Chemistry 125: Lecture 50February 11, 2011
Electrophilic Addition withNucleophilic Participation
CycloadditionEpoxides 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+
CH3 C C
CH3
OH
CH3
CH3
OH
CH3 C C
CH3
CH3
CH3
O+ H2O
CH3 C C
CH3
+CH3
CH3
OH
CH3 C C
CH3
+CH3
CH3
O H
Methide Shift
+Driving Force?
Other “Simultaneous” ReagentsCl2C: (Carbene)
R2BH (Hydroboration)
CH2I2 Zn/Cu (Carbenoid)
O3 (Ozonolysis)
H-metal (Catalytic Hydrogenation)
R-metal (Metathesis, Polymerization)
RC (Epoxidation)OOH
O
Simmons-Smith“Carbenoid”
Metal R-X Metal+
R-X
single-electrontransfer(SET)
e
Metal+
R X Metal
R-M X +
Zn Cu“couple”
CH2I2 + CH2
The next three slides suggest a plausible, but incorrect, two-step mechanism for addition of ICH2ZnI to H2C=CH2
Cl Zn CH3
Model forI-Zn-CH2I
4sZn
LUMO 4pZnLUMO + 1
bent for transition stateLUMO` 4spnZn
HOMO
Model forI-Zn-CH2I
LUMO`
Zn-CHOMO
Model forI-Zn-CH2I
Cl Zn CH3
CH2 CH2
Cl Zn CH3I Zn CH2 I
HOMOZn-C
LUMO
C-I
ZnI2CH2
“SN2”
If it were the diiodide instead of the model…
But these two transition states were just guessed, not calculated quantum mechanically…
Although the above two-step mechanism with intermediate IZnCH2-CH2-CH2I is plausible,
addition of IZnCH2I to H2C=CH2 probably 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
ICH2ZnIZn
I
I
ICH2ZnI
(at TransitionState Geometry)
LUMO
Mixes with HOMO
HOMO-2
Mixes with * LUMO
Zn
I
I
meta-chlorobenzoic acid
meta-chloroperoxybenzoic acid
Epoxidation by Peroxycarboxylic Acids
J&F sec 10.4a 423-425
+ +
mCPBA
25°C
81% yieldR = n-hexyl
benzene5 hr
?
LUMO
HOMO-3
200
0
-200
-400
Orb
ital E
nerg
y (k
cal/m
ole)
UMOs
OMOs
etc.
Peroxyformic AcidDistorted to
Transition State for O Transfer
p(O
*O-O
“-allylic”
CH2
H2CCH2
H2C
O
OO C
H
H
“SN2 at O”
“-allylic” resonance
p()O
nucleophile(nearby)
*O-O electrophile
All happen together with
minimal atomic displacement
carboxylate “leaving group”
(but not strictly in parallel)
C-C nucleophile
pC+
electrophile
*H-O+
electrophile
“SN2 at H”backside
attack
Transition State
GeometryO-O
Strongly Stretched(from ~1.5Å)
O-HHardly
Stretched(from ~1Å)
kH/kD ~ 1
Coplanar“Butterfly”
mechanism(not spiro)
suggested by Paul D. Bartlett
(1950)
calculatedJ. Amer. Chem. Soc. (1991) pp. 2338-9
downhill motionafter TS
Only one TS :
“Concerted but not Synchronous”
“spiro” meanstwo perpendicular
rings sharing a common atom
(here O1)
Note that arrows were not used as carefully
in those days.
Bartlett 1950
Problem:How about now?
(compare arrows in this textbook illustration with the mechanism on
the previous frames and try drawing a more accurate diagram)
Stereospecificity of Epoxidation:Concerted Syn Addition
Pasto & Cumbo 1965
~0°C 10 hr
HH
C C
H3CCH3
O
>99.5% trans
mCPBAH
HC C
H3C
CH3
trans
O O
52-60% yield
O O
mCPBA
H HC C
H3C CH3
cis>99.5% cis
H H
C CH3C CH3
O
~0°C 10 hr 52-60% yield
Alternative Epoxide Preparation (1936)
H2O< 0°C3 hr
H HC C
H3C CH3 HOCl
Wilson & Lucas 1936
H H
C CH3C CH3
Cl+ H
H
C C
CH3
CH3
Cl
HO
55% yield(distilled)
SN2
H2O
H2O90°C2 hr
KOH(20M)
H
H
C C
CH3
CH3
Cl
-O
H HC CH3C CH3
O90% yield
45% over two steps
syn
inversion
2nd inversion
CH2CHO
HCC
H
OH
CH2
H
OR
ORO
OEtO
O CO2Et
TiRO
O
Remember Sharpless Asymmetric Epoxidation
R
ROO ••
RO+Ti
O
O
O
R
OEtO
CO2Et
O
RO
Ti
O
O
O OEtO
CO2Et
*
RCH2
HC
CCH
H
allyl alcohol
(R)-“epoxide”
(S)-epoxide precursor
Chiral“Oxidizing Agent”
LUMO?
HOMO?
is diastereomeric!
( also pO + *C=C )
Cf. J&F Sec. 10.4b p. 426
20,000,000 tons$20 billion
per year
OLDCAMPUS
H2C CH2
O H2C=CH2 + O2
Ag
250°C15 atm
ethylene oxide
(84%)
Raising the yield by 5% would be
worth >$109/year.
*
* The rest oxidizes
to CO2/H2O.
Only 0.05% of ethylene oxide is used as such.
H+ Catalysis
H2C CH2
O
20,000,000 tons$20 billion
per year
H2C CH2
O
ethylene glycol(antifreeze, solvents,
polymers)
J&F Sec. 10.4c pp. 427-430
H2C CH2
HO
OH
H2O
of which 2/3
H2C CH2
O
HO- Catalysis
End of Lecture 50February 11, 2011
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