Minggu, 11 Oktober 2009


Electrophilic Addition Reactions III


We have seen that acid catalysed addition of H2O to an alkene is a 2-step process. The first step, which is rate determining, involves protonation of the double bond. This is followed by addition of a water molecule to the resulting carbocation. The regiochemistry of the first step is determined by the relative stabilities of the two carbocations that may be formed by addition of the proton to either carbon of the double bond. Figure 1 illustrates this idea for the hydration of styrene to produce 1-phenylethanol.

Figure 1

Hydration of Styrene: A Regioselective Reaction

While it is reassuring to know what the regiochemical outcome of a reaction such as the one described in Figure 1 will be, it is problematic if you desire the alternative result, i.e. if you want to prepare 2-phenylethanol, C6H5CH2CH2OH. Given our discussion of the principles which underlie electrophilic addition reactions, you should understand that you cannot prepare 2-phenylethanol by the acid catalysed hydration of styrene. Fortunately there is an alternative methodology available, a 2-step process called hydroboration-oxidation. Figure 2 summarizes the overall transformation using styrene as the reactant.

Figure 2

A Different Way to Skin a Cat

In the first step of the process three moles of the alkene react with one mole of borane, BH3, to produce one mole of trialkylborane, in this case B(CH2CH2C6H5)3. While this material is isolable, it is normally treated directly with an aqueous solution of hydrogen peroxide, HOOH, and sodium hydroxide to produce three moles of the alcohol and a mole of boric acid, NaB(OH)4. We'll see how this happens shortly. First, however, let's look at some experimental data in order to gain a sense of the regioselectivity of the hydroboration-oxidation method. Table 1 lists representative product distributions for this procedure.

Table 1

Product Distributions in Hydroboration-Oxidation

The data in Table 1 reveals several trends. First, as the reaction of 2-methyl-1-butene shows, the regioselectivity of the reaction is highest when one of the doubly bonded carbons is unsubstituted while the other is disubstituted. Second, Alkenes such as 4-methyl-2-pentene, with a single substituent on each carbon of the double bond, give close to 50/50 mixtures of the regioisomeric alcohols.

Before we look at the mechanism of this reaction, let's consider the chemical nature of borane.

Boron Chemistry-Breaking The Rules

During our discussion of the filled shell rules, we looked at experimental evidence which suggested that atoms which have a filled valence shell are more stable than those which don't. In our disucssion of valence bond theory, we saw that stable covalent molecules are formed when atoms share their valence shell electrons in such a way that each atom acquires a filled shell while at the same time remaining electrically neutral. To review a simple example, recall that we "constructed" methane, i.e. created a Lewis structure, by combining one carbon atom, which has 4 electrons in its valence shell, with four hydrogen atoms, each of which has 1 electron in its valence shell. The combination produced a structure in which each atom has a filled shell and a formal charge of zero. A similar approach with boron generates borane, BH3. Unlike methane, borane does not have a filled valence shell. Figure 3 compares these two situations.

Figure 3

Lewis Structures Revisited

Since the boron atom does not have a filled valence shell, borane is electrophilic, i.e. it is a Lewis acid. Like a proton, borane will add to the p bond of an alkene. Figure 4 illustrates the addition of "the elements of" borane, i.e. H and BH2, to one molecule of styrene.

Figure 4

Acid-Base Chemistry in Disguise

The product of the process animated in Figure 4 is an alkylborane. Since the boron atom in this compound is still electron deficient, this alkylborane can react with a second molecule of styrene to form a dialkylborane, which can react with a third molecule of styrene to produce the trialkylborane indicated in Step 1 of Figure 2.

Exercise 1 Draw the structure of the dialkylborane that would be formed by the reaction of borane with two molecules of styrene.

Exercise 2 Suggest a reason why trialkylboranes do not react with a fourth molecule of alkene.

Exercise 3 Draw a Lewis structure for NaB(OH)4. Which atom in this salt has a formal charge of -1?

We have already noted that the hydroboration of alkenes is regioselective; the boron atom adds preferentially to the less substituted carbon of an alkene. This is important because in Step 2 of the hydroboration-oxidation sequence, the boron atom is replaced by an OH group. Figure 5 offers a rationalization of how this transformation occurs for the hydroboration-oxidation of styrene.

Figure 5

The Rest of the Story...

In basic solution the hydrogen peroxide is deprotonated to produce the hydroperoxide anion. This base/nucleophile adds to the boron of the trialkylborane to produce intermediate A. One of the alkyl groups in A rearranges from the boron atom to the adjacent oxygen as indicated by the arrow labeled 1 in Figure 5. As the new C-O bond forms, the OH group leaves (arrow 2), producing intermediate B. This sequence is repeated with two additional hydroperoxide ions to produce intermediate C, a trialkyl boronate ester. Attack of hydroxide ion on the boron atom in C leads to displacement of the conjugate base of 2-phenylethanol. Proton transfer completes the process.

Exercise 4 What is the approximate equilibrium constant for the reaction of hydrogen peroxide with NaOH?

The Stereochemistry of Hydroboration-Oxidation

We have seen that the stereochemical outcome of the electrophilic addition reactions of alkenes depends upon the reaction conditions, and that both syn and anti additions have been observed. Similar studies of the hydroboration-oxidation of cyclic alkenes indicate that the hydroboration step occurs in a syn fashion. Oxidation of the intermediate alkylborane then occurs with retention of configuration. Equation 1 provides a specific example. The net result is syn addition of "the elements of" water to the double bond.

Stereochemical results like these, combined with the fact that these reactions are generally performed in non-polar solvents, suggest that free carbocationic intermediates are not involved in hydroboration. Rather, a concerted process like that shown in Figure 4 has been proposed. But if carbocationic intermediates are not involved, how do we account for the regiochemical preference observed in the addition of BH3 to styrene? Figure 6 suggests a possibility.

Figure 6

Freeze Frame

If, in the transition state of the reaction, there is a slight buildup of charge, then the configuration in the left hand panel of Figure 6 should be more stable than that shown in the right hand panel because the charge may be delocalized into the aromatic ring in the former situation but not in the latter. Regardless of whether Figure 6 accurately reflects the structure of the transition state of this reaction, the key point to remember is that the hydroboration-oxidation sequence provides a means of preparing alcohols that have the opposite regiochemistry of those prepared by acid-catalysed hydration of alkenes.

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