WWU -- Chemistry How Do You Hydrate a Double Bond? 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 Yields are high, there are no rearrangements, and the conditions are milder. The sodium borohydride reduces the mercury to Hg 0. NOTE: The product is the same one that would be obtained if you added water across the double bond according to Markovnikov’s Rule!

WWU -- Chemistry Mechanism of Oxymercuration

WWU -- Chemistry Step 2...

WWU -- Chemistry Approach from the bottom is blocked. This is the only opening for the nucleophile.

WWU -- Chemistry Reduction

WWU -- Chemistry

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?

WWU -- Chemistry Hydroboration of an Alkene

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

WWU -- Chemistry Preparation of Diborane Diborane

WWU -- Chemistry Notice the “anti-Markovnikov” orientation of addition! Regioselective

WWU -- Chemistry Stereochemistry of Hydroboration

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

WWU -- Chemistry Examples of Hydroboration-Protonolysis

WWU -- Chemistry “Mechanism” of Protonolysis

WWU -- Chemistry Stereochemistry of Hydroboration-Protonolysis Notice that the two hydrogens are syn to one another!

WWU -- Chemistry DO YOU REMEMBER OUR ORIGINAL QUESTION? HOW DO YOU DO THIS? 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 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 Each addition is a syn addition

WWU -- Chemistry Stereochemistry of Hydroboration-Oxidation The product is formed with syn stereospecificity. cis-1,2-Dimethylcyclopentanol

WWU -- Chemistry Methods of Hydrating an Alkene H 2 O + H 2 SO 4 :follows Markovnikov’s Rule Hg(OCOCH 3 ) 2, H 2 O, followed by NaBH 4 :follows Markovnikov’s Rule B 2 H 6, followed by H 2 O 2 and OH - : gives an apparent “anti- Markovnikov” 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 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)!

WWU -- Chemistry Summary of Hydroboration Reactions Each of these additions is stereospecifically a syn addition.

WWU -- Chemistry 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 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

WWU -- Chemistry Advantages of 9-BBN For each of these organoboranes, the next step would be oxidation with basic hydrogen peroxide to yield the corresponding alcohol.

WWU -- Chemistry Hydroboration-Protonolysis of Alkynes 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.

WWU -- Chemistry Hydroboration - Oxidation of Alkynes

WWU -- Chemistry But…. TAUTOMERISM !!!

WWU -- Chemistry Aldehydes are formed by the hydroboration- oxidation of alkynes, Whereas, Hydration of an alkyne with H 2 O, H 2 SO 4, and HgSO 4 produces ketones.