The hydroboration-oxidation of alkenes

Borane, as a solution in tetrahydrofuran or generated in situ by the reaction of a metal hydride with boron trifluoride etherate, adds readily to alkenes to yield trialkylboranes. With a terminal alkene the reaction is highly (though not completely) regioselective and gives a primary trialkylborane, since the mode of addition results from the electrophilic character of the boron atom. 

These two alkylboranes are important reagents for the hydroboration of other alkenes, since they frequently show in this further reaction a regioselectivity which is greater than that of borane itself. 

The akylboranes may be converted into a vast range of other functionalities64 perhaps the most important is their conversion into alcohols by oxidation with alkaline peroxide. 

The oxidation step is usually carried out in situ and is illustrated by the conversion of hex-l-ene into hexan-l-ol (Expt 5.44) trimethylamine N-oxide has been suggested as a safer alternative oxidising reagent.65 The g.l.c. analysis of the 

An important consequence of the mechanism of this oxidation is that the stereo-isomeric features, resulting from the ds-addition of borane formulated previously (above), are retained in the final product, i.e. the overall reaction is highly stereospecific. Thus reaction of 1-methylcyclohexene with borane followed by oxidation gives frans-2-methylcyclohexan-l-ol.66 

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Thomson v Click Organic Interactive to use a web-based palette to predict products of the hydroboration/oxidation of alkenes. 

The overall reaction is quite complex but involves a rearrangement similar to that described for the hydroboration-oxidation of alkenes (Section 11-6E). The first step is hydroboration of the alkene to a trialkylborane. When the trialkylborane is exposed to carbon monoxide, it reacts (carbonylates) to form a tetracovalent boron, 9 ... 

This section covers the hydroboration-oxidation of alkenes to give alcohols. The author chooses to include this under oxidation since an oxygen atom is introduced into the molecule. This reaction can be performed in a stereocontrolled fashion and it is these methods that are highlighted here. In addition, one similar reductive-oxidation reaction is included, since it is an extremely facile route to benzyl alcohols and a-hydroxyalkanoic acids. 

Hydroboration-oxidation of alkenes (Section 6 11) H and OF add to the double bond with a regioselectivity opposite to that of Markovnikov s rule This is a very good synthetic method addition is syn and no rearrangements are observed... 

Hydroboration-oxidation of alkenes preparation of alcohols Addition of water to alkenes by hydroboration-oxidation gives alcohols via anti-Markovnikov addition. This addition is opposite to the acid-catalysed addition of water. Hydrohoration is regioselective and syn stereospecific. In the addition reaction, borane bonds to the less substituted carbon, and hydrogen to the more substituted carbon of the double bond. For example, propene reacts with borane and THF complex, followed by oxidation with basic hydrogen peroxide (H2O2), to yield propanol. 

The stereochemical result is no longer characterized solely by the fact that the newly formed stereocenters have a uniform configuration relative to each other. This was the only type of stereocontrol possible in the reference reaction 9-BBN + 1-methylcyclohexene (Figure 3.25). In the hydroborations of the cited chiral alkenes with 9-BBN, an additional question arises. What is the relationship between the new stereocenters and the stereocenter(s) already present in the alkene When a uniform relationship between the old and the new stereocenters arises, a type of diastereoselectivity not mentioned previously is present. It is called induced or relative diastereoselectivity. It is based on the fact that the substituents on the stereocenter(s) of the chiral alkene hinder one face of the chiral alkene more than the other. This is an example of what is called substrate control of stereoselectivity. Accordingly, in the hydroborations/oxidations of Figures 3.26 and 3.27, 9-BBN does not add to the top and the bottom sides of the alkenes with the same reaction rate. The transition states of the two modes of addition are not equivalent with respect to energy. The reason for this inequality is that the associated transition states are diastereotopic. They thus have different energies—just diastereomers. 

Hydroboration of alkenes is another example of a stereospecific reaction, in which different stereoisomers of the starting compound react to give different stereoisomers of the product. Problem 8-14 considers the different products formed by the hydroboration-oxidation of two acyclic diastereomers. 

With acyclic asymmetric compounds high levels of diastereoselection are achieved in the hydroboration/oxidation of those alkenes with preexisting allylic stereogenic centers. 

Complexes of cationic rhodium compounds with asymmetric phosphane ligands catalyze the hydroboration of prostereogenic alkenes with catecholborane (see Section D.2.5.2.1.4.). The product alcohols are of 7-96% cc (Table 3). Enantioselectivity is excellent for the hydroboration/oxidation of styrenes but low for stilbenes. The small number of examples studied to date precludes generalizations, however, compared to the uncatalyzed reaction, opposite regioselec-tivity is observed for the addition to styrenes. 

The reported levels of asymmetric induction achieved with this reagent in the hydroboration-oxidation of representative alkenes are in the range of 59-78% ee for cis and 45-75% ee for trisubsti-tuted alkenes. The highest levels of asymmetric induction have been recorded for cw-2-butene (eq 2) and 2-methyl-2-pentene (eq 3). ... 

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. 

Hydroboration-oxidation of alkenes is a method that leads to hydration of the double bond with a regioselectivity opposite to Markovnikov s rule. 

While the four-center transition structure for BH3 addition is a widely used model, other reaction pathways have also been considered. In a synthesis of optically active (-)-l-butanol-l-d, Streitwieser and co-workers used the optically active borane formed from diborane and (-l- )-a-pinene (R2BH) to carry out the hydroboration-oxidation of (Z)-l-butene-l-d. To explain the observed stereochemistry of the reduction, they proposed that hydroboration involves a n complex between R2BH and the alkene (Figure 9.41). Note the close resemblance of such a complex to the cyclic structures... 

The result of hydroboration and subsequent oxidation of an alkene is hydration of the carbon-carbon double bond, here illustrated by the hydroboration-oxidation of 1-hexene to give 1-hexanol. 

By considering the reactions depicted in Schemes 10.3 and 10.4, you can see how the hydroboration-oxidation of an alkene gives an alcohol that is the product of overall anti-Markovnikov addition of the elements of H-OH to the carbon-carbon double bond. Remember, however, that the key step determining the regio-chemistry of the reaction is the Markovnikov addition of the hydrogen-boron bond across the Tr-bond. 

Why is the hydroboration-oxidation of an alkene considered an addition reaction What small molecule has been "added" to the alkene in the overall reaction ... 

Hydroboration-oxidation of alkenes is a valuable laboratory method for the regio-selective and stereoselective hydration of alkenes. Furthermore, this sequence of reactions occurs without rearrangement. 

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