Peroxides hydrogen peroxide reaction with boranes

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. 

In addition to the oxymercuration method, which yields the Markovnikov product, a complementary method that yields the non-Markovnikov product is also useful. Discovered in 1959 by H. C. Brown and cailed hydroboration, the reaction involves addition of a B-H bond of borane, BH3, to an alkene to yield an organoborane intermediate, RBH2. Oxidation of the organoborane by reaction with basic hydrogen peroxide, H2O2, then gives an alcohol. For example ... 

As mentioned in Sect. 2.2, phosphine oxides are air-stable compounds, making their use in the field of asymmetric catalysis convenient. Moreover, they present electronic properties very different from the corresponding free phosphines and thus may be employed in different types of enantioselective reactions, m-Chloroperbenzoic acid (m-CPBA) has been showed to be a powerful reagent for the stereospecific oxidation of enantiomerically pure P-chirogenic phos-phine-boranes [98], affording R,R)-97 from Ad-BisP 6 (Scheme 18) [99]. The synthesis of R,R)-98 and (S,S)-99, which possess a f-Bu substituent, differs from the precedent in that deboranation precedes oxidation with hydrogen peroxide to yield the corresponding enantiomerically pure diphosphine oxides (Scheme 18) [99]. 

The addition of allylic boron reagents to carbonyl compounds first leads to homoallylic alcohol derivatives 36 or 37 that contain a covalent B-O bond (Eqs. 46 and 47). These adducts must be cleaved at the end of the reaction to isolate the free alcohol product from the reaction mixture. To cleave the covalent B-0 bond in these intermediates, a hydrolytic or oxidative work-up is required. For additions of allylic boranes, an oxidative work-up of the borinic ester intermediate 36 (R = alkyl) with basic hydrogen peroxide is preferred. For additions of allylic boronate derivatives, a simpler hydrolysis (acidic or basic) or triethanolamine exchange is generally performed as a means to cleave the borate intermediate 37 (Y = O-alkyl). The facility with which the borate ester is hydrolyzed depends primarily on the size of the substituents, but this operation is usually straightforward. For sensitive carbonyl substrates, the choice of allylic derivative, borane or boronate, may thus be dictated by the particular work-up conditions required. 

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. 

Hydroboration-oxidation of alkynes preparation of aldehydes and ketones Hydroboration-oxidation of terminal alkynes gives syn addition of water across the triple bond. The reaction is regioselective and follows anti-Markovnikov addition. Terminal alkynes are converted to aldehydes, and all other alkynes are converted to ketones. A sterically hindered dialkylborane must be used to prevent the addition of two borane molecules. A vinyl borane is produced with anU-Markovnikov orientation, which is oxidized by basic hydrogen peroxide to an enol. This enol tautomerizes readily to the more stable keto form. 

C. 1-Hexanol. To a solution of trihexylborane in a 500-ml. three-necked flask [prepared from 25.3 g. (0.30 mole) of 1-hexene in 150 ml. of tetrahydrofuran and 84 ml. of a 1.20ilf solution of borane in tetrahydrofuran, as described in Section A] is added 34 ml. (0.10 mole) of a 3N solution of sodium hydroxide. This is followed by the dropwise addition of 36 ml. (0.35 mole) of 30% hydrogen peroxide solution at a rate such that the reaction temperature is maintained at approximately 35° (water bath). After being stirred at room temperature for one hour, the mixture is poured into 100 ml. of water. The organic phase is separated and the aqueous phase is extracted with 50 ml. of ether. The combined organic extracts are washed with three 50-ml. portions of saturated brine solution and dried over Drierite. After the bulk of the solvent is removed by distillation, the residue is fractionated with a 24-in. Teflon spinning band column (Note 10) to provide 7.7-8.2 g. (25.1-26.7%) of 1-hexanol of 95% purity, b.p. 145-153° and 10.1-15.4 g. (33.3-50.3%) of pure 1-hexanol, b.p. 153-155° (Note 11). The total yield of material with >95% purity is 58.4-77%. 

A solution of the borane (1 mmol) in THF (3 ml) was treated with the ylide (374 mg, 1 mmol) under argon, at room temperature. After stirring for 3 h, 3n aqueous sodium hydroxide (2 ml) and 30% hydrogen peroxide (1 ml) were added to the reaction mixture, which was allowed to stand overnight it was then neutralized with 1 N HC1 (7 ml), extracted with dichloromethane (3x15 ml) and dried. Concentration and purification by preparative TLC (petroleum ether-ether) yielded 5-tosylamino-cyclooctanol (266 mg, 91%) m.p. 88-89°C. 

Another method for the addition of the elements of water, H and OH, to an alkene was developed by H. C. Brown, who shared the 1979 Nobel Prize in chemistry for this work. In this reaction the alkene is first allowed to react with a complex of borane (BH3) in tetrahydrofuran (THF). The initial product is then allowed to react with a basic solution of hydrogen peroxide. An example is shown in the following equation ... 

The dialkenylchloroboranes undergo the usual reactions of vinylic boranes, e.g., protonolysis with acetic acid gives olefins, oxidation with alkaline hydrogen peroxide provides the corresponding carbonyl compounds. However, the most useful reactions of these compounds are their ready conversion to the stereochemically pure (E, Z)-1,3-dienes by the Zweifel reaction with I2-NaOH 37>107.108> and into the symmetrical (E,E)- 1,3-dienes, 09 0), mono-olefins 1U) and 1,4-dienes (Chart 10). 

The BH3 THF reagent is the form of borane commonly used in organic reactions. BH3 adds to the double bond of an alkene to give an alkylborane. Basic hydrogen peroxide oxidizes the alkylborane to an alcohol. In effect, hydroboration-oxidation converts alkenes to alcohols by adding water across the double bond, with anti-Markovnikov orientation. 

Alkaline hydrogen peroxide easily oxidizes practically all alkyl- and cycloalkyl-boranes in a rapid and quantitative fashion. There is a reactivity trend of R3B > R2BX > RBX2 (X = halogen, OH, OR note that boron halides will anyway be hydrolyzed to hydroxides under the oxidation conditions), which is consistent with reduced acceptor ability of the boron atom when an electron pair of an adjacent group interacts with the vacant boron oibital. Increasing die steric hindrance around the boron atom may inhibit the reaction to the point at which it ceases altogether. - ... 

The synthetic value of the reaction lies in the modification of these organoboranes. The commonest reaction involves the decomposition of the borane by alkaline hydrogen peroxide. The highly nucleophilic hydroperoxide anion attacks the electron-deficient boron with the formation of an ate complex. Rearrangement of this leads to the formation of a borate ester which then undergoes hydrolysis to an alcohol in which an oxygen atom has replaced the boron (Scheme 3.15). The overall outcome of this reaction is the anti-Markownikoff hydration of the double bond. The regiochemistry is the reverse of the acid-catalysed hydration of an alkene. The overall addition of water takes place in a cis manner on the less-hindered face of the double bond. 

The reduction is bimolecular and thus the rate is dependent on concentration. Running the reaction neat provides the fastest rates. Usually an excess of Alpine-Borane is used to insure that the reaction does not become excessively slow at the end of the reduction. The excess organoborane may be destroyed by addition of an aldehyde such as Acetaldehyde. The resulting alkoxy-9-BBN may be treated with Ethanolamine to liberate the alcohol and precipitate the majority of the 9-BBN. Any remaining borane impurities may be removed by oxidation with basic Hydrogen Peroxide. 

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