Potassium Tri-s-butylborohydride1


[54575-49-4]  · C12H28BK  · Potassium Tri-s-butylborohydride  · (MW 222.31)

(reducing agent for various functional groups;2 selective reducing agent;3-7 stereoselective reducing agent for ketones;8-10 used for reduction of conjugated enones;11 regioselective reducing agent for cyclic anhydrides;12 reacts with carbon monoxide in the presence of free trialkylborane;13 used for stereoselective synthesis of cis-alkenylboranes14)

Alternate Names: K-Selectride®; potassium hydrotris(1-methylpropyl)borate.

Physical Data: not isolated; prepared and used in solution.

Solubility: solubility limits have not been established. The reagent is normally used as a 1.0 M solution in THF or Et2O, but use of toluene as solvent is also reported.

Form Supplied in: 1.0 M solutions in THF or Et2O.

Analysis of Reagent Purity: solutions of pure reagent exhibit doublets (J = 68-71 Hz) centered in the range d -7.1 to d -7.5 in the 11B NMR spectrum.15,16a,17 Concentration of hydride is determined by hydrolysis of aliquots and measurement of the hydrogen evolved or by quenching aliquots in excess 1-iodooctane and analysis of the octane formed by GLC.18 Concentration of boron is verified by oxidizing aliquots using alkaline hydrogen peroxide and analyzing the 2-butanol formed by GLC.19

Preparative Methods: direct reaction of tris(1-methylpropyl)borane with Potassium Hydride is satisfactory,15 especially with activated KH.16 The reagent is also formed by reaction of the trialkylborane with Potassium Triisopropoxyborohydride.17

Handling, Storage, and Precautions: solutions are air- and water-sensitive and should be handled in a well ventilated hood under an inert atmosphere using appropriate techniques.20 Potentially pyrophoric tris(1-methylpropyl)borane is a byproduct of reductions; thus standard organoborane oxidation19 is recommended as part of the workup.

Functional Group Reductions.

The reducing characteristics of the reagent have been studied systematically.2a At 0 °C it liberates H2 quantitatively with various active hydrogen compounds, including primary alcohols, phenols, thiols, carboxylic acids, primary amides, aliphatic nitro compounds, and oximes. Secondary and tertiary alcohols and primary amines are inert. Carboxylic acids, amides, nitro compounds, and oximes are not reduced further. Aldehydes, ketones, and acyl chlorides are reduced rapidly to the alcohol stage. Acyclic esters are reduced more slowly, but lactones are rapidly reduced to diols. Cyclic anhydrides are reduced to lactones if steps are taken to avoid further reduction of the latter. Terminal epoxides are reduced rapidly and cleanly to the Markovnikov alcohols. Internal epoxides are reduced slowly. Nitriles are reduced sluggishly. Pyridine and quinoline consume hydride, but the products have not been characterized. Disulfides are reduced to thiols. Primary iodides and bromides are reduced rapidly, chlorides more slowly. Cyclohexyl bromide and tosylate react sluggishly.

A reagent derived by adding 2 equiv of K-Selectride to 1 equiv of CuI effectively displaces halide from various aryl halides, and in one example an internal alkyne, dec-5-yne, is converted predominantly to the (Z)-alkene (Z:E = 88:12).2b

Selective Reductions.

Ketones are reduced selectively in the presence of other functional groups: esters,3 including methyl esters3a,d and g-lactones;3b a cyclic carbamate;4 amides5 including 2-acetyl b-lactams5a-c and benzenesulfonamides;5f azides;6 and internal epoxides.3d Steroid 3,17- or 3,20-dione systems undergo selective reduction at the 3-position,7 as does a 5-ene-3,17-dione system.11c Conjugated enones are reduced selectively in the presence of esters.11e-g

Stereoselective Reductions.

Like L-Selectride (Lithium Tri-s-butylborohydride), K-Selectride is useful for diastereoselective reduction of alkyl-substituted cyclic ketones to alcohols.15a Other applications to various types of cyclic ketones have been reported.3d,4,7,8 Diastereoselective reduction is also observed for acyclic ketones,9 including keto esters,3a-c keto amides,5 and a keto azide.6 A chiral dione is diastereoselectively reduced to a diol.10

Various theoretical models are used to rationalize observed diastereoselectivity.21 In simple cases, the bulk of the reagent appears to dictate that hydride approach from the less sterically hindered face of the carbonyl.15a However, complexation effects of heteroatoms,8a crown ethers,3c,9i and cryptands9i may reverse the direction of approach. Also, the coordinating ability of the solvent influences the ratio of diastereomers.3b

Reduction of Conjugated Enones.

A reasonably systematic study of conjugated enone reductions has been conducted.11a Acyclic enones undergo 1,2-addition with stereoselective formation of allylic alcohols upon protonation. Cyclohexenones with no b-substitution yield saturated ketones as a consequence of 1,4-addition with 1 equiv of hydride, while a b-methyl results in exclusive 1,2-addition; 3 equiv of hydride results in stereoselective formation of saturated alcohols. Both cyclopentenones and cycloheptenones give mixtures of products. The enolate resulting from 1,4-addition may be alkylated instead of protonated, but this a-alkylation appears to work better with L-Selectride. Attempted reduction of a,b-unsaturated esters leads to Claisen condensation products.

Further examples of 1,2-addition to cyclohexenones involve the 5-en-3-one function of steroids11b,c or analogous systems.11b This is reduced selectively in 2a-fluoro-4-androstene-3,17-dione.11c Stereoselectivity in reduction of testosterone, which yields predominantly the 3b,17b-diol (3b:3a = 88:12), is reversed for 2a-fluorotestosterone, which yields exclusively the 3a,17b-diol.11c

A conjugated cyclohexadienone undergoes 1,4-addition so that only the a,b-double bond is reduced.11d Stereoselectivity results on 1,4-addition to (S)-(+)-carvone (eq 1).11e

An enone incorporated into a 14-membered macrolide undergoes stereoselective 1,2-addition while the lactone is not affected.11f With 3 equiv of K-Selectride, the cyclopentenone in the prostanoid 15(S)-PGA2 is reduced stereoselectively to the corresponding cyclopentanol while a methyl ester remains untouched.11g A procedure utilizing 2 equiv of K-Selectride in the presence of 2 equiv of ethanol reduces a cyclohexenone stereoselectively to the cyclohexanol in the presence of methyl ester, acetate, and g-lactone functions (eq 2).11h An a,b-alkynic ketone undergoes exclusive 1,2-addition with stereoselective formation of the propargylic alcohol.9b

Regioselective Reduction of Cyclic Anhydrides.

Various succinic and phthalic anhydrides are reduced by the reagent to lactones.12 With certain exceptions (eq 3),12b reduction occurs preferentially at the less hindered carbonyl function. A mechanistic interpretation of the results has been proposed.12b,e

Reaction with Carbon Monoxide.

Carbonylation of KBH-(s-Bu)3 followed by treatment with refluxing aqueous Sodium Hydroxide yields 2-methyl-1-butanol.13a It is now evident that KBH(s-Bu)3 is an intermediate in the hydride-induced carbonylation of s-Bu3B using Potassium Triisopropoxyborohydride,13b,17 so that different workup procedures may produce 2-methylbutanal13c or 3,5-dimethyl-4-heptanol.13d

Stereoselective Synthesis of cis-Alkenylboranes.

Reaction of 1-halo-1-alkenylboranes with KBH(s-Bu)3 produces cis-alkenylboranes, but the ease of removing triethylborane makes Lithium Triethylborohydride the reagent of choice.14

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John L. Hubbard

Marshall University, Huntington, WV, USA

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