Mechanisms hydroboration-oxidation

The regioselectivity and syn stereochemistry of hydroboration-oxidation coupled with a knowledge of the chemical properties of alkenes and boranes contribute to our under standing of the reaction mechanism... 

Hydroboration-oxidation is a useful method when the desired product is the anti-Mcirkovnikov alcohol. The borane-containing reactant is normally dibo-rane (B2Hg) or the borane tetrahydrofuran complex (BHj THF). No matter what hydroboration agent is used, it s usually simplified to BH3 in the mechanism. BH3 is a useful reactant because it s a good Lewis acid. 

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. 

This process is sometimes abbreviated to S f2 at silicon to save space. The intermediate is a trigonal bipyramid with negatively charged pentacovalent silicon. It is often omitted in drawings because it is formed slowly and decomposes quickly. This mechanism is similar to nucleophilic substitution at boron except that the intermediate is pentacovalent (Si) rather than tetrahedral (B). The hydrolysis of a boron ester at the end of a hydroboration-oxidation sequence would be an example of an analogous boron reaction. 

As was already mentioned, the standard procedure for acid catalyzed alkene hydration exhibits a rather low selectivity. On the other hand, the use of a hydroxymercuration-reduction sequence leads to the exclusive formation of Markovnikov s alcohols. A nearly exclusive anti-Markovnikov s hydration is achieved via a hydroboration-oxidation reaction (see Section 2.4). The result in both these cases is the net addition of H2O, but the basic differences in the reaction mechanisms unambiguously determine a reversed regioselectivity pattern. 

As can be seen in Figure 4, the hydroboration-oxidation of 1-methylcyclopentene produces only the trans-2-methyl-cyclopentanol with a yield of 86%.45 This result implies that the boron atom and the hydrogen atom are added to the double bond simultaneously on a syn mechanism.46 A concerted mechanism is invoked for these additions - it is shown in Figure 5.1... 

Fundamental studies directed toward the elucidation of the mechanism of olefin i.e.f isobutylene, polymerizations yielded a new method for the synthesis of novel linear and tri-arm star telechelic polymers and oligomers [1,2]. The synthesis involves the use of bi- or tri-functional initiator/transfer agents, so called inifers (binifers and trinifers), in conjunction with BCI3 coinitiator and isobutylene, and gives rise to polyisobutylenes carrying exactly two or three terminal -CH2-C(CH3)2Cl groups. These liquid telechelic polyisobutylene chlorides can be readily and quantitatively converted to telechelic polyisobutylene di- or tri-olefins [2,3] which in turn can quantitatively yield by hydroboration/oxidation telechelic polyisobutylene di- and triols [4,5]. 

To understand why the hydroboration-oxidation of propene forms 1-propanol, we must look at the mechanism of the reaction. The boron atom of borane is electron deficient, so borane is the electrophile that reacts with the nucleophilic alkene. As boron accepts the rr electrons and forms a bond with one carbon, it donates a hydride ion to the other carbon. In all the addition reactions that we have seen up to this point, the electrophile adds to the alkene in the first step and the nucleophile adds to the positively charged intermediate in the second step. In contrast, the addition of the electrophilic boron and the nucleophilic hydride ion to the alkene take place in one step. Therefore, an intermediate is not formed. 

R. L. Blankespoor and K. Piers,/. Chem. Educ., 68, 693 (1991), Hydroboration-Oxidation of (lR)-( + )-a-Pinene to Isopinocampheol A Microscale Experiment that Displays Regio-and Stereochemistry Using NMR Spectroscopy and Molecular Mechanics Calculations. 

In designing a multistep synthesis, one must consider aspects of stereochemistry as well as functionality. In the chapters dealing with individual reactions, many examples were given in which the aspects of stereochemistry were a direct consequence of the reaction mechanism. For example, hydroboration-oxidation involves a syn addition followed by oxidation with retention of configuration. The generalization, widely but not universally correct, that reagents attack molecules from the sterically less hindered side was also illustrated on numerous occasions. 

The addition of boron and hydrogen across the carbon-carbon double bond appears to occur by stereospecific syn addition. The replacement of the C—B bond by a C—OH bond in the oxidation step is also stereospecific. The mechanism proposed for the oxidation of one of the carbon-boron bonds is shown in equations 9.47 through 9.51, so the configuration of the carbon-boron bond is retained in the product. As an example, hydroboration-oxidation of 1-methylcyclopentene (50, equation 9.52) followed by oxidation of the organoborane (51) gave only the trans-2-methylcyclohexanol (52). 

In the following sections we shall consider details of the mechanism that lead to the anti-Markovnikov regiochemistry and syn stereochemistry of hydroboration-oxidation. 

Provide explanations based on the mechanism of the hydroboration-oxidation process that would account for why compounds 68-72 are not formed from (H-)-a-pinene. 

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