How Do You Hydrate a Double Bond?

H2O R CH CH2 H
+

CH OH

CH3

The problem with this approach is that yields are low, and carbocation rearrangements can complicate the results. We need a better approach!

WWU -- Chemistry

Oxymercuration of an Alkene
Hg(OCOCH3)2 R CH CH2 R H2O CH CH2 Hg(OCOCH3) OH

Yields are high, there are no rearrangements, and the conditions are milder. 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 Markovnikovs Rule!

NaBH4

CH CH2 H OH

WWU -- Chemistry

Mechanism of Oxymercuration
OCOCH3 slow Hg OCOCH3 H Hg + + H OCOCH3

_ CH3COO

WWU -- Chemistry

Step 2...
H .. O .. H + -H H Hg + H OCOCH3 H Hg OCOCH3 H :O: H

or H .. O H .. Hg OCOCH3 H

WWU -- Chemistry

This is the only opening for the nucleophile.

Approach from the bottom is blocked.

WWU -- Chemistry

Reduction
H :O: H H :O: H

H or

Hg

OCOCH3 NaBH4

H or

H + H .. O .. H Hg (ppt)

H .. O H .. Hg OCOCH3 H H

WWU -- Chemistry

CH3 CH3

slow Hg(OCOCH3) 2 H2O

O

H CH3 CH3 H Hg + OCOCH3

25 C H H : O .. H CH3 CH3 H Hg + OCOCH3 + -H

H CH3

OH

CH3 Hg OCOCH3

WWU -- Chemistry

H CH3

H CH3

OH

NaBH4

OH

CH3 Hg OCOCH3 H

CH3

This is equivalent to Markovnikov addition of water across the double bond. Note that the -OH and the -H are anti to one another.

WWU -- Chemistry

 but what if you want the isomeric alcohol?

how??? R CH CH2 R CH2 CH2 OH

WWU -- Chemistry

Hydroboration of an Alkene
BH3 R CH CH2 R CH2 CH2 3 B

a trialkylborane

WWU -- Chemistry

Borane
H B H H

This is not stable under ordinary conditions, so we have to generate it within the reaction -- in situ

WWU -- Chemistry

Preparation of Diborane
3 NaBH4 + 4 BF3 ether 2 B2H6 + 3 NaBF4

H B H

H H B

H 2 H H

H B H

Diborane

WWU -- Chemistry

CH

CH2

BH3

CH H

CH2 B H H

CH H

CH2 CH2 CH H B H

CH

CH2 R CH H CH2 BH2

Notice the anti-Markovnikov orientation of addition! Regioselective

CH H

CH2

R B 2 H

CH

CH2

CH H

CH2

B 3

a trialkylborane

WWU -- Chemistry

Stereochemistry of Hydroboration
CH3 H

CH3 H BH2

H H BH2

WWU -- Chemistry

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.

WWU -- Chemistry

Hydroboration - Protonolysis
R CH2 CH2 3 + O 3 CH3 C OH + (CH3COO)3B B 3 R CH2 CH3

WWU -- Chemistry

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

WWU -- Chemistry

Mechanism of Protonolysis
R CH2 CH2 B R CH2 CH2 H O H O C CH3 B + O C O CH3

WWU -- Chemistry

Stereochemistry of Hydroboration-Protonolysis
CH3 CH3

BH3

CH3

CH3 H

CH3COOH

Notice that the two hydrogens are syn to one another!

CH3

CH3

H H

WWU -- Chemistry

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.

WWU -- Chemistry

Hydroboration - Oxidation
R CH2 CH2 + 3 H2O2 B 3 _ OH + B(OH)3 3 R CH2 CH2 OH

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.

WWU -- Chemistry

(R

CH2 CH2 B 3

_ OOH R

R CH2 R

CH2 CH2 _ CH2 B O CH2 CH2

R R R CH2

CH2 CH2 _ CH2 B O

_ OOH O H R

CH2 CH2 O +

CH2 CH2 B R

_ OH

CH2 CH2 O _ - OH

CH2 CH2

Each addition is a syn addition

_ OOH _ - OH

R R R

CH2 CH2 O

CH2 CH2 B CH2 CH2 O

(R

CH2 CH2 O

)
3

H2O B OH + B( OH )3 _ 3 R CH2 CH2 OH

a trialkoxyborane

WWU -- Chemistry

Stereochemistry of Hydroboration-Oxidation
CH3 BH3 CH3 CH3

CH3 H

The product is formed with syn stereospecificity.

CH3

H2O2/OH CH3

OH
cis-1,2-Dimethylcyclopentanol H

WWU -- Chemistry

Methods of Hydrating an Alkene

R CH CH2 R CH OH
H2O + H2SO4: Hg(OCOCH3)2, H2O, followed by NaBH4: follows Markovnikovs Rule follows Markovnikovs Rule

CH3

CH

CH2

CH2 CH2 OH

B2H6, followed by H2O2 and OH-:

gives an apparent antiMarkovnikov product

NOTE: Each of these reactions is regioselective!

WWU -- Chemistry

If you go back and analyze the mechanism of hydroboration, you will find that the reaction actually does follow an expanded Markovnikovs 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)!

WWU -- Chemistry

Summary of Hydroboration Reactions

R C H C H H H BH3 R C H H _ H2O2/OH C B H H H

CH3COOH

Each of these additions is stereospecifically a syn addition.

H R C H

H H C H R

H C H

H H C OH

WWU -- Chemistry

The hydroboration reactions were discovered by Prof. Herbert C. Brown (Purdue University - emeritus)

Browns 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.

WWU -- Chemistry

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.

WWU -- Chemistry

Preparation of 9-BBN
H B + BH3

WWU -- Chemistry

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% !!!

WWU -- Chemistry

Hydroboration-Protonolysis of Alkynes
R 3 R C C R' + BH3 H C C R' B 3 CH3COOH

This reaction yields exactly the same product that would be obtained from hydrogenation by the Lindlar method. To obtain the trans-alkene, reduce the alkyne with sodium in liquid ammonia.
3

R C H C

R'

cis
H

WWU -- Chemistry

Hydroboration - Oxidation of Alkynes

R 3 R C C R' + BH3 H 3 _ H2O2/OH R 3 H C C OH R' C C R' B

WWU -- Chemistry

But.
R C H enol C OH H R H C H O C H

TAUTOMERISM !!! keto

WWU -- Chemistry

Aldehydes are formed by the hydroborationoxidation of alkynes,

Whereas,

Hydration of an alkyne with H2O, H2SO4, and HgSO4 produces ketones.

WWU -- Chemistry