Transcript No Slide Title

How Do You Hydrate a Double
Bond?
H2O
R
CH
CH2
H+
R
CH
CH3
OH
The problem with this approach is that yields
are low, and carbocation rearrangements can
complicate the results.
We need a better approach!
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Oxymercuration of an Alkene
Hg(OCOCH3)2
R
CH
CH 2
R
CH
H2O
CH 2 Hg(OCOCH 3)
OH
•Yields are high, there are no
rearrangements, and the conditions
are milder.
NaBH4
•The sodium borohydride reduces the
mercury to Hg0.
NOTE: The product is the same one that
would be obtained if you added water
across the double bond according to
Markovnikov’s Rule!
R
CH
CH 2 H
OH
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Mechanism of Oxymercuration
OCOCH 3
slow
Hg
OCOCH 3
H
H
Hg
+
+
OCOCH 3
_
CH3COO
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Step 2...
H
..
O
..
H
H
+
-H
H
Hg
+
H
OCOCH 3
:O :
H
H
Hg
OCOCH 3
or
H
..
O
H
..
Hg
OCOCH 3
H
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This is the
only opening
for the
nucleophile.
Approach from
the bottom is
blocked.
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Reduction
H
H
:O :
:O :
H
H
Hg
H
OCOCH 3
H
NaBH4
or
H
+
or
Hg
(ppt)
H
H
..
O
H
..
Hg
OCOCH 3
H
H
..
O
..
H
H
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H
CH 3
CH 3
H
slow
Hg(OCOCH3)
2
CH 3
CH 3
H2O
O
Hg
+
H
25° C
OCOCH 3
H
H
:
O
..
H
H
CH 3
CH 3
+
-H
H
CH 3
OH
CH 3
H
Hg
+
OCOCH 3
Hg
OCOCH 3
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H
H
H
CH 3
OH
NaBH4
H
OCOCH 3
OH
CH 3
CH 3
Hg
CH 3
H
• This is equivalent to Markovnikov addition of
water across the double bond.
• Note that the -OH and the -H are anti to one
another.
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… but what if you want the
isomeric alcohol?
how???
R
CH
CH2
R
CH2 CH2 OH
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Hydroboration of an Alkene
BH3
R
CH
CH2
R
CH2 CH2
B
3
a trialkylborane
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Borane
H
B
H
H
This is not stable under ordinary
conditions, so we have to generate it within
the reaction -- “in situ”
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Preparation of Diborane
3 NaBH4 + 4 BF3
H
H
B
H
2 B2H6 + 3 NaBF4
H
H
B
ether
H
2
H
B
H
H
Diborane
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R
CH
CH 2
+

CH
R
BH3
CH 2
H
B

H
H
R

CH
CH 2
H
B
R
CH
CH 2
R
H

CH 2 CH
CH
CH 2 BH 2
H
R
Notice the “anti-Markovnikov”
orientation of addition!
H
Regioselective
R
CH
CH 2
R
B
H
2
H
CH
CH 2
R
CH
CH 2
B
H
3
a trialkylborane
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Stereochemistry of
Hydroboration
CH 3
CH 3
H
H
BH 2
H
H
BH 2
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•We can prepare a wide variety of organoboranes
by this method.
•But now: we made an organoborane -- what can
we do with it?
•Boron has a strong affinity for oxygen -- it forms
a very strong B-O bond. When we react the
organoborane with oxygen-containing
compounds, we can obtain new organic products.
•For example: the reaction of an organoborane
with a carboxylic acid yields a reduction product.
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Hydroboration - Protonolysis
R
B
CH2 CH 2
3
R
CH 2 CH 3
3
+
+
O
3 CH3 C
(CH3COO)3B
OH
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Examples of Hydroboration-Protonolysis
1) BH3
3 CH3 CH2 CH2 CH
CH2
3
2) CH3COOH
CH3 CH2 CH2 CH2 CH3
1) BH3
3
3
2) CH3COOH
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“Mechanism” of Protonolysis
R
CH2 CH2 B
R
CH2 CH2
H
O
H
B
C
O
+
CH3
O
C
O
CH3
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Stereochemistry of Hydroboration-Protonolysis
CH 3
BH3
CH 3
CH 3
B
CH 3
H
CH3COOH
Notice that the two
hydrogens are syn
to one another!
CH 3
CH 3
H
H
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DO YOU REMEMBER OUR ORIGINAL
QUESTION? HOW DO YOU DO THIS?
how???
R
CH
CH2
R
CH2 CH2 OH
Another variation on the decomposition of
organoboranes with oxygen-containing compounds is
to perform the oxidation with an alkaline solution of
hydrogen peroxide.
The reaction, in this case, is an oxidation, and the
principal products are alcohols.
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Hydroboration - Oxidation
R
CH 2 CH2
+
3 H2O2
B
3
_
3
R
CH 2 CH2 OH
OH
+
B(OH)3
The product is an alcohol, but in this case it
is the regioisomer of the one obtained by
hydration of an alkene or by oxymercuration.
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(R
)
CH 2 CH 2 B
3
R
+
_
OOH
R
R
CH 2 CH 2
_
CH 2 B
O
R
CH 2
R
CH 2 CH 2 O
CH 2
CH 2 CH 2
_
CH 2 B
O
R
CH 2 CH 2
_
OOH
O
R
H
CH 2 CH 2 B
R
CH 2 CH 2 O
CH 2 CH 2 B
O
+
_
OH
CH 2 CH 2
Each addition is a syn addition
CH 2 CH 2
R
H
CH 2 CH 2
R
_
- OH
R
R
O
O
_
OOH
_
- OH
(R
)
CH 2 CH 2 O
3
a trialkoxyborane
H2O
B
_
3
R
CH 2 CH 2 OH
OH
+
B( OH )3
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Stereochemistry of Hydroboration-Oxidation
CH 3
BH3
CH 3
CH 3
B
CH 3
H
_
H2O2/OH
The product is formed with
syn stereospecificity.
CH 3
CH 3
OH
cis-1,2-Dimethylcyclopentanol H
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Methods of Hydrating an Alkene
R
CH
CH2
R
CH
CH3
OH
H2O + H2SO4:
follows Markovnikov’s Rule
Hg(OCOCH3)2, H2O, followed by NaBH4:
follows Markovnikov’s Rule
R
CH
CH2
B2H6, followed by H2O2 and OH-:
R
CH2 CH2 OH
gives an apparent “antiMarkovnikov” product
NOTE: Each of these reactions is regioselective!
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If you go back and analyze the mechanism of
hydroboration, you will find that the reaction
actually does follow an expanded
Markovnikov’s Rule.
The Lewis acid (the species that adds first)
does indeed add to the carbon with the greater
number of hydrogens.
The difference here is that the Lewis acid is
boron. Hydrogen, in this reaction, is acting as
a base (nucleophile)!
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Summary of Hydroboration
Reactions
R
C
H
H
H
H
R
BH3
C
H
C
H
C
H
B
H
H
_
H2O2/OH
CH3COOH
Each of these
additions is
stereospecifically a
syn addition.
H
H
H
H
R
C
H
H
R
C
C
H
H
H
C
OH
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The hydroboration reactions were discovered by Prof.
Herbert C. Brown (Purdue University - emeritus)
Brown’s achievements, focused principally on his
discovery of hydroboration, have contributed to the
well-being of humankind -- thus, he earned the Nobel
Prize in Chemistry in 1979.
Hydroboration, and the reagents that have been
developed from these basic methods, have been very
useful in the synthesis of important organic
compounds, including pharmaceuticals.
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Hydroboration has also been used to develop new
chemical reagents. Among these are:
“Super Hydride” (lithium triethylborohydride) -- a very
powerful reducing agent
“Selectride” (lithium tri-sec-butylborohydride) -- a very
stereoselective reducing agent. Reductions with
Selectride give a predominance of one enantiomer
“9-BBN” (9-borabicyclo[3.3.1]nonane) -- a very efficient
hydroboration reagent.
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Preparation of 9-BBN
H
B
+ BH3
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Advantages of 9-BBN
CH
CH2
B2H6
CH2 CH2 B
Yield: 80%
9-BBN
CH
CH2
For each of these
organoboranes, the next step
would be oxidation with basic
hydrogen peroxide to yield the
corresponding alcohol.
CH2 CH2 B
Yield: 98.5% !!!
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Hydroboration-Protonolysis
of Alkynes
R
3
R
C
C
R'
+
BH3
R'
C
B
C
H
This reaction yields exactly the
same product that would be
obtained from hydrogenation by
the Lindlar method.
3
CH3COOH
R
To obtain the trans-alkene,
reduce the alkyne with sodium
in liquid ammonia.
R'
C
3
H
C
cis
H
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Hydroboration - Oxidation
of Alkynes
R
3
R
C
C
R' +
BH3
R'
C
B
C
H
3
_
H2O2/OH
R
R'
C
3
H
C
OH
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But….
R
H
C
R
C
H
OH
enol
H
O
C
C
H
H
TAUTOMERISM !!!keto
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Aldehydes are formed by the hydroborationoxidation of alkynes,
Whereas,
Hydration of an alkyne with H2O, H2SO4, and HgSO4
produces ketones.
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