Regiochemistry hydroboration

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. 

What product will result from hydroboration/oxidation of 7-methylcyclo-pentene with deuterated borane, BD3 Show both the stereochemistry (spatial arrangement) and the regiochemistry (orientation) of the product. 

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. 

Do not confuse the concepts of regiochemistry and stereochemistry. For instance, in addition reactions, the term anti-Markovnikov addition refers to the re-giochemistty of the addition, but the term anti refers to the stereochemistry of the addition. Smdents often confuse these concepts (probably because both terms have the word antF). It is possible for an addition reaction to be anti-Markovnikov and a syn addition (hydroboration is an example that you will learn about at some point in time). You must realize that regiochemistry and stereochemistry are two totally different concepts. 

The stereochemical outcome is replacement of the C—B bond by a C—O bond with retention of configuration. In combination with stereospecific syn hydroboration, this allows the structure and stereochemistry of the alcohols to be predicted with confidence. The preference for hydroboration at the least-substituted carbon of a double bond results in the alcohol being formed with regiochemistry that is complementary to that observed by direct hydration or oxymercuration, that is, anti-Markovnikov. 

Hydroboration of allylsilanes 1,2- or 1,3-diols.1 A dimethylphenylsilyl group can markedly affect the regiochemistry of hydroboration of an adjacent double... 

As expected, allylic alcohols and ethers afford v/c-diol derivatives upon hydroboration. However, in the presence of Wilkinson s catalyst, a reverse regiochemistry for the hydroboration is observed [108]. There is the possibility that boron, rather than hydrogen, is transferred from the metal to the olefin. In other words, the boron acts as a donor. 

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.)... 

As is generally the case with Rh-catalyzed hydroborations, genuinely successful enantioselective reaction (> 90 % ee) has been recorded only for vinylarenes. Since the normal regiochemistry of these reactions places the rhodium at the benzylic position, some favorable interaction with the ring is to be expected the the reactive rhodium benzyl intermediate this may formally be represented as an -complex, for which literature precedents exist [104] (Scheme 33). 

Although the hydroboration-oxidation reaction gives a product with a regiochemistry opposite to that predicted by Markovnikov s rule, the regiochemistry is in accord with the mechanistic version of this rule—that is, the electrophile adds to the less substituted carbon. Let s look at the mechanism of this reaction. 

Table 11.4 summarizes the reactions in which the electrophile and the nucleophile are linked in the same molecule (hydroboration, hydroxylation, ozonolysis). These additions occur in a concerted manner. The regiochemistry of the addition is such that the nucleophile attaches to the carbon that would be more stable as a carbocation and the addition occurs with syn stereochemistry. 

The hydroboration-oxidation of a-pinene gives the product shown. Carefully explain the regiochemistry and the stereochemistry of this reaction. 

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. 

The nitrogen atom in A3-piperideines would be expected to influence the addition of unsymmetrical reagents to the double bond. Although this effect has not been extensively studied, the results on the hydroboration-oxidation of a number of N- substituted A3-piperideines show a preference for the piperidin-3-ol (Scheme 16) (70JOC802). Initial coordination of borane with the nitrogen atom was proposed and the observed regiochemistry is believed to be the result of electronic factors (70TL1133). 

Strategy Hydroboration/oxidation occurs with non-Markovnikov regiochemistry to give products in which -OH is bonded to the less highly substituted carbon. 

A second metal-catalyzed route to alpha-thioboronate esters consists of the regiospecific, Markovnikov hydroboration of phenyl vinylsulfide which proceeds in high yield to give 14a,b (Equation 11). We are in the process of extending this unique reaction to other alkenyl sulfides and to alkenyl phosphines in order to determin whether the observed regiochemistry of addition is due to a directing effect of the soft heteroatom donor towards the catalyst center. 

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 ... 

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