Sodium Trimethoxyborohydride1


[16940-17-3]  · C3H10BNaO3  · Sodium Trimethoxyborohydride  · (MW 127.93)

(reducing agent for various functional groups;1,2 dehalogenates vicinal dihalides;3 assists in coupling of electron-deficient alkenes with organomercurials4)

Alternate Name: sodium hydrotrimethoxyborate

Physical Data: mp 230 °C (disproportionates).

Solubility: sol isopropylamine, pyridine, morpholine, dioxane, diglyme, and THF,5 as well as HMPA2c,d and methylene chloride.2c-e However, it disproportionates rapidly in diglyme to NaBH4 (soln) and NaB(OMe)4 (ppt) or in THF to NaBH4 (ppt) and NaB(OMe)4 (soln).6 Also, methanol reacts with NaBH4 in THF only to a limited extent, with initially formed methoxyborohydrides disproportionating rapidly to NaBH4 and NaB(OMe)4 and contributing to solubilization of the otherwise insoluble NaBH4.7 Thus, disproportionation products may account for some reductions attributed to NaBH(OMe)3.

Form Supplied in: white solid.

Preparative Methods: reaction of suitably active Sodium Hydride with Trimethyl Borate at reflux;8 addition of (MeO)3B to a suspension of NaH in refluxing THF.2a

Handling, Storage, and Precautions: the solid material is stable in dry air. It reacts rapidly with strong acids and slowly with water and some alcohols. It is considered relatively safe.

Functional Group Reductions.

The reagent reduces various functional groups.2a With diethyl ether as solvent, aldehydes, ketones, acid chlorides, and acid anhydrides are readily reduced to alcohols at 35 °C. Esters and nitriles are more slowly reduced, even at 100-140 °C (dibutyl ether solvent). Carboxylic acids and carboxylates are not affected and nor are alkenes, even those in conjugation with carbonyl groups. The nitro group undergoes reaction at 140 °C but the nature of the product was not investigated. An acyl chloride may be reduced to an aldehyde selectively at -80 °C.2b

In HMPA at 70 °C, reductive displacement of halides and sulfonates occurs (Sodium Borohydride gives better results in most cases).2c,d Quantum yields in photodechlorination of chlorotoluenes are enhanced by NaBH(OMe)3 or NaBH4.2e Birch-type reduction occurs on reaction with cation radicals generated by photoelectron transfer between aromatic hydrocarbons and electron acceptors.2f

Selective Reductions.

Conjugated nitroalkenes are reduced to the corresponding nitroalkanes, with accompanying addition of the original reduction products to the parent nitroalkenes to form salts of the corresponding 1,3-dinitroalkanes (eq 1).9 In most cases, comparable results are obtained with Lithium Borohydride, NaBH4, and Lithium Aluminum Hydride.

One of two ester functions is reduced selectively (eq 2), since relative rates are primary > secondary > tertiary.10 Ketones are reduced selectively in the presence of conjugated enones, as demonstrated for conversion of androst-4-ene-3,17-dione to testosterone (eq 3).11

Iodide is displaced selectively in the presence of chloride for some 1-chloro-2-iodoperfluorocycloalkenes (eq 4).12 Even in the most reactive case (n = 1, yield 72%) there is unreacted starting material, and yields diminish with increasing n.

Stereoselective Reductions.

Stereoselectivity is reported in the reduction of some ketones.13 An example for which in situ formation of NaBH(OMe)3 is postulated13d may involve disproportionation.7 Better selectivity is usually obtained using other hydrides, most of which also are not prone to disproportionation. In stereoselective demercuration, superior results are obtained with NaBH4.14

Dehalogenation of Vicinal Dihalides.

While this is not a highly useful synthetic reaction, it is noted that NaBH(OMe)3 gives good results in some cases.3 For example, 5a,6b-dibromocholestan-3b-ol is converted to cholesterol (diglyme, 24 h, 25 °C, 80%).

Coupling of Alkylmercury(II) Salts with Electron-Deficient Alkenes.

Methoxyalkylmercury(II) chlorides, generated from the corresponding alkenes or cyclopropanes, add to various electron-deficient alkenes in the presence of NaBH(OMe)3 (eqs 5 and 6).4a,b

Yields are improved for coupling with acrylates if a 1:1 Mercury(II) Oxide-Mercury(II) Acetate mixture is used for mercuration, with the entire sequence carried out in a single flask.4c,d The electron-rich alkene may contain a nucleophilic neighboring group (eq 7).4d Enones containing isolated double bonds are converted to mercurial enones, which may then undergo reductive cyclization (eq 8).4e

Related Reagents.

Lithium Borohydride; Lithium Tri-t-butoxyaluminum Hydride; Mercury(II) Acetate-Sodium Trimethoxyborohydride; Sodium Borohydride.

1. (a) Gaylord, N. G. Reduction with Complex Metal Hydrides; Interscience: New York, 1956. (b) Reduction; Augustine, R. L., Ed.; Dekker: New York, 1968. (c) Hajos, A. Complex Hydrides and Related Reducing Agents in Organic Synthesis; Elsevier: New York, 1979. (d) Hudlicky, M. Reductions in Organic Chemistry; Horwood: Chichester, 1984.
2. (a) Brown, H. C.; Mead, E. J. JACS 1953, 75, 6263. (b) Fuchs, W. CB 1955, 88, 1825 (CA 1956, 50, 16 681e). (c) Hutchins, R. O.; Kandasamy, D.; Dux, F., III; Maryanoff, C. A.; Rotstein, D.; Goldsmith, B.; Burgoyne, W.; Cistone, F.; Dalessandro, J.; Puglis, J. JOC 1978, 43, 2259. (d) Jung, M. E.; Usui, Y.; Vu, C. T. TL 1987, 28, 5977. (e) Epling, G. A.; Florio, E. M. JCS(P1) 1988, 703. (f) Yasuda, M.; Pac, C.; Sakurai, H. Kokagaku Toronkai Koen Yoshishu 1979, 262 (CA 1980, 93, 94 535y).
3. King, J. F.; Allbutt, A. D.; Pews, R. G. CJC 1968, 46, 805.
4. (a) Geise, B.; Heuck, K. CB 1979, 112, 3759 (CA 1980, 92, 93 872y). (b) Geise, B.; Zwick, W. CB 1979, 112, 3766 (CA 1980, 92, 197 972x). (c) Geise, B.; Heuck, K. TL 1980, 21, 1829. (d) Geise, B.; Heuck, K. CB 1981, 114, 1572 (CA 1981, 95, 24 759s). (e) Danishefsky, S.; Chackalamannil, S.; Uang, B.-J. JOC 1982, 47, 2231.
5. Schlesinger, H. I.; Brown, H. C.; Finholt, A. E. JACS 1953, 75, 205.
6. (a) Brown, H. C.; Mead, E. J.; Shoaf, C. J. JACS 1956, 78, 3616. (b) Brown, H. C.; Mead, E. J.; Tierney, P. A. JACS 1957, 79, 5400.
7. Golden, J. H.; Schreier, C.; Singaram, B.; Williamson, S. M. IC 1992, 31, 1533.
8. Brown, H. C.; Schlesinger, H. I.; Sheft, I.; Ritter, D. M. JACS 1953, 75, 192.
9. Schecter, H.; Ley, D. E.; Roberson, E. B., Jr. JACS 1956, 78, 4984.
10. Bell, R. A.; Gravestock, M. B. CJC 1969, 47, 2099.
11. Norymberski, J. K.; Woods, G. F. JCS 1955, 3426.
12. Natarajan, S.; Soulen, R. L. JFC 1981, 17, 447.
13. (a) Dauben, W. G.; Fonken, G. J.; Noyce, D. S. JACS 1956, 78, 2579. (b) Vail, O. R.; Wheeler, D. M. S. JOC 1962, 27, 3803. (c) Kruger, D.; Sopchik, A. E.; Kingsbury, C. A. JOC 1984, 49, 778. (d) Tonnis, J. A.; Wnuk, T. A.; Dolan, M. J.; Kovacic, P. JOC 1974, 39, 766.
14. Gouzoules, F. H.; Whitney, R. A. JOC 1986, 51, 2024.

John L. Hubbard

Marshall University, Huntington, WV, USA

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