Lithium 9-boratabicyclo[3.3.1]nonane1

[76448-08-3]  · C8H16BLi  · Lithium 9-boratabicyclo[3.3.1]nonane  · (MW 129.99)

(selective reducing agent for esters, aldehydes, ketones, primary halides and tosylates, epoxides, aromatic nitriles, and tertiary amides; catalyst for LiBH4 reduction of esters; with 9-BBN-H, reduces carboxylic acids to aldehydes)

Alternate Name: Li(H2-9-BBN).

Physical Data: colorless in THF solution.

Solubility: sol THF; evolves H2 in protic solvents.2

Form Supplied in: 1.0 M solution in THF.

Analysis of Reagent Purity: 11B NMR resonance in THF at d -17.4 (t, J = 72.1 Hz) ppm.2a

Handling, Storage, and Precautions: THF solutions of the reagent are stable indefinitely at 25 °C when stored under N2; exposure to O2, H2O, or protic solvents results in its potentially dangerous rapid oxidation and/or the exothermic generation of H2; its generation and use involves handling air-sensitive reagents (i.e. LiH, 9-Borabicyclo[3.3.1]nonane); use in a fume hood.1

Selective Reductions.

The reagent is conveniently prepared from an excess of LiH and 9-BBN in THF (48 h, 65 °C)2 and is omnipresent as a byproduct from the reaction of alkyllithium reagents with 9-BBN.3 Its reactivity with representative compounds containing different functional groups has been surveyed.2b Primary alcohols, phenols, and aliphatic and aromatic thiols react with excess reagent in THF at 25 °C with rapid and quantitative H2 evolution. However, n-hexylamine is unreactive, and secondary and tertiary alcohols react very slowly under these conditions. The reagent reduces acid chlorides, esters, lactones, aldehydes, and even highly substituted ketones to the corresponding alcohols (eq 1), but anhydrides are only reduced to an equimolar mixture of alcohol and carboxylate. Cinnamaldehyde undergoes clean 1,2-reduction to produce cinnamyl alcohol. Epoxides are reductively opened from the least substituted side while acetals and orthoesters are inert to the reagent. Treatment of primary amides with Li(H2-9-BBN) leads only to slow H2 evolution, whereas caprolactam is reduced slowly and tertiary amides are reduced to the corresponding amines (24 h, 25 °C). Aromatic nitriles are also reduced to the amine under these conditions, but aliphatic nitriles react sluggishly. Isocyanates are reduced to formamides while treatment of oximes results only in H2 evolution. Azobenzene is essentially inert to the reagent, while pyridine, azoxybenzene, and nitropropane are partially reduced. Nitrobenzene and pyridine N-oxide are reduced, but the actual products have not been determined. Disulfides are reduced to thiolates, while sulfoxides, sulfones, sulfonic acids, and sulfides are inert. The reduction of n-alkyl derivatives follows the order: I > OTs > Br >> Cl, whereas secondary bromides and tosylates are not effectively reduced at 25 °C. B-Halo-9-BBN derivatives are also conveniently reduced to 9-BBN by the reagent.4

Catalyst for the LiBH4 Reduction of Esters.

The reduction of ethyl caproate by Li(H2-9-BBN) is rapid in THF (1 h, 25 °C), while its reduction by Lithium Borohydride is significant slower (ca. 50% in 8 h, 25 °C). With 10 mol % of Li(H2-9-BBN) or B-MeO-9-BBN as well as other organoboranes as catalysts, a markedly enhanced rate of reduction of esters by LiBH4 in THF (8 h, 25 °C) or ether (eq 2) is observed.5 A modest catalytic effect is observed for epoxides and primary tosylates, and the reduction of benzonitrile by LiBH4 is observed only with added catalyst. n-Octyl bromide is not reduced under catalytic conditions, but is reduced slowly by using stoichiometric amounts of Li(H2-9-BBN) (6 h, 25 °C). This reagent may be the active species in these catalytic reductions.

Aldehydes from Carboxylic Acids.6

The reaction of 9-BBN with carboxylic acids evolves H2, producing the corresponding acyloxy-9-BBN derivative which, upon treatment with Li(H2-9-BBN) at room temperature, gives high yields of the corresponding aldehydes (76-99%). The procedure is widely applicable, being effective for both aromatic and aliphatic substrates (eq 3). Dicarboxylic acids are also reduced to dialdehydes efficiently (eq 4), and the process tolerates aromatic functionality (e.g. Cl, NO2, OMe).

Related Reagents.

Lithium Borohydride; Lithium 9,9-Dibutyl-9-borabicyclo[3.3.1]nonanate; Potassium 9-Siamyl-9-boratabicyclo[3.3.1]nonane.

1. (a) Pelter, A.; Smith, K.; Brown, H. C. Borane Reagents; Academic: London, 1988. (b) Brown, H. C.; Midland, M. M.; Levy, A. B.; Kramer, G. W. Organic Synthesis via Boranes; Wiley: New York, 1975.
2. (a) Brown, H. C.; Singaram, B.; Mathew, C. P. JOC 1981, 46, 2712. (b) Brown, H. C.; Mathew, C. P.; Pyun, C.; Son, J. C.; Yoon, Y. M. JOC 1984, 49, 3091.
3. Hubbard, J. L. Kramer, G. W.; JOM 1978, 156, 81.
4. Brown, H. C.; Kulkarni, S. U. JOM 1981, 218, 299.
5. (a) Brown, H. C.; Narasimham, S. JOC 1982, 47, 1604. (b) Brown, H. C.; Narasimham, S. JOC 1984, 49, 3891.
6. Cha, S. S.; Kim, J. E.; Oh, S. Y.; Kim, J. D. TL 1987, 28, 4575.

John A. Soderquist & Luis A. Manzanares

University of Puerto Rico, Rio Piedras, Puerto Rico

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.