO 4 and Permanganate e.g. J&F Sec. 10.5c p. 443

31. 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

32. Abigail Batchelder

33. End of Lecture 51 February 14, 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).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