Disiamylborane1

[1069-54-1]  · C10H23B  · Disiamylborane  · (MW 154.14)

(hindered organoborane for chemo-2 and regioselective3 hydroboration and chemo-4 and stereoselective5 reduction; can be used to mediate couplings of alkenes6 and alkynes7)

Alternate Name: bis(1,2-dimethylpropyl)borane.

Physical Data: mp 35-40 °C; fp -17 °C.

Solubility: sol THF, ether, diglyme.

Form Supplied in: prepared in situ; kits are available.

Preparative Methods: generally prepared by reaction of Diborane with 2-methyl-2-butene in ethereal solvents at 0 °C;8 alternatively by substituting borane-1,4-thioxane.9

Handling, Storage, and Precautions: flammable; very air- and moisture-sensitive. Generally prepared immediately prior to use. Handle in a fume hood.

Hydroboration of Alkenes.

Compounds containing double bonds react with disiamylborane (Sia2BH) to give tertiary boranes of the form Sia2BR (eq 1). These trialkylboranes are generally not isolated, but are submitted to further reactions to provide a variety of products. The reactions of disiamylborane adducts are typical of organoboranes. If the intermediate is quenched with acid, the borane is replaced with a proton (eq 2); the net result is a syn hydrogenation.10

The organoborane may also be oxidized with alkaline peroxide to give an alcohol which retains the position and configuration of the borane adduct. Thus, for example, Sia2BH is the reagent of choice for anti-Markovnikov hydration of o-unsaturated esters due to its high selectivity for terminal hydroboration (eq 3).11 Alternatively, direct oxidation of the intermediate resulting from hydroboration of a terminal alkene with Pyridinium Chlorochromate provides the aldehyde (eq 4).12 Once again, Sia2BH is the reagent of choice for this reaction because of its high selectivity for the alkenic terminus. Reaction of Sia2BR with Iodine under basic conditions provides the corresponding iodide.13 When R is primary, the formation of RI proceeds in high yield, because transfer of the siamyl groups occurs only slowly (eqs 5 and 6). A similar transformation may be accomplished using borane, but yields are generally lower because R3B gives only partial conversion to RI.14 This Sia2BH-based approach was found to be clearly superior to a hydrozirconation route for the iodination of the (h6-hexabutenylbenzene)(h5-cyclopentadienyl)iron cationic complex illustrated in eq 7.15

Unlike diborane, disiamylborane exists as a dimer even in solution in THF.16 This failure to dissociate in a coordinating solvent, presumably due to the steric bulk of the siamyl groups which disfavor the borane/ether complex, causes Sia2BH to act as a highly hindered hydroborating agent. As a general rule, Sia2BH reacts preferentially with less sterically hindered alkenes. An extensive comparative study has determined the relative rates of reaction of double bonds with a variety of substitution patterns.17

Reaction occurs to place the borane at the least encumbered position. These differences in reaction rate are often large enough to be synthetically useful; thus 1-hexene reacts at the terminal position with >99:1 selectivity (with diborane the selectivity for the 1-position is ~15:1).18 Sia2BH even responds to the bulk of the substituents on the double bond; 4-methyl-trans-2-pentene reacts slowly with the reagent (12 h at 0 °C) to give mainly the 2-alcohol (Scheme 1).18

This high level of steric discrimination makes Sia2BH a useful reagent for selective reaction with one double bond of a polyunsaturated compound; for example, hydroboration of limonene (eq 8) gives (after oxidative workup) a good yield of a-terpineol,19 while the diene of eq 9 reacts selectively at one of the four possible alkenic positions.20

Sia2BH-mediated hydroboration is a key step in a unique carbocyclization reaction (eq 10).6 Thus dienyl iodide is selectively hydroborated at the less-substituted alkene; oxidative cyclization of this intermediate provides a cycloalkene. The borane route provides a useful alternative to methods involving palladium catalysis.

Hydroboration of Alkynes.

Sia2BH is a valuable reagent for the chemo- and regioselective hydroboration of alkynes. The reagent is more selective for terminal hydroboration than diborane; it is also more selective for monoaddition.8 Reaction of 1-hexyne with Sia2BH gives a vinylborane as an intermediate. Hydrolysis gives 1-hexene as the product (eq 11). In the case of internal alkynes, this process results in a net syn hydrogenation to give a (Z)-alkene (eq 14).21 Oxidative workup of the vinylborane provides an aldehyde (eq 12).8 The intermediate can also be oxidized with copper salts in the presence of cyanide ion to give an a,b-unsaturated nitrile (eq 13).22 Sia2BH is superior to Dicyclohexylborane for this transformation, which provides an alternative to the hydroalumination/cyanogen sequence.23

The reaction of Sia2BH with 1,4-dichloro-2-butyne, followed by treatment of the intermediate with a thiolate anion, provides a one-pot synthesis of 2-thioalkylbutadienes (eq 15).24 A similar strategy, replacing the thiolate with an organolithium reagent, is unsuccessful for the synthesis of 2-alkylbutadienes, as the siamyl group migrates preferentially to primary alkyl.25

Sia2BH adds regioselectively to a variety of asymmetrically substituted alkynes. Reaction with alkynyl sulfides occurs primarily a to sulfur; processing of the vinylborane intermediate by hydrolysis (of the corresponding ate complex) or oxidation leads to a vinyl sulfide (eq 17) or thiolester (eq 16), respectively.26 Cyclohexylborane is more selective (83:17) for a-boration than Sia2BH (72:28) in this reaction. The reagent also reacts selectively at the 2-position of 1-chloro-2-heptyne; acid hydrolysis leads to a (Z)-allyl chloride (eq 18), while base treatment gives the terminal allene (eq 19).27 Similarly, alkynyl acetals react with Sia2BH to place the borane proximal to the heteroatom.28

Hydroboration of alkynes with Sia2BH is more rapid than the corresponding reaction of alkenes, allowing for the selective conversion of enynes into dienes (eq 21)2 or enones (eq 20).29

The enynes themselves can be prepared in Sia2BH-mediated reactions. Hydroboration of diynes protected by bulky silyl groups occurs in a highly regioselective fashion; hydrolysis of the resultant organoboranes gives silylated enynes (eq 22).30 Alternatively the vinylborane resulting from reaction of a terminal alkyne with Sia2BH undergoes further reaction with an alkynyllithium to give an ate complex, oxidation of which with iodine leads to carbon-carbon bond formation (eq 23).7

Functional Group Reductions.

An unusual mix of chemo- and stereoselectivity makes Sia2BH a useful reducing agent for carbonyl compounds. While aldehydes and ketones are reduced rapidly, a variety of other functionalities including carboxylic and sulfonic acids, acid chlorides, and sulfones are inert.4 Ketone reduction is often highly stereoselective, with the bulky reducing reagent delivering hydride from the less hindered face of the carbonyl (eqs 24 and 25).5

Sia2BH is superior to Lithium Aluminum Hydride or borane for this transformation, but is generally less stereoselective than Diisopinocampheylborane. While esters are unreactive, g-lactones may be reduced to the corresponding lactols, a selectivity which has been used to advantage in carbohydrate synthesis (eq 26).31 Amides also show a unique pattern of reactivity; while Sia2BH fails to reduce primary amides, tertiary amides are converted to the corresponding aldehydes (eq 27).31

Sia2BH also reacts with a,b-unsaturated ketones, with reduction occurring in a 1,4-sense.32 The resultant boron enolate may be hydrolyzed to provide the saturated ketone (eq 28), or alternatively may be treated with an aldehyde to give syn-aldol products (eq 29).

Dicyclohexylborane, diisopinocampheylborane, and diisocaranylborane all accomplish a similar transformation; 9-BBN is inferior because it leads to significantly more 1,2-reduction.

Related Reagents.

Borane-Tetrahydrofuran; Diborane; Dicyclohexylborane.


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Thomas W. von Geldern

Abbott Laboratories, Abbott Park, IL, USA



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