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

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.

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+

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:

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

Section 10.2b ( ) Addition of Cl 2, Br 2 (more unsymmetrical bridging)

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?

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

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

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.

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 ( )

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

49:48-54:24 Section 7.9C ( ) Stereochemistry

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 +

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

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)

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! + +

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

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

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 > sec Timing by competition with another process less strained But cis gives only cis

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 ( )

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

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

Rearrangement after Oxidation of BR 3 CH 3 R2BR2B O HO

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

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

Transition State HOMOs very similar Transition State LUMOs very similar

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

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