Alkenes alcohols with borane

Strategy What is an immediate precursor of a primary alcohol " Perhaps a terminal alkene, which could be hydrated with non-Markovnikov regiochemistiy by reaction with borane Followed by oxidation with H2O2-... 

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. 

At the beginning of Section 3.4, we wondered whether 3-ethyl-l-methylcyclohexene could also be hydroborated/oxidized/hydrolyzed to furnish the cis, trans-con 11 gured alcohol. There is a solution (Figure 3.32) if two requirements are fulfilled. First, we must rely on the assumption made in Section 3.4.3 that this atkene reacts with the cyclic borane in such a way that the reagent control of stereoselectivity exceeds the substrate control of the stereoselectivity. Second, both the alkene and the borane must be used in enantiomerically pure form. 

Asymmetric hydroboration 2171 of prochiral alkenes with monoisopinocampheyl-borane in the molar ratio of 1 1, followed by a second hydroboration of non-prochiral alkenes with the intermediate dialkylboranes, provides the chiral mixed trialkylbo-ranes. Treatment of these trialkylboranes with acetaldehyde results in the selective, facile elimination of the 3-pinanyl group, providing the corresponding chiral borinic acid esters with high enantiomeric purities. The reaction of these intermediates with base and dichloromethyl methyl ether provides the chiral ketones (Eq. 130)2l8>. A simple synthesis of secondary homoallylic alcohols with excellent enantiomeric purities via B-allyldiisopinocampheylborane has been also reported 219),... 

Pinanyl-9-BBN (Alpine borane 4) is a chiral borane that is readily oxidized by aldehydes. Aliphatic deuterioaldehydes undergo chiral reduction to give alcohols with 84-98% e.e. The chiral alkene is regenerated in the process, only the hydrogen at the 2-position having been utilized, and can be reused. Equation (52) serves as an illustration of the stereochemistry of the process. 

No matter which of the electrophilic methods of double-bond shifting is employed, the thermodynamically most stable alkene is usually formed in the largest amount in most cases, although a few anomalies are known. However, an indirect method of double-bond isomerization us known, leading to migration in the other direction. This involves conversion of the alkene to a borane (15-16), rearrangement of the borane (18-11), oxidation and hydrolysis of the newly formed borane to the alcohol 17 (see 12-31), and dehydration of the alcohol (17-1) to the alkene. The reaction is driven by the fact that with heating the addition of borane is reversible, and the equilibrium favors formation of the less stericaUy hindered borane, which is 16 in this case. 

The reaction of alkenes with borane, monoalkyl and dialkylboranes leads to a new organoborane (see 15-16). Treatment of organoboranes with alkaline H2O2 oxidizes trialkylboranes to esters of boric acid." This reaction does not affect double or triple bonds, aldehydes, ketones, halides, or nitriles that may be present elsewhere in the molecule. There is no rearrangement of the R group itself, and this reaction is a step in the hydroboration method of converting alkenes to alcohols (15-16). The mechanism has been formulated as involving initial formation of an ate complex when the hydroperoxide anion attacks the electrophilic boron... 

The background to this method is provided by the hydroboration of alkenes with diborane, B2H6 (Section 4.8.2). A borane from the very bulky chiral alkene a-pinene (35) is 36, which is of general form R2BH. This borane is monomeric, and is formed by cis addition of diborane to the double bond in each of two a-pinene molecules. In this chiral diborane, the bulk of a-pinene prevents formation of a trialkylborane of type R3B. However, addition of R2BH 36 (Scheme 8.3) to a smaller prochiral alkene occurs preferentially to one face, and is the basis of a synthesis of alcohols with a high degree of enantiomeric purity. 

An atom or a molecule does not have to be positively charged to be an electrophile. Borane (BH3), a neutral molecule, is an electrophile because boron has only six shared electrons in its valence shell. Boron, therefore, readily accepts a pair of electrons in order to complete its octet. Thus, alkenes undergo electrophilic addition reactions with borane serving as the electrophile. When the addition reaction is over, an aqueous solution of sodium hydroxide and hydrogen peroxide is added to the reaction mixture, and the resulting product is an alcohol. The addition of borane to an alkene, followed by reaction with hydroxide ion and hydrogen peroxide, is called hydroboration-oxidation. The overall reaction was first reported by H. C. Brown in 1959. 

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. 

Triphenylsilyl ethers are typically prepared by the reaction of the alcohol with triphenylsilyl chloride (mp 92-94 °C) and imidazole in DMF at room temperature. The dehydrogenative silylation of alcohols can be accomplished with as little as 2 mol% of the commercial Lewis acid tris(pentaf1uorophenyl)borane and a silane such as triphenylsilane or triethylsilane [Scheme 4.98]. Primary, secondary, tertiary and phenolic hydroxyls participate whereas alkenes, alkynes, alkyl halides, nitro compounds, methyl and benzyl ethers, esters and lactones are inert under the conditions. The stability of ether functions depends on the substrate. Thus, tetrahydrofurans appear to be inert whereas epoxides undergo ring cleavage. 1,2- and 1,3-Diols can also be converted to their silylene counterparts as illustrated by the conversion 983 98.4. Hindered silanes such as tri-... 

Draw a structural formula for the alcohol formed by treating each alkene with borane in tetrahydrofuran (THF), followed by hydrogen peroxide in aqueous sodium hydroxide, and specify the stereochemistry where appropriate. (See Example 5.9)... 

Reactions that probe these disconnections are presented in the homework problems. The disconnection diagrams should be read as follows. Alkyl halides are prepared from alkenes, with regioselectivity. Similarly, alcohols are prepared from alkenes with regioselectivity. A chemical reaction involves treatment of an alkene with an acid HX to give the alkyl halide. Another chemical reaction is treatment of an alkene with aqueous acid to give the more substituted alcohol, or with borane and then basic hydrogen peroxide to give the less substituted alcohol. 

Hydroboration of Silylalkenes and SUylalkynes. (Z)-l-Trimethylsily 1-1-alkenes react with DBBS to produce ge/rniime-talloalkanes, which upon oxidation afford alcohols containing the trimethylsilyl group in high yields (72-84%) (eq 13). Unexpectedly, desilylation of (2)-2-(l-trimethylsilyl-l-hexenyl)dibromo-borane is observed during the hydrolysis followed by treatment with 1,3-propanediol. 

A method for converting an alkene to an alcohol. The alkene is treated with borane (BH3) to give a trialkylborane, which is then oxidized with alkaline hydrogen peroxide to give the alcohol. 

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