Potassium Triisopropoxyborohydride1


[42278-67-1]  · C9H22BKO3  · Potassium Triisopropoxyborohydride  · (MW 228.22)

(mild reducing agent for carbonyl compounds,1 disulfides,2c,3 and haloboranes2a-c)

Alternate Name: KIPBH.

Physical Data: d (1.0 M THF solution) 0.912 g cm-3.

Solubility: sol THF, Et2O, monoglyme.2

Form Supplied in: no longer commercially available (formerly available as 1.0 M THF soln).

Analysis of Reagent Purity: IR (THF): 2210 cm-1 (nB-H), 1375 cm-1 (nB-O). 11B NMR (THF; BF3.Et2O as ref, with d downfield from BF3.Et2O assigned as positive): 6.1 d (d, JB -H 118 Hz).2 Samples can be hydrolyzed with H2O and K and B contents measured as KOH and H3BO3, while hydride concentration can be estimated by measuring the H2 evolved from acidic hydrolysis,2 and isopropoxide can be evaluated by GLC analysis as i-PrOH.2a

Preparative Methods: THF solutions can be obtained by adding 1.0 mol of freshly distilled Triisopropyl Borate to 1.5 mol of Potassium Hydride suspended in 400 ml of solvent.2c Solutions in Et2O or monoglyme were prepared in a similar way.2a

Purification: if THF solutions are contaminated by K(i-PrO)4B, they can be purified by gentle reflux over an excess of KH for about 24 h.2

Handling, Storage, and Precautions: the solution must be stored under N2 in the absence of moisture, but it is quite stable to disproportionation (over 6 months, when stored in the presence of a slight excess of KH at ambient temperature2a). It is incompatible with strong oxidizing agents, water, and acids (H2 is evolved).

General Considerations.

Potassium triisopropoxyborohydride, in contrast to the less hindered trialkoxyborohydrides, is stable in THF solution toward disproportionation. It is a mild reducing agent, similar to Sodium Borohydride in that it reduces only aldehydes and ketones while almost all other functional groups are unaffected. KIPBH offers some advantages over simple borohydrides: it is soluble in nonhydroxylic solvents, it is more chemo- and stereoselective, and its kinetics are easier to study since it carries only 1 equiv of hydride per molecule.1,2b

Active hydrogen compounds (alcohols, phenols, thiols, amines, carboxylic acids) evolved H2 sluggishly when treated with KIPBH in THF at 0 °C.2c Anhydrides, acyl chlorides, esters, lactones, epoxides, amides, nitriles, nitro compounds, oximes, isocyanates, quinones are not cleanly reduced by KIPBH. With few exceptions, most of these functional groups are completely unaffected by KIPBH.2c

Reduction of Carbonyl Compounds.

Both aldehydes and ketones are rapidly reduced to the corresponding alcohols by KIPBH, even at temperatures below 0 °C.2b-c,4 Unsaturated carbonyl compounds are usually reduced to allylic alcohols (1,2-attack).2c KIPBH is particularly efficient for the diastereoselective reduction of cyclic ketones. The less stable cis epimer (from axial attack) is usually obtained in high diastereomeric excess (up to 96% de),2c,4 but even better results can be obtained using other complex boro- or aluminium hydrides.2b,d,4,5

Chiral 2-oxo esters (from (-)-8-phenylmenthol6a or (-)-menthol6b,c) have been reduced to the corresponding 2-hydroxy esters (up to 90% de) by using KIPBH in THF. The new chiral center has the (R) configuration (eq 1). It is worth noting that, by using the same chiral auxiliary, addition of the Grignard reagent to the aldehyde or reduction of the ketone affords products with opposite configuration.6a In some examples, better diastereoselectivity can be obtained using other complex boro- or aluminum hydrides.6b,c Similarly, the anti diastereoselective reduction of chiral 2-alkyl-3-oxoamides6d (from trans-2,5-bis(methoxymethoxymethyl)pyrrolidine) can be performed in high de by using KIPBH, but Potassium Triethylborohydride gives the best results.

Reduction of Disulfides.

Both aryl and alkyl disulfides are reduced to the corresponding thiols by KIPBH in THF at 0 °C.2c,3 Aromatic disulfides can be selectively reduced in the presence of aliphatic ones.3 Other reducing reagents (LiAlH4, NaBH4/AlCl3, NaBH4, Zn/AcOH) suffer serious disadvantages, since they are either less chemoselective or give rise to heterogeneous systems.

Reduction of Heterocycles.

KIPBH has been tested (along with other boro- and aluminum hydrides) in the Fowler synthesis of dihydropyridines (eq 2), i.e. the reduction of the N-alkoxycarbonylpyridinium ions (1) formed in situ from a pyridine and a chloroformate ester.7 The regiochemistry of the reduction depends mainly on the ring substituents. Sterically undemanding donor substituents favor reduction at C-2, despite the bulkiness of the reductant. However, branched substituents are more sensitive to steric factors in the hydride and acceptor substituents are poorly regiodirective.

Applications to Boron Chemistry.

Although KIPBH is a very mild reducing agent, it is very effective in reducing haloboranes. This reaction has been used to synthesize unsymmetrically substituted trialkylboranes, from which unsymmetrical ketones can be obtained via carbonylation or cyanidation (eq 3).2c,8 In contrast to the method using Thexylborane, terminal alkenes can be employed in the reaction with thexylchloroborane and many different functional groups may be present in the alkenes introduced in the third step. The overall process is best carried out if the reduction of the thexylalkylborane (2) is performed in the presence of the second alkene. Use of a diene allows the synthesis of cyclic ketones.8

Reaction of KIPBH with (Z)-(1-bromo-1-alkenyl)boronic esters (obtained from reaction of 1-bromoalkynes with dibromoborane, followed by treatment of the resulting alkenyldibromoboranes with an alcohol) in Et2O at ambient temperature provides a rapid access to stereochemically pure (Z)-1-alkenylboronic esters (3) (eq 4).2b-c,9 These intermediates have found broad application in the stereoselective synthesis of arylated alkenes, conjugated alkadienes,9b conjugated dienones,9c and conjugated alkanedienoates9d via palladium-catalyzed cross-coupling reactions with aryl iodides, 1-bromoalkenes, 3-halo-2-alken-1-ones, and 3-bromo-2-alkenoates, respectively. Moreover, (Z)-1-alkenylboronic esters (3) can be employed in the synthesis of stereochemically defined (E)-1-bromo-1-alkenes (via reaction with Br2, followed by treatment with MeONa) and (Z)-1-iodo-1-alkenes (via reaction with NaOH/I2).9e

One-carbon homologation of boronic esters can be realized through reaction with Dichloromethyllithium, followed by in situ reduction with KIPBH.10 This procedure is of value in permitting the synthesis of boron derivatives not directly available through hydroboration and can be applied also to a-chiral boronic esters in order to obtain b-chiral boronic esters in an enantiospecific manner.10b,c The KIPBH reduction of a-chloro boronic esters is thought to proceed through the intermediate formation of the corresponding borohydride.10b

KIPBH is also effective in the carbonylation of organoboranes at 0 °C to obtain aldehydes or primary alcohols.11 This reagent is superior to complex aluminum hydrides (lithium trimethoxyaluminum hydride and Lithium Tri-t-butoxyaluminum Hydride, for example) because of its greater stability, chemoselectivity, and its simpler workup (no gelatinous precipitates). LiBH4 undergoes the same reaction at ambient temperature.

KIPBH rapidly transfers hydride even to severely hindered trialkylboranes, which fail to react with KH, providing a convenient route to highly hindered potassium trialkylborohydrides.2c,12


Transition metal formyl complexes can be prepared by reaction of transition metal carbonyl compounds with KIPBH.12,13a-c

Other uses of KIPBH in organometallic chemistry have been reported.13d,e

1. (a) Brown, H. C.; Krishnamurty, S. Aldrichim. Acta 1979, 12, 3. (b) Brown, H. C.; Krishnamurty, S. T 1979, 35, 567. (c) COS 1991, 3, Section; COS 1991, 8, Sections,, (d) Seyden-Penne, J. Reductions by the Alumino- and Borohydrides in Organic Synthesis; VCH-Lavoiser: Paris, 1991.
2. (a) Brown, H. C.; Nazer, B.; Sikorski, J. A. OM 1983, 2, 634. (b) Brown, H. C.; Cha, J. S.; Nazer, B. IC 1984, 23, 2929. (c) Brown, H. C.; Cha, J. S.; Nazer, B.; Kim, S.-C.; Krishnamurthy, S.; Brown, C. A. JOC 1984, 49, 885. (d) Cha, J. S.; Kim, J. E.; Lee, J. C.; Yoon, M. S. Bull. Korean Chem. Soc. 1986, 7, 66.
3. Brown, H. C.; Nazer, B.; Cha, J. S. S 1984, 498.
4. Brown, C. A.; Krishnamurthy, S.; Kim, S. C. CC 1973, 391.
5. Yoon, N. M.; Kim, K. E.; Kang, J. JOC 1986, 51, 226.
6. (a) Whitesell, J. K.; Deyo, D.; Bhattacharya, A. CC 1983, 802. (b) Boireau, G.; Deberly, A. TA 1991, 2, 771. (c) Solladié-Cavallo, A.; Bencheqroun, M. TA 1991, 2, 1165. (d) Ito, Y.; Katsuki, T.; Yamaguchi, M. TL 1985, 26, 4643.
7. Sundberg, R. J.; Hamilton, G.; Trindle, C. JOC 1986, 51, 3672.
8. (a) Kulkarni, S. U.; Lee, H. D.; Brown, H. C. JOC 1980, 45, 4542. (b) Welch, M. C.; Bryson, T. A. TL 1989, 30, 523.
9. (a) Brown, H. C.; Imai, T. OM 1984, 3, 1392. (b) Miyaura, N.; Satoh, M.; Suzuki, A. TL 1986, 27, 3745. (c) Satoh, N.; Ishiyama, T.; Miyaura, N.; Suzuki, A. BCJ 1987, 60, 3471. (d) Yanagi, T.; Oh-e, T.; Miyaura, N.; Suzuki, A. BCJ 1989, 62, 3892. (e) Brown, H. C.; Somayaji, V. S 1984, 919.
10. (a) Brown, H. C.; Naik, R. G.; Singaram, B.; Pyun, C. OM 1985, 4, 1925. (b) Brown, H. C.; Naik, R. G.; Bakshi, R. K.; Pyun, C.; Singaram, B. JOC 1985, 50, 5586. (c) Brown, H. C.; Singh, S. M. OM 1986, 5, 994.
11. (a) Brown, H. C.; Hubbard, J. L.; Smith, K. S 1979, 701. (b) Hubbard, J. L.; Smith, K. JOM 1984, 276, C41.
12. Brown, C. A.; Hubbard, J. L. JACS 1979, 101, 3964.
13. (a) Casey, C. P.; Neumann, S. M. JACS 1976, 98, 5395. (b) Steinmetz, G. R.; Geoffroy, G. L. JACS 1981, 103, 1278. (c) Berke, H.; Huttner, G.; Scheidsteger, O.; Weiler, G. AG(E) 1984, 23, 735. (d) Casey, C. P.; Polichnowski, S. W. JACS 1977, 99, 6097. (e) Burch, R. R.; Muetterties, E. L.; Thompson, M. R.; Day, V. W. OM 1983, 2, 474.

Luca Banfi, Enrica Narisano & Renata Riva

Università di Genova, Italy

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