Chemistry 125: Lecture 51February 14, 2011

CycloadditionEpoxides

Ozonolysis & AcetalsCH3Li + O=CH2 Analogy

OsO4 This

For copyright notice see final page of this file

Other “Simultaneous” ReagentsCl2C: (Carbene)

R2BH (Hydroboration)

CH2I2 Zn/Cu (Carbenoid)

O3 (Ozonolysis)

H-metal (Catalytic Hydrogenation)R-metal (Metathesis, Polymerization)

RC (Epoxidation)OOH

O

CH2

H2CCH2

H2C

O

OO 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)

polyethers – 3 to >20,000 units(solvents)

orH+ H+ Catalysis

H2C CH2

O

HO- 20,000,000 tons

$20 billionper year

H2C CH2

O

ethylene glycol(antifreeze, solvents,

polymers)

e.g. J&F Sec. 10.4c pp. 427-430

H2C CH2

HO

OH

H2O

of which 2/3

H2C CH2

O

HO- Catalysis

H2C CH2

O H

+

H2C CH2

HO

OH

H2O

- HO-

H2O

H2C CH2

HO

OH

- H+

ring strain

good leaving group

Org Syn Prep(click) Cl

Cl

- K+

- K+

Regiospecificity

55 / 45 = 100.09

Ea = 0.12 kcal/mole

Protonated Isobutylene Oxide

1.47Å1.61Å

+195

+79

+141.5 +140.2

worst place for H+

best place for Nu-

Cuprates (Carbon Nucleophiles)

Stereospecificity

More ImpressiveRegiospecificity

J&F sec 10.5c 430

Ozonolysis by Cycloadditions

e.g. J&F sec 10.5a 436-439

ConcertedTransition State

(calc by quantum mech)

H2C CH2

O O O+

_

Motion along Reaction Coordinate through Transition State

O3

C2H4

side view end view

HOMO

LUMO

HOMO

Transition StateOrbital Mixing

makes two new bonds O3

C2H4

HOMO

LUMO

HOMO-1

Cycloaddition ofAllylic 1,3-Dipoles to Alkenes

7. (5 min) Having learned that the allylic system of O3 forms two bonds at once to an alkene, as shown below, one might think to try the same thing with the apparently analogous boron compound (assuming it exists). Explain in terms of the orbitals involved why this might not be such a good idea.

O

O

OO

O

O

H2

C

B

C H2

B

C H3

C H3

?

7

OO

O+

OO

O+

OO

O

+

OO

O+

open structure of O3 (Cf. Lecture 3)

Ozone (O3) 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.)

Another allylic systemCH2-BH-CH2 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 O3,

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)

2node no longer in

exact center

3BIG C AO

for this high-energy MO

H2C=O O+ -

“carbonyl oxide”

pO

C=O

*C=O

Central O overlaps C better than O, so view as right O interacting weakly with C=O orbitals.

1

2

3

more mixing(better E-match)

less mixing

pO

pC

* - pO

- pO

+ pO + pO

- pO

* - pO

..

..

Number of

electrons

LUMO

HOMO

HOMO

LUMO

(ends match *alkene LUMO)

(ends match alkene HOMO) (ends match

alkene HOMO)

(No alkeneHOMO match)

(No alkeneLUMO 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 O3.

OO

O

4C

BCH

H HH

H 2 4+

H

OO

H C

Makes two bonds Makes two bonds

CH2

H2C OO O

+

Ozonolysis

e.g. J&F Section 10.5a, pp. 436-439

O

CH2

H2C OO:

Undergoes a “reverse” of the

previous process.

“Molozonide” is rather unstable because of HOMO-HOMO mixin -O-O-O- group.

Ozonolysis

CH2O

OH2C

O+

OCH2

Undergoes a “reverse” of the

previous process.

to give carbonyl oxide

and C=ORe-adds after rotation

(avoids -O-O-O-)

Ozonolysis

CH2

O-O

OH2C

Ozonidea Double Acetal

Ozonolysis

Process?

Mechanism for Acid-Catalyzed Hydrolysis of Acetal

RO

ROCH2

+H HOH

:

:

RO

ROCH2

+ H ROH

RO-CH2

+

HO

ROCH2+

H

First remove RO, and replace it by HO.

HO

ROCH2

Now remove second RO, then H (from HO)

:HO

ROCH2

+ H

RO=CH2

+

cation unusually stable,thus easily formed

ROH

H-O-CH2

+

O=CH2 O=CH2

ROH

ROH

:Overall Transformation:

H2O + Acetal Carbonyl + 2 ROHH+

(e.g. J&F pp. 785-787)

(hemiacetal)

Process?SN1

E1

+H

OH

HCH2

RO

RO

HOO=CH2CH2

HO-OO

H

H

O-O

OH2C O

H

H H

HH2C=O

Ozonide is a Double AcetalSo Double Hydrolysis

and hydrogen peroxide

Gives Two Carbonyl Compounds

which oxidizes aldehydes to carboxylic acids!

Ozonolysis

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

Add a reducing agent like (CH3)2S (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?

OCH

R

O OH-OH

O

CH

R

O

- OC

H

R

O OH-

HOH

-

OCR

OR

BR

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.

OHOH- is a bad leaving group from C,

but O-O bond is very weak.Hydride Shift

“Nucleophilic”Additionto 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 StateMotion

Li-CH3

O=CH2

Li CH3

O CH2

Transition StateOrbital Mixing

Li-CH3

O=CH2

HOMOLUMO+2

* LUMO HOMO

Orbital Varietyfrom Metals

overlaps with alkene *overlaps with alkene

LUMOHOMO

Os or Mn-

OsO4 and Permanganatee.g. J&F Sec. 10.5c p. 443

OsO4 and Permanganate

Os analogueof

cyclic acetal

H-O-H

e.g. J&F Sec. 10.5c p. 443

Osmate Ester

H

HC C

H3C

CH3

HH

C C

H3CCH3

O O

OOOs

OOOs

OOOH H

Abi

gail

Bat

chel

der

End of Lecture 51February 14, 2011

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