1. Chemistry 125: Lecture 49 February 9, 2011 Electrophilic Addition with Nucleophilic Participation This For copyright notice see final page of this file

2. Problem: Suggest a Multi-Step Mechanism for the Acid-Catalyzed “Pinacol Rearrangement” (draw nice curved arrows) H+H+ CH 3 CC OH CH 3 OH CH 3 CC O “Pinacol”“Pinacolone” + H 2 O The name was coined in 1859 from “pinax”, Greek for “tablet”, because of the shape of crystals of its hydrate.

3. An Alternative: Oxymercuration Reduction 2° Cation + CH 3 CCH CH 3 3° Cation (more stable) CH 3 CCH CH 3 + CCH CH 2 CH 3 HO CH 3 CCH CH 3 H 2 O -H + H Catalyzed Hydration is Subject to Rearrangement +H+H+

4. Oxymercuration Reduction CH 3 CCH CH 2 CH 3 2) NaBH 4 1) Hg(OAc) 2 H 2 O HO CH 3 CCH CH 3 CCH CH 3 OH CH 3 Avoids Rearrangement when Adding HOH An Alternative:

5. Larger than H +, Hg +2 can overlap with both carbons to give a single minimum and inhibit rearrangement. Subsequent reduction by BH 4 - completes Markovnikov hydration without rearrangement. But the bridge is unsymmetrical, with weaker bonding to the more substituted carbon. + CHR H2CH2C HgOAc + H2CH2C CHR HgOAc + H2CH2C CHR HgOAc Hg(OAc) 2 H2CH2C CHR + H2CH2C HgOAc H2OH2O H O H CHR H2CH2C HgOAc OH -H + NaBH 4 CHR H2CH2C H OH

6. Section 10.2b (414-421) Addition of Cl 2, Br 2 (more unsymmetrical bridging)

7. electrophile LUMO (  *) Ethylene HOMO (  ) bonding antibonding + - HOMO (p) (where the  Cl-Cl electrons went) HOMO-2 (where the  electrons went) Chlorine Two Cl-C Bonds? Cl 2 is an “oxidizing agent” removes e - from alkene poor overlap Where are HOMO & HOMO-1?

8. LUMO (  *) nucleophile HOMO (  *) Ethylene + - HOMO-1 ! Chlorine : Where are HOMO & HOMO-1?

9. LUMO - HOMO-1 HOMO (unshared pair on Cl) + -

10. LUMO + - H2CH2C CH 2 :Cl Cl Cl - H2CH2C CH 2 Cl + H2CH2C CH 2 Cl “Electrophilic” Addition of Cl 2 to an alkene is both electrophilic and nucleophilic simultaneously.

11. Halohydrins H2CH2C CH 2 :Cl Cl Cl - H2CH2C CH 2 Cl + H2CH2C CH 2 Cl O-H H + + H : : H O H J&F Section 10.2b (417-420)

12. Br - H2OH2O Bromonium Regiochemistry How do we know the ion is bridged? “Halohydrin” shows Markovnikov Regiochemistry (like oxymercuration) t-Bu H C C H3CH3C H H C C H3CH3C H Br + Br 2 J&F p. 420 Unsymmetrical Bridged Bromonium Ion t-Bu H C C CH 3 H Br 24% 60% -H + t-Bu H C C CH 3 H Br HO SN2SN2

13. 49:48-54:24 Section 7.9C (308-311) Stereochemistry

14. H2OH2O Bromonium Stereochemistry H 2 O attacks  * C-Br from backside. (Unbridged C + would have been attacked from both sides.) Anti Addition J&F p. 419 HH H H Br + Br 2 trans bromohydrin HO H Br H -H +

15. 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

16. Jack Hine, Ph.D. (1950) “about as earthy a research project as could be appropriate for a postdoctoral”  -Elimination Carbenes X 2 C:X3CX3C X 3 C HO-C(CH 3 ) 3 K+K+ ( X = Cl,Br ) X Reaction of CH n Cl 4-n with HO - CH 3 Cl CH 2 Cl 2 CHCl 3 CCl 4 fastslowv.slowfast Reaction of CH n Cl 4-n with PhS - fast slowv. slow base nucleophile J&F Section 10.4d (431-2)

17. C C H H H H LUMO HOMO C Cl Most reactions in this lecture use analogous LUMOs and HOMOs to mix with the  HOMO and  * LUMO of H 2 C=CH 2, respectively, so as to form two bonds simultaneously. But both HOMO/LUMO & LUMO/HOMO pairs are orthogonal! + +

18. Transition State Motion for F 2 C: + H 2 C=CH 2 shrinking rotating stretching

19. LUMO F 2 C: H 2 C=CH 2 Transition State F 2 C: + H 2 C=CH 2 HOMO LUMO

20. How do we know both bonds form at once? H H C C H3CH3C CH 3 CBr 2 H H C C H3CH3C CH 3 CBr 2 cis H H C C H3CH3C CH 3 C Br 2 H H C C H3CH3C CH 3 CBr 2 rotate about single bond H H C C H3CH3C CH 3 C Br 2 trans if this intermediate lasts >10 -10 sec Timing by competition with another process less strained But cis gives only cis

21. Hydroboration / Oxidation Adds H OH CH 3 H H BR 2 H CH 3 H OH H H BR 2 HOOH OH - J&F Sections 9.10-9.11 (390-401)

22. Transition State Motion for BH 3 + H 2 C=CHCH 3 shrinking stretching rotating

23. HOMO Transition State BH 3 + propene (distorted) BH 3 (distorted) C 3 H 6 HOMO LUMO + 3 LUMO

24. Rearrangement after Oxidation of BR 3 CH 3 R2BR2B O HO

25. Subsequent CH 3 BH 2 -O-OH rearrangement is like S N 2 Cl -  * C-Br CH 3 R2BR2B O HO  * O-O  B-C

26. Subsequent CH 3 BH 2 -O-OH rearrangement is like S N 2

27. Transition State HOMOs very similar Transition State LUMOs very similar

28. Why do Hydroboration/Oxidation if it just adds H and OH to C=C? Alcohol Product is syn (H,OH from same face of C=C) and “anti-Markovnikov” (less substituted at C-OH) ! Contrast with acid-catalyzed hydration CH 3 H H BR 2 H CH 3 H OH H H BR 2 HOOH OH - replaces BR 2 regiochemistry? stereochemistry? location of OH? CH 3 H H OH Random

29. End of Lecture 49 February 9, 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