Sodium Triacetoxyborohydride1

NaBH(OAc)3

[56553-60-7]  · C6H10BNaO6  · Sodium Triacetoxyborohydride  · (MW 211.96)

(the prototype of a class of NaBH(OCOR)3 reagents that are selective reducing agents for a number of functional groups1 and heterocycles;1 alkylation of amines;1-4 hydroboration1)

Physical Data: mp 116-120 °C (dec); the related NaBH3OAc has not been fully characterized.

Solubility: NaBH(OAc)3 and related acyloxyborohydrides are rapidly destroyed by H2O and protic solvents; H2 is liberated. Cosolvents that have been employed are benzene, toluene, THF, dioxane, CH2Cl2, ClCH2CH2Cl.

Form Supplied in: NaBH(OAc)3 and the related Tetramethylammonium Triacetoxyborohydride are commercially available as colorless powders.

Preparative Method: NaBH(OAc)3 and NaBH3OAc can be easily prepared in situ from the appropriate amount of acetic acid and NaBH4.

Analysis of Reagent Purity: NaBH(OAc)3 has been characterized by elemental analysis, IR, and 1H, 13C, and 11B NMR.

Handling, Storage, and Precautions: because H2 is liberated during the preparation of these reagents, all handling and storage of acyloxyborohydrides should take place under an inert atmosphere.

Functional Group Reductions.

NaBH(OAc)3 selectively reduces aldehydes but not ketones5,6 (eqs 1 and 2),7,8 even with excess reagent. However, a- and b-hydroxy ketones are reduced to the anti-diols by hydroxy-directed hydride delivery6,9,10 (eqs 3 and 4).11,12 Diastereoselectivities are generally excellent, although Me4NBH(OAc)3 seems to be a superior reagent in this regard.9 Several recent examples of NaBH(OAc)3 in the stereoselective reduction of hydroxy ketones attest to the power of this reagent.13

The hydroxy-directed NaBH(OAc)3 reduction of an imide has been described.14 The more reactive NaBH3OAc reduces enones to allylic alcohols,15 and some ketones can be reduced to alcohols with Sodium Borohydride-tartaric acid.16 The combination of NaBH4 or Sodium Cyanoborohydride-Acetic Acid serves to deoxygenate tricarbonyl systems (eq 5)17 and tosylhydrazones of ketones and aldehydes (eq 6).18 Primary and secondary amides are reduced to amines by the action of NaBH3OAc (eq 7),19,20 while tertiary amides require Sodium Trifluoroacetoxyborohydride.

Amine Alkylation (Reductive Amination).

By a pathway that may involve the generation of free aldehyde, the combination of NaBH4 and carboxylic acids is capable of N-alkylation of amines.1-4 Recent examples abound (eqs 8-11). At lower temperature, monoalkylation is generally observed (eq 8),21 while at 50-55 °C, primary and secondary amines are converted into tertiary amines (eqs 9 and 10).22,23 Neat carboxylic acid (eqs 8 and 9) or a cosolvent (eq 10) may be used. In the latter event, solid carboxylic acids function well (eq 11).24 Formic Acid may be employed for N-methylation.1,25 A useful variation is the reductive amination of aldehydes and ketones (eqs 12-14),1,26-29 a method which is claimed to be superior to that using NaBH3CN-MeOH.26 Paraformaldehyde serves as a convenient source of HCHO for N-methylation in this protocol.30,31

Carboxylic acids are reduced to alcohols with NaBH4 in THF,32 although the use of CF3CO2H in this regard is superior, and there is one report of an ester reduction to a primary alcohol with NaBH4-HOAc.33

Enamine, Imine, Iminium Ion, and Enamide Reduction.

The first reported use of NaBH4-HOAc was in the reduction of dienamines,34 and this application has found extensive use in synthesis1 (eqs 15-19).35-39

Indole Reduction.

Indole is smoothly reduced to indoline under the influence of NaBH3CN-HOAc;2 the reaction is quite general1,40 and has been employed often (eqs 20-22),41-43 especially in the synthesis of CC-1065, PDE, and analogs where only the more basic indole ring is reduced (eq 23).44,45 N-Substituted indoles are reduced to indolines with NaBH4-HOAc,1,2 and the action of NaBH4-RCO2H on N-unsubstituted indoles affords N-alkylindolines by N-alkylation of the initially formed indoline.1,2

Reduction of Other Heterocycles.

Quinolines and isoquinolines are reduced to the corresponding tetrahydro derivatives with NaBH3CN or NaBH4-RCO2H, the latter combination affording the N-alkylated compounds.1,46 Related heterocycles have been subjected to this protocol (eqs 24 and 25).47

The reduction of pyrylium salts (eq 26),48 the reductive cleavage of benzoxazoles (eq 27)49 and of saturated nitrogen heterocycles (eqs 28 and 29),1,50,51 and the reduction of other p-deficient nitrogen heterocycles1 are known.

Reduction of Oximes.

Oximes can be alkylated or reduced, depending on whether NaBH4 or NaBH3CN is employed, to give hydroxylamines1,52 (eqs 30 and 31).52,53 Oxime ethers are also reduced under these conditions,1,54 and the hydroxy-directed reduction of oxime ethers has been reported using Me4NBH(OAc)3.55 Nitriles are converted into primary amines by the tandem action of acyloxyborohydrides and alkyllithium reagents (eq 32).56

Hydroboration of Alkenes.

The second reported reaction of acyloxyborohydrides was the hydroboration of alkenes,1,57 and this reaction has been further refined.58 In a similar vein, the reduction of organomercurials by NaBH(OAc)3 has been described.59

Related Reagents.

Sodium Borohydride; Sodium Cyanoborohydride; Sodium Trifluoroacetoxyborohydride; Sodium Tris(trifluoroacetoxy)borohydride; Tetramethylammonium Triacetoxyborohydride.


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Gordon W. Gribble

Dartmouth College, Hanover, NH, USA



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