Hydroboration, alkene regiochemistry

One of the features that makes the hydrobora ( ion reaction so useful is the regiochemistry that results when an unsymmetrical alkene is hydroborated. For example, hydroboration/oxidation of 1-methylcyclopentene yields trans-2-methylcydopentanol. Boron and hydrogen both add to the alkene from the same face of the double bond—that is, with syn stereochemistry, the opposite of anti—with boron attaching to the less highly substituted carbon. During the oxidation step, the boron is replaced by an -OH with the same stereochemistry, resulting in an overall syn non-Markovnikov addition of water. This stereochemical result is particularly useful because it is complementary to the Markovnikov regiochemistry observed for oxymercuration. 

The chemistry of alkynes is dominated by electrophilic addition reactions, similar to those of alkenes. Alkynes react with HBr and HC1 to yield vinylic halides and with Br2 and Cl2 to yield 1,2-dihalides (vicinal dihalides). Alkynes can be hydrated by reaction with aqueous sulfuric acid in the presence of mercury(ll) catalyst. The reaction leads to an intermediate enol that immediately isomerizes to yield a ketone tautomer. Since the addition reaction occurs with Markovnikov regiochemistry, a methyl ketone is produced from a terminal alkyne. Alternatively, hydroboration/oxidation of a terminal alkyne yields an aldehyde. 

Hydroboration-oxidation leads to stereospecific syn addition of H and OH across a carbon-carbon double bond. The regiochemistry of addition is opposite to that predicted by Markovnikov s rule. Hydroboration-oxidation of the E alkene gives alcohol A. 

Asymmetric hydroboration followed by oxidation is used to give optically active alcohols. For example, addition of (+)-IpcBH2 to 1-phenylcyclopentene followed by oxidation gives S,2R)-trans-2-phenylcyclopentanol in 100% e.e. (Equation B2.9). The structure of the product alcohol reveals that the homochiral hydroborating reagent encounters fewer unfavourable steric interactions with alkene substituents if it approaches the lower face of the alkene as drawn in Equation B2.9. This preference determines the absolute stereochemistry of the product. (The regiochemistry and relative stereochemistry of the product are determined by fundamental hydroboration characteristics.)... 

The overall result of the hydroboration-oxidation sequence is addition of water to an alkene with the opposite regiochemistry to that expected for a conventional acid-catalysed hydration. The usual way to do such a hydration is by oxymercuration-reduction. 

NMR can be used to help identify the product of nearly every reaction run in the laboratory. For example, we said in Section 7.5 that hydroboration/oxidation ol alkenes occurs with non-Vlarkovnikov regiochemistry to yield the less highly substituted alcohol. With the help of NMR, we can now prove this statement. 

Why does alkene hydroboration take place with non-Markovnikov regiochemistry, yielding the less highly substituted alcohol Hydroboration differs from many other alkene addition reactions in that it occurs in a single step without a carbocation intermediate. We can view the reaction as taking place through a four-center, cyclic transition state, as shown in Figure 7.6 p. 244). Since both C-H and C-B bonds form at the same time and from the same face of the alkene, syn stereochemistry is observed. 

In addition to electronic factors, a steric factor is probably also involved in determining the regiochemistry of hydroboration. Attachment of boron is favored at the less sterically hindered carbon atom of the alkene, rather than at the more hindered carbon, because there is less steric crowding in the resultant transition state ... 

The hydroboration reaction with alkenes to produce alkylboranes (sec. 5.2) proceeds by a four-center transition state rather than a cationic intermediate. The regiochemistry of the final alkylborane product is controlled by the nonbonded steric interactions of the groups attached to boron (in this case sec-isoamyl from the disiamylborane) and the groups on the alkene. Oxidation with basic hydrogen peroxide converts the borane to the anti-Markovnikov alcohol (2). The difference in regiochemistry between 1 and 2 arose because the mechanism for generating each relied on difference factors. 

The observation of consistent syn addition in the hydroboration step suggests that the mechanism for addition of BH3 is different from all of the addition mechanisms discussed so far except one. As discussed on page 580, a one-step, four-center mechanism was considered in the s)m addition of F2 to an alkene, and a similar mechanism can explain the stereochemistry of BH3 addition. Moreover, the regiochemistry of addition to imsymmetrical alkenes can be rationalized in terms of the steric and electronic effects present in such a transition structure. 

The examples in Equation 16.45 show that the regiochemistry of the metal-catalyzed hydroboration of alkenes contrasts with that of tlie metal-catalyzed hydroboration of vinylarenes. The predominant products from the metal-catalyzed hydroborations of 1-alkenes are terminal boranes. - " These terminal boranes can also be formed from internal alkenes, as shown in Equation 16.46. Similar to hydrosilylation witli Speier s catalyst, the... 

Alcohols can be prepared from a variety of other functional groups, including by reduction of a carbonyl, hydration of an alkene, or substitution of a leaving group. Remember, regiochemistry is a concern when starting with an alkene, and water can be added with either Markovnikov (oxymercuration-demercuration) or anti-Markovnikov (hydroboration-oxidation) orientation. 

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