Peroxides with alkylboranes

This reaction provides a wide variety of products since decomposition of the deuterated alkylborane intermediate (164) can be achieved with hydrogen peroxide to yield labeled alcohols (165), with hydroxylamine-O-sulfonic acid leading to deuterated amines (166), as well as with boiling propionic acid or propionic acid-OD, to form mono- (167) or dideuterio (168) hydrocarbons, respectively. Furthermore, if a monodeuterium label at the sterically more accessible position (170) is sufficient, the use of expensive metal deute-... 

Deuterioboration of 5a-cholest-2-ene (171), followed by oxidation of the alkylborane intermediate with hydrogen peroxide in the presence of sodium hydroxide, illustrates the application of this method for the preparation of c/5-deuterium labeled alcohols.(For the preparation of tra 5 -deuterium labeled alcohols see section VII-A.) The predominant reaction product is 2a-di-5a-cholestan-3a-ol (172, 1.03 D/mole) which is accompanied by 3a-di-5a-cholestan-2a-ol (173) and other minor products." ... 

The alkylborane is then oxidized by the addition of 150 ml of a 15% solution of hydrogen peroxide, while the pH of the reaction mixture is maintained at 7-8 by the simultaneous addition of 3 Asodium hydroxide, the process being carried out at ice-bath temperature. The reaction mixture is neutralized and subjected to steam distillation. The distillate is extracted with ether, and the extract is dried over anhydrous magnesium sulfate. After removal of the ether, distillation yields 18.0 g (70%) of n-octanal, bp 83-85733 mm. 

The second reaction (Equation 11 -3) achieves the synthesis of a primary alcohol by the oxidation of the alkylborane with hydrogen peroxide in basic solution. Starting with a 1-alkene, one can prepare a primary alcohol in two steps ... 

The standard oxidation procedure employs 30% hydrogen peroxide and 3 M sodium hydroxide. However, functionalities sensitive to strong alkali require milder conditions. In such cases, buffering, simultaneous addition of base and peroxide,492 or oxidation with Oxone ,493 triethylamine A-oxide,494-498 peracids,499,500 or sodium hypochlorite50 were recommended. Oxygen has been rarely used for such purpose,502 but trialkylboranes in bromoperfluorooctane were cleanly reacted with oxygen with the retention of configuration of the secondary alkylboranes (Equation (104)).503... 

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. 

When the anions 287 derived from compounds 285 were allowed to react with tri-alkylboranes, followed by oxidation, the expected ketones were obtained455. A similar process is described in Scheme 40 for bis(phenylsulfanyl)alkyllithiums151,152. Successive treatment of the obtained trialkylborane adducts 288 with mercury(II) chloride and hydrogen peroxide yielded tertiary alcohols (Scheme 75)456. The last reactions failed with bis(phenylsulfanyl)alkyllithiums. 

Reaction of the two neutral alkylborane adducts with hydrogen peroxide gives two alcohol isomers. In one isomer, the two methyl groups have a cis relationship, and in the other isomer they have a trans relationship. 

An attempt to distinguish the two by lsO labeling was frustrated by exchange in the perrhenate product. However, the authors favored the latter mechanism, based on the observation that the observed rate constants suggested that kA or /cMto had to be near the diffusion-controlled limit, coupled with the known higher nucleophilicity of the hydroperoxide vs hydroxide anions.37 The formation of the new C—O bond in this case is thus reminiscent of the oxidation of alkylboranes with hydrogen peroxide.38... 

Oxidation of alkenylboranes with alkaline hydrogen peroxide is an important pathway to aldehydes and ketones (equation 13). Care must be taken to inhibit hydrolysis of the alkenylborane to the corresponding alkene and hence buffered conditions are frequently us. The reaction toloates the same wide range of functionality as the oxidation of alkylboranes. 

Reaction is carried out in an ether, commonly tetrahydrofuran or diglyme //ethylene glycoX w thyl ether, CH3OCH2CH2OCH2CH2OCH3). Diborane is commercially available in tetrahydrofuran solution. The alkylboranes are not isolated, but are simply treated in situ with alkaline hydrogen peroxide. 

When hydroboration of an olefin is carried out with the intention of oxidizing an initially formed secondary alcohol to a ketone, hydrogen peroxide oxidation can be dispensed with and the alkylborane oxidized directly with chromic acid. Thus Pappo converted a hydroxyl-free A -steroid into a mixture of stereoisomeric alkyl-boranes comparable to (1) and (2), oxidized the mixture with chromic acid, and obtained the 6-keto-5a-steroid in good yield the initially formed 6-keto-5i3-steroid underwent isomerism in the process. H. C. Brown developed an efficient two-phase system for oxidation of either alkylboranes or free alcohols to the ketones using aqueous chromic acid and ether. 

Cleavage of cyclopropanes. In the absence of a solvent, cyclopropanes are reductively cleaved by diborane. Thus norcarane heated with diborane at 100 for 1-2 hrs. gives the alkylborane (2), identified by peroxide cleavage to cyclohexyl-methanol (3). No reaction occurred in tetrahydrofurane. 

Although water, in some cases, has undergone addition across the C-C double bond in a vinylcyclopropane under acidic, - neutral, " and basic " - aqueous conditions, e.g. formation of 2, the reaction has more often been performed using a two-step procedure. Most frequently used was a one-pot synthesis consisting of hydroboration followed by oxidation with hydrogen peroxide/sodium hydroxide. The alkylboranes, formed in the first step, can be isolated. - The first step has generally been carried out using diborane in tetrahydrofuran 398,410,430,745,852,1025,1590,1609,1793,1833.1877-1884 9-borabi-... 

When the alkylborane is oxidized by reaction with hydrogen peroxide and hydroxide ion, the OH group ends up in the same position as the boron group it replaces. Consequently, the overall hydroboration-oxidation reaction amounts to a syn addition of water to a carbon-carbon double bond. 

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. 

You might recall a somewhat related mechanistic rearrangement, the migration of a group from boron to oxygen during the oxidation of alkylboranes with basic hydrogen peroxide. 

Hydroboration-Oxidation An alkene reacts with BHsTHF or diborane to produce an alkylborane. Oxidation and hydrolysis of the alkylborane with hydrogen peroxide and base yield an alcohol (Section 8.6). 

Hexene reacts with borane to give a new product known as an alkylborane, which is listed as unknown for the moment. The alkylborane product is treated with NaOH and H2O2 in a second chemical reaction and the major product obtained after this two-reaction process (two-step process) is 1-hexanol (52), isolated in 81% yield. The second reaction with hydroxide and peroxide will be discussed later in this section, but for now focus attention on the new borane product of the first reaction. The remainder of the 100% is alcohol 53 as a minor product, and this will be explained later. 

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