1. Chemistry 125: Lecture 50 February 12, 2010 More Electrophilic Addition to Alkenes with Nucleophilic Participation This For copyright notice see final page of this file

2. Although the above two-step mechanism with intermediate IZnCH 2 -CH 2 -CH 2 I is plausible, addition of IZnCH 2 I to H 2 C=CH 2 actually occurs in a single step, according to quantum mechanical calculation*, with the bent transition state shown below: * A DFT Study of the Simmons-Smith Cyclopropanation Reaction. A. Bottoni, et al., J. Am. Chem. Soc, 1997, 119, 12300

3. ICH 2 ZnI Zn I I

4. ICH 2 ZnI (at Transition State Geometry) LUMO Mixes with  HOMO HOMO-2 Mixes with  * LUMO Zn I I

5. Epoxidation by Peroxycarboxylic acids (sec 10.4a 423-425 )

6. LUMO HOMO-3 200 0 -200 -400 Orbital Energy (kcal/mole)  OMOs etc. Peroxyformic Acid Distorted to Transition State for O Transfer p(  O  * O-O “  -allylic”

7. CH 2 H2CH2C H2CH2C O O O C H H “S N 2 at O” “  -allylic” “S N 2 at H” p(  ) O nucleophile  * O-O electrophile All happening together to give carboxylate “leaving group” (but not strictly in parallel)

8. Transition State Geometry O-O Strongly Stretched (from ~1.5Å) O-H Hardly Stretched (from ~1Å) k H /k D ~ 1 “Butterfly” mechanism (not spiro) suggested by Paul D. Bartlett (1950) calculated J. Amer. Chem. Soc. (1991) pp. 2338-9 downhill motion after TS Only one TS : “Concerted but not Synchronous” “spiro” means two perpendicular rings sharing a common atom (here O 1 )

9. Note that arrows were not used as carefully in those days. Bartlett 1950 Problem: How about now? (compare arrows with mechanism on previous frames and try drawing a more accurate diagram)

10. Concerted Syn Addition

11. CH 2 C H O H C C H OH CH 2 H OR O OEt O O CO 2 Et Ti RO O Remember Sharpless Asymmetric Epoxidation R ROO RO + Ti O O O R OEt O CO 2 Et O RO Ti O O O OEt O CO 2 Et ** R CH 2 H C C C H H allyl alcohol (R)-“epoxide”  (S)-epoxide precursor Chiral “Oxidizing Agent” LUMO? HOMO? is diastereomeric! ( also p O +  * C=C ) Cf. Sec. 10.4b p. 426

12. 20,000,000 tons $20 billion per year OLD CAMPUS H2CH2CCH 2 O H 2 C=CH 2 + O 2 Ag 250°C 15 atm ethylene oxide (84%)

13. 20,000,000 tons $20 billion per year H2CH2CCH 2 O ethylene glycol (antifreeze) polyethers (solvents) Sec. 10.4c pp. 427-430

14. Regiospecificity

15. Protonated Isobutylene Oxide 1.47Å1.61Å +195 +79 +141.5 +140.2

16. Cuprates (Carbon Nucleophiles) Stereospecificity More Impressive Regiospecificity

17. Ozonolysis by Cycloadditions (sec 10.5a 436-439 )

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

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

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

21. Cycloaddition of Allylic 1,3-Dipoles to Alkenes 7

22. Ozone (O 3 ) from the “top” (rotate back to view the 3  MOs from the 3 “allylic” out-of-plane 2p orbitals of 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 to be orthogonal to  1.)

23. 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.

24.  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”  + p O  - p O  * - p O pOpO  CO  * CO Central O overlaps C better than O, so consider right O interacting weakly with C=O orbitals. 11 22 33 more mixing (better E-match) less mixing

25. .. 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

26. CH 2 H2CH2C O O O + Ozonolysis (Text Section 10.5a, pp. 436-439)

27. O CH 2 H2CH2C O O : Undergoes a “reverse” of the previous process. “Molozonide” is rather unstable because of -O-O-O- group’s HOMO-HOMO mix.

28. 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-)

29. CH 2 O-O O H2CH2C Ozonide a Double Acetal

30. 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) + H : HO RO CH 2 + H RO=CH 2 + cation unusually stable; thus easily formed ROH H-O-CH 2 + O=CH 2 ROH RO CH 2 O H H  : Overall Transformation: H 2 O + Acetal Carbonyl + 2 ROH H+H+ (pp. 785-787) (hemiacetal)

31. End of Lecture 50 Feb. 12, 2010 Copyright © J. M. McBride 2010. 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