This page will deal with the following topics:

1. Acid Catalyzed Hydration of Alkenes
2. Oxymercuration-Demercuration of Alkenes
3. Hydroboration of Alkenes
4. Oxidation of Organoboranes
5. Reduction of Acyl (Carbonyl)Compounds
6. Organometallic Reaction On Aldehydes or Ketones
7. Organometallic Reactions On Epoxides

In an aqueous acid solution alkenes will add water across the Pi bond thereby saturating the molecule and producing an alcohol. The reaction is regioselective in that only the more highly substituted alcohol is produced. It follows the Markovnikov Rule. Molecular Rearrangement often occurs but not always which indicates that the reaction involves a carbocation intermediate. Molecular Rearrangements where a Hydrogen or a methyl group along with both electrons in the bond move over to an adjacent carbon in the molecule. This occurs only if it results in a more stable carbocation. Primary carbocations will rearrange to produce secondary or tertiary carbocations. Secondary carbocations undergo molecular rearrangement only if a tertiary carbocation results. Tertiary carbocations never undergo molecular rearrangement because of the highly stable nature of the tertiary carbocation. The reason that Markovnikov's Rule always results in the more substituted alcohol can be understood if one looks at the reaction mechanism proposed for this reaction.

1. CH₃-CH=CH₂ + H₂O + H⁺ --->CH₃-CH⁺CH₃
2. CH₃-CH⁺CH₃ + H₂O--->CH₃-CH(H₂O⁺)CH₃
3. CH₃-CH(H₂O⁺)CH₃ + H₂O ---> CH₃-CH(OH)CH₃ + H₃O⁺

The Hydrogen ion from the acid catalysts attaches itself to the organic molecule with the help of the Pi bonding electrons. The Hydrogen attaches itself to the carbon that will result in the most stable carbocation. In the next step the carbocation attaches itself to an Oxygen atom of a water molecule with the aid of a lone pair making the Oxygen atom positively charged, an Oxonium ion. In the final step, a water molecule pulls a Hydrogen ion off the Oxygen atom to produce the final alcohol. The obvious synthetic problem with this reaction is that it may undergo molecular rearrangement thereby producing more than one alcohol. In addition it always produces the more substituted alcohol so if you wanted another isomer, you wouldn't be able to use this reaction.

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This is actually two part synthesis. In the first part Mercury II Acetate, Hg(oAc)₂ will form a bridged species with the Mercury atom bridging the two sp2 carbons (See Fig 2 below).

Then in the second step a water molecule attaches itself to the least substituted of the sp2 carbons in the bridged ring intermediate with the aid of a lone pair on the Oxygen atom of the water molecule thus producing the Oxonium Intermediate and breaking the bridged structure. In a third step an acetate ion pulls a Hydrogen ion off the Oxygen to produce the Hydroxy Organo Mercury product. This constitutes the first part of the synthesis. In the second part, a strong reducing agent Sodium Borohydride in basic solution is added to the Mercury compound and the Mercury group is replaced by a Hydrogen atom to produce the final alcohol product. The reaction is regioselective producing only the more substituted alcohol like the Hydration reaction. It also follows Markovnikov's Rule. However, no molecular rearrangement is possible in this reaction indicating that no carbocation is produced. This is a distinct advantage over Acid Catalyzed Hydration giving less product mixing.

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The principal adding reagent in this reaction is BH₃,borane, but Borane is much too reactive to store in a bottle. Therefore Diborane is used in a Tetrahydrofuran solvent (THF). The Diborane cleaves and the resultsing Borane molecules are stabilized by complexing with the Oxygen atom in the cyclic ether, THF. Even Diborane is reactive enough to react in air resulting in a greenish flame. Even the Organoboranes will react with air so they must be kept in a suitable solvent like THF. The Borane adds across the Pi bond with one of the Hydrogens attaching to the more substituted sp2 carbon and the Boron attaching to the least substituted sp2 carbon (See Fig 3 below).

This is because the Boron being a larger atom needs more room and is less sterically hindered on the least substituted carbon. As long as the Boron has a Hydrogen attached to it this reaction will occur again with another alkene molecule until the Boron is attached to three alkene molecules producing the OrganoBorane.

Organoboranes are useful in themselves. They can be used to produce alkanes from alkenes by reduction of the Organoborane with acetic acid under reflux conditions. This replaces the Boron with a Hydrogen atom on each of the three organic groups attached to the Boron thus producing three molecules of Alkane for every one molecule of the Organoborane.

Alternatively, the Organoborane can be oxidized to produce an alcohol.

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Hydroboration followed by Oxidation will produce an alcohol. The reaction follows the Anti-Markovnikov Rule and the reaction is regioselective producing the least substituted alcohol. The reaction retains any configuration of the alkyl groups. The oxidation agent is Hydrogen Peroxide, H₂O₂ in basic solution. The reaction produces three alcohol molecules for every molecule of the Organoborane:

B(CH₃-C₂-CH₂)₃ + H₂O₂/OH^---->3 CH₃-C₂-CH₂-OH + BO₃^-

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An acyl compound is a compound that has a carbon doubled bonded to an oxygen (C=O) in its molecule. This group is also referred to as a carbonyl group. There are several categories of acyl compounds (See Fig 5 below):

1. Aldehydes
2. Ketones
3. Carboxylic Acids
4. Esters

Acyl compounds may undergo reduction with a suitable reducing agent. The reducing agent undergoes oxidation in the process. Aldehydes can be reduced to primary alcohols. Ketones can be reduced to secondary alcohols. Carboxylic acids are reduced to primary alcohols via aldehydes. Esters are reduced to two alcohols, one from the acid fragment of the ester and one from the alcohol fragment. We always use a letter H in brackets when we want to illustrate reduction without specifying the reducing agent.(See Fig 6 below)

There are four reducing agents that will reduce one or more of the acyl compounds as shown in Fig 6 above.

1. Lithium Aluminum Hydride, LiAlH₄ (LAH)
2. Sodium Borohydride, NaBH₄ (NBH)
3. H₂/Cu + CuCr₂O₄ at 5000psi, 175C
4. H₂/Pt

Sodium Borohydride is a less effective, weaker reducing agent which is capable of reducing only the aldehydes and ketones, but it will not touch carboxylic acid or ester functions.

The use of Hydrogen gas in the presence of Cu and Copper II Chromate is called "hydrogenolysis" and is a common way of reducing esters in small scale laboratory reductions. This is also called high pressure Hydrogenation and the Copper and CopperII Chromate serve as Catalysts.

The use of Hydrogen gas in the presence of a Noble metal such as Platinum will also reduce aldehydes, ketones, and carboxylic acids.

An example of how an organic chemist can take advantage of the more discriminating reduction properties of Sodium Borohydride is an example where the reduction of a keto ester is desired. The use of Lithium Aluminum Hydride (LAH) would result in the reduction of both the ester and keto groups in the molecule yielding a diol as the ketone group would be reduced to a hydroxyl group and the ester function would cleave the molecule and reduce the acid portion to a primary alcohol and the alcohol portion of the ester would be reduced to a separate alcohol.

However, if we used Sodium Borohydride (NBH) that reducing agent would only reduce the keto group leaving the ester intact.

On the other hand if we wished to reduce the ester group without touching the keto group we could use hydrogenolysis.

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Organometallic reagents are organic compounds that are bonded to a metal. There are a number of important organometallic reagents but we will discuss two that are important in the synthesis of alcohols.

1. OrganoMagnesium (Grignard), R^-+MgX
2. OrganoLithium, R^-Li⁺
   Preparation of Grignards and OrganoLithiums

   OrganoMagnesium reagents are prepared by reacting an alkyl halide with metallic Magnesium using anhydrous diethyl ether as the solvent.

   R-X + Mg + anhydrous ether ---> R^-+MgX

   It is important that you use anhydrous conditions because of the basicity of the Grignard. They are not only good nucleophiles, but they are excellent bases capable of pulling a Hydrogen ion off of any protic substance such as water or even alcohols.

   R^-+MgX + H₂O ---> R-H + Mg(OH)(X)

   or

   R^-+MgX + R'OH ---> R-H + Mg(OR')(X)

   This can offer a competition with any nucleophilic substitution or addition reaction that was anticipated. The diethyl ether also serves as a stabilizing factor as the oxygen on the diethyl ether will complex with the positive Magnesium in the Grignard.

   It should be noted that Grignards actually react with one another to produce dialkyl magnesiums, R₂Mg. This has been established using radioactive tracing methods, but we will continue to use the Monoalkyl version in this discussion.

   OrganoLithium reagents can be prepared by reacting one mole of alkyl halide for every two moles of metallic Lithium to form the OrganoLithium, R^-Li⁺ and LiX.

   R-X + 2Li + anhydrous diethyl ether ---> R^-Li⁺ + LiX

   OrganoLithiums may be prepared with any alkyl halide but alkyl iodides, R-I, are most reactive and alkyl flourides the least reactive and generally not used in preparing the Organometallic reagent.

   OrganoLithiums react in the same way as Grignards, but they are more reactive and more effective in the synthesis of alcohols. In fact, OrganoLithium reagents must be used immediately upon preparation since long term storage will result in the OrganoLithium reagent reacting with the diethyl ether. Indeed all Organometallic reagents should never be stored on the shelf because of their reactivity with water vapor.

   Preparation of Alcohols Using Organometallic Reagents

   If one reacts a Grignard or OrganoLithium reagent with formaldehyde one can produce a primary alcohol. (See Fig 7 below) Indeed this is the only way to prepare a primary alcohol via an Organometallic reagent.

   Grignards and OrganoLithium reagents react with all other aldehydes to product secondary alcohols.(Fig 7)

   Grignards and OrganoLithium reagents react with ketones to produce tertiary alcohols.(Fig 7)

   

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   Reaction of Organometallic Reagents With Epoxides

   Epoxides are cyclic ethers in which there is two carbons and one oxigen in the ring. Epoxides are highly reactive because of the ring strain that must exist within the ring. This is similar to the cyclopropane reactivity due to ring strain. The carbons in such a three member ring are sp3 hybridized which means that they expect 109.5 degrees bond angles. In a three membered ring the carbons must maintain a 60 degree internal bond angle. If we subtract the angle that the carbons are actually maintaining from the bond angle that they would prefer to maintain, this gives the angle of ring strain. The higher this difference is the more strain the ring is under and the more inclination the ring has to undergo cleavage thereby releasing that ring strain and restoring the carbons to their accustomed 109.5 degree bond angles.

   Grignard Reagents and OrganoLithium reagents will react with Epoxides to form alcohols upon acidification. (See Fig 8 below) This produces alcohols. This reaction suggests a neat sequence of synthetic steps where we might "grow" alcohols to greater complexity (See Fig 8 below)

   

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   R. H. Logan, Instructor of Chemistry, Dallas County Community College District, North Lake College.

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   Acknowledgements:

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   Acknowledgements

   Send Comments to R.H. Logan:

   rhl7460@dcccd.edu

   All textual content copyrighted (c) 1997
   R.H. Logan, Instructor of Chemistry, DCCCD
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   Revised: 7/18/97

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