How Do You Hydrate a Double Bond?

1. 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

2. Oxymercuration of an Alkene • 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 Markovnikov’s Rule! WWU -- Chemistry

3. Mechanism of Oxymercuration WWU -- Chemistry

4. Step 2... WWU -- Chemistry

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

6. Reduction WWU -- Chemistry

7. WWU -- Chemistry

8. 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

9. … but what if you want the isomeric alcohol? WWU -- Chemistry

10. Hydroboration of an Alkene WWU -- Chemistry

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

12. Preparation of Diborane Diborane WWU -- Chemistry

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

14. Stereochemistry of Hydroboration WWU -- Chemistry

15. 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

16. Hydroboration - Protonolysis WWU -- Chemistry

17. Examples of Hydroboration-Protonolysis WWU -- Chemistry

18. “Mechanism” of Protonolysis WWU -- Chemistry

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

20. 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

21. 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

22. Each addition is a syn addition WWU -- Chemistry

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

24. Methods of Hydrating an Alkene H2O + H2SO4: follows Markovnikov’s Rule Hg(OCOCH3)2, H2O, followed by NaBH4: follows Markovnikov’s Rule B2H6, followed by H2O2 and OH-: gives an apparent “anti- Markovnikov” product NOTE: Each of these reactions is regioselective! WWU -- Chemistry

25. 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

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

27. 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. WWU -- Chemistry

28. 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

29. Preparation of 9-BBN WWU -- Chemistry

30. 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

31. Hydroboration-Protonolysisof 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

32. Hydroboration - Oxidationof Alkynes WWU -- Chemistry

33. But…. TAUTOMERISM !!! WWU -- Chemistry

34. Aldehydes are formed by the hydroboration-oxidation of alkynes, Whereas, Hydration of an alkyne with H2O, H2SO4, and HgSO4 produces ketones. WWU -- Chemistry