Alkylboranes

Isomerization of Alkylboranes. One of the early discoveries of organoboranes was their tendency to undergo isomerization if the temperature approached 160°C. This isomerization involves migration of the boron from a more to a less substituted position, usually giving the terminal alkylborane as the predom- 

This process is synthetically important because a sacrificial alkene such as 1-decene or 1-hexadecene can be added to bias the overall reaction toward a specific target alkene. Mechanistically, thermal isomerization apparently involves a series of reversible elimination reactions of borane followed by re-addition in an anti-Markovnikov manner.2 If the sacrificial alkene has a significantly higher boiling point, then the desired alkene can he distilled from the reaction medium.22a xhe sacrificial alkene must not boil 160°C, however, which is the temperature required for borane isomerization. This process makes it possible to isomerize the double bond of an alkene to a less substituted isomer, a process that Brown termed contrathermodynamic isomerization.29,30 methylenecyclohexane (41) was prepared from 1-methylcyclohexene by 

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With sodium hydroxide as the base boron of the alkylborane is converted to the water soluble and easily removed sodium salt of boric acid... 

Common catalyst compositions contain oxides or ionic forms of platinum, nickel, copper, cobalt, or palladium which are often present as mixtures of more than one metal. Metal hydrides, such as lithium aluminum hydride [16853-85-3] or sodium borohydride [16940-66-2] can also be used to reduce aldehydes. Depending on additional functionahties that may be present in the aldehyde molecule, specialized reducing reagents such as trimethoxyalurninum hydride or alkylboranes (less reactive and more selective) may be used. Other less industrially significant reduction procedures such as the Clemmensen reduction or the modified Wolff-Kishner reduction exist as well. 

Alkylfluoroboranes result from the reaction of the appropriate alkylborane and BF under suitable conditions (37) ... 

Mono- and dialkylboranes usually exist as bridged dimers, yy -dialkyldiboranes and yy -tetraalkyldiboranes. Only very hindered alkylboranes, eg, bis(2,3-dimethyl-2-butyl) borane (39), are monomeric. However, for convenience of presentation monomers are shown in the equations. 

Usually, organoboranes are sensitive to oxygen. Simple trialkylboranes are spontaneously flammable in contact with air. Nevertheless, under carefully controlled conditions the reaction of organoboranes with oxygen can be used for the preparation of alcohols or alkyl hydroperoxides (228,229). Aldehydes are produced by oxidation of primary alkylboranes with pyridinium chi orochrom ate (188). Chromic acid at pH < 3 transforms secondary alkyl and cycloalkylboranes into ketones pyridinium chi orochrom ate can also be used (230,231). A convenient procedure for the direct conversion of terminal alkenes into carboxyUc acids employs hydroboration with dibromoborane—dimethyl sulfide and oxidation of the intermediate alkyldibromoborane with chromium trioxide in 90% aqueous acetic acid (232,233). 

Mercuration. Mercury(II) salts react with alkyl-, alkenyl-, and arylboranes to yield organomercurials, which are usehil synthetic intermediates (263). For example, dialkyhnercury and alkyhnercury acetates can be prepared from primary trialkylboranes by treatment with mercury(II) chloride in the presence of sodium hydroxide or with mercury(II) acetate in tetrahydrofuran (3,264). Mercuration of 3 -alkylboranes is sluggish and requires prolonged heating. Alkenyl groups are transferred from boron to mercury with retention of configuration (243,265). 

Carbanioas derived from the other above mentioned methane derivatives react with alkylboranes, bornic, and boronic esters, providing rich possibihties for the preparation of siagle-carbon iasertion products. Thus 2-aLkyl-l,3,2-dithiaborolanes are converted iato acids or thioacetals by trichloromethyllithium (335). 

Reactions with Acyl Garbanion Equivalents. Alkyl substituted carbanions CRXY with potential leaving groups X, Y, and acyl carbanion equivalents or CHRX (342) react with alkylboranes, providing products with mixed alkyl groups derived from both reagents. 

OC-All lation of Carbonyl Compounds and Derivatives. The organoborate iatermediates generated by the reaction of alkylboranes with carbanions derived from a-halocarbonyl compounds and a-halonitriles rearrange to give a-alkylated products. 

A noteworthy development is the use of KH for complexing alkylboranes and alkoxyboranes to form various boron hydrides used as reducing agents in the pharmaceutical industry. Potassium tri-j -butylborohydride [54575-50-7] KB(CH(CH2)C2H )2H, and potassium trisiamylborohydride [67966-25-0] KB(CH(CH2)CH(CH2)2)3H, are usefiil for the stereoselective reduction of ketones (66) and for the conjugate reduction and alkylation of a,P-unsaturated ketones (67). 

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-... 

The hydroboration step, being very sensitive to steric effects, yields only secondary alkylboranes from trisubstituted double bonds, whereas the less hindered alkylborane is formed predominantly from disubstituted steroidal double bonds. The diborane attack occurs usually towards the a-side and hence results in overall a-hydration of double bonds after alkaline hydrogen peroxide oxidation. ... 

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 successful labeling of the elusive 14a-position in cholestane represents a very important application of this reaction.It is known that hydroboration of the double bond in 5of-cholest-14-ene (174) occurs on the a-side. Consequently, by using deuteriodiborane (generated by the reaction of boron trifluoride etherate with lithium aluminum deuteride) and then propionic acid for hydrolysis of the alkylborane intermediate, 14a-d,-5a-cholestane (175) is obtained in 90% isotopic purity. This method also provides a facile route to the C-15 labeled analog (176) when the alkylborane derived from 5a-cholest-14-ene is hydrolyzed with propionic acid-OD. ... 

In the next step, one of the borane-hydrogens is transferred to a sp -carbon center of the alkene and a carbon-boron bond is formed, via a four-membered cyclic transition state 6. A mono-alkyIborane R-BH2 molecule thus formed can react the same way with two other alkene molecules, to yield a trialkylborane R3B. In case of tri- and tctra-substituted alkenes—e.g. 2-methylbut-2-ene 7 and 2,3-dimethylbut-2-ene 9—which lead to sterically demanding alkyl-substituents at the boron center, borane will react with only two or even only one equivalent of alkene, to yield a alkylborane or mono alky Iborane respectively ... 

The hydroboration is a regioselective reaction. In general the addition will lead to a product, where the boron is connected to the less substituted or less sterically hindered carbon center. If the olefinic carbons do not differ much in reactivity or their sterical environment, the regioselectivity may be low. It can be enhanced by use of a less reactive alkylborane—e.g. disiamylborane 8 ... 

The alkylboranes obtained by the hydroboration reaction are versatile intermediates for further transformations. The most important transformation is the oxidation to yield alcohols 17 it is usually carried out by treatment with hydroperoxide in alkaline solution. The group R migrates from boron to oxygen with retention of configuration ... 

The alkylborane is oxidized by the addition of 32 ml of 3 A sodium hydroxide followed by 32 ml of 30% hydrogen peroxide to the stirred solution maintained at 30-50° (water bath), and the stirring is continued at the temperature for 1 hour. 

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. 

Hydrolioration (Section 7.5) Addition of borane (BH i) or an alkylborane to an alkene. The resultant trialkyliiorane products are useful synthetic intermediates that can be oxidized to yield alcohols. 

Enantiomerically pure alkylboranes arc known to be excellent reagents for asymmetric reduction but they can also be used to generate enantiomerically pure /V-borylimines by partial reduction of nitriles. Addition of organolithium and Grignard reagents to these compounds affords secondary carbinamines in moderate to good yield but low enantioselectivity13,14. The best results reported so far are shown below. 

Alkylboranes can be coupled by treatment with silver nitrate and base." Since alkylboranes are easily prepared from alkenes (15-16), this is essentially a way of coupling and reducing alkenes in fact, alkenes can be hydroborated and coupled in the same flask. For symmetrical coupling (R = R ) yields range from 60 to 80% for terminal alkenes and from 35 to 50% for internal ones. Unsymmetrical coupling has also been carried out, but with lower yields. Arylboranes react similarly, yielding biaryls. The mechanism is probably of the free-radical type. 

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