[5158-50-9]  · C2H6BBr2  · Bromodimethylborane  · (MW 120.78)

(mild Lewis acid capable of selective cleavage of ethers2,3 and acetals;4,5 deoxygenation of sulfoxides6)

Physical Data: mp -129 °C; bp 31-32 °C; d 1.238 g cm-3; fp -37 °C.

Solubility: sol dichloromethane, 1,2-dichloroethane, hexane.

Form Supplied in: colorless liquid.

Preparative Method: can be conveniently prepared by treating Tetramethylstannane with Boron Tribromide.7

Handling, Storage, and Precautions: flammable liquid, moisture sensitive; typically stored and dispensed as a 1.5-2 M solution in dichloromethane or dichloroethane. Solutions of this sort are stable for a period of months if stored at -15 °C and properly protected from moisture.

Cleavage of Ethers.

Bromodimethylborane (Me2BBr) reacts with primary, secondary, and aryl methyl ethers,2 in addition to trityl,8 benzyl,2,8 and 4-methoxybenzyl9 ethers, to regenerate the parent alcohol in good to excellent yield (e.g. eq 1). The tertiary methyl ethers examined afforded the corresponding tertiary bromides.2 The reaction is typically carried out in dichloromethane or 1,2-dichloroethane between 0 °C and rt, in the presence of 1.3-4 equiv of Me2BBr. The reaction is usually complete in a matter of hours. Triethylamine (0.1-0.15 equiv per equiv of Me2BBr) is often added as an acid scavenger. 4-Methoxybenzyl ethers are more reactive and are cleaved at -78 °C, whereas aryl methyl ethers require elevated temperatures to react. Other functional groups including acetates, benzoates, alcohols, ethyl esters, and t-butyldiphenylsilyl ethers are recovered unchanged under the standard reaction conditions.

Bromodimethylborane is also effective for the cleavage of cyclic ethers.2,3 Epoxides react at -78 °C while the analogous four- to seven-membered ring heterocycles react between 0 °C and rt. In contrast to other boron-containing Lewis acids, Me2BBr reacts via a predominantly SN2 mechanism. Tetrahydrofuran derivatives which are substituted at the 2-position give rise to primary bromides as the major or exclusive products. The nature of the substituent has a quantitative influence on the outcome of the reaction via steric effects and/or complexation to the reagent. It is of interest to note that tetrahydrofurans can be cleaved in the presence of acyclic ethers (eq 2).3

It is also of considerable interest to note that no b-elimination of the hydroxy group was observed in the ring-opening of 2-(ethoxycarbonylmethyl)tetrahydrofurans (eq 3),3 whereas C-glycosides bearing more acidic protons on the aglycon react with Me2BBr to generate acyclic alkenes (eq 4).10

Bromodimethylborane has also been used in conjunction with Tetra-n-butylammonium Iodide to bring about the fragmentation of iodomethyl ether derivatives (eq 5).11

Cleavage of Acetals.4,5

Cyclic and acyclic acetals react with Me2BBr at -78 °C to generate the parent aldehydes and ketones in excellent yield (e.g. eq 6). Primary, secondary, and tertiary (2-methoxyethoxy)methyl (MEM), methoxymethyl (MOM), and (methylthio)methyl (MTM) ethers also react at -78 °C to give, after aqueous workup, the corresponding alcohol. It is interesting to note that even tertiary MEM ethers cleanly regenerate the parent alcohol without formation of the corresponding bromide or elimination products (eq 7). Treatment of an acetonide with Me2BBr gives the parent diol in high yield (eq 8).

Tetrahydropyranyl (THP) and tetrahydrofuranyl (THF) ethers are converted to the corresponding alcohols by Me2BBr at rt (eq 9), although the acetals are cleaved at -78 °C (see below).

Bromodiphenylborane (Ph2BBr) and 9-Bromo-9-borabicyclo[3.3.1]nonane (Br-9-BBN) can often be used in place of Me2BBr for the cleavage of acetals;4,5 however, the purification of products from reactions employing Me2BBr is facilitated by the volatility of Me2B-containing byproducts, thus making Me2BBr the reagent of choice in most instances.

Interconversion of Functional Groups.

The reaction of Me2BBr with MEM and MOM ethers is believed to proceed via a-bromo ether intermediates. It is possible to trap these intermediates with nucleophiles such as thiols, alcohols, and cyanide. An example of the utility of this sequence is the conversion of a readily prepared MOM ether into an MTM ether (eq 10).12

While THP and THF ethers are converted to the corresponding alcohols by Me2BBr at rt, the acetal is cleaved at -78 °C.13 The initial products of the reaction are acyclic a-bromo ethers. These can be trapped with a variety of nucleophiles to generate stable ring-opened products (eq 11).13 This reaction has been extended to glycosides which, although less reactive, behave in a similar fashion.14,15

Benzylidene acetals are recovered unchanged when treated with Me2BBr under conditions which are used to cleave other acetals.16 It is, however, possible to cleave benzylidene acetals to generate hydroxy-O,S-acetals in excellent yield, by treatment with Me2BBr at -78 °C followed by Thiophenol (eq 12).16 Sterically encumbered bromoboranes optimize regioselective complexation of boron to the least hindered oxygen atom and are, therefore, the reagents of choice for this process (eq 12).16 These experiments demonstrate that benzylidene acetals do indeed react with Me2BBr at -78 °C, like other acetals.

Treatment of glycoside benzylidene acetals with a variety of disubstituted bromoboranes, followed by Borane-Tetrahydrofuran, generates 4-O-benzyl-6-hydroxypyranosides in excellent yield (eq 13).16

Acetals derived from Dimethyl L-Tartrate react with Me2BBr to generate a-bromo ethers which react further with cuprate reagents to give optically active secondary alcohol derivatives (eq 14).17 The alcohols may be liberated by treatment with Samarium(II) Iodide or by a straightforward sequence of reactions (mesylation and elimination to form an enol ether followed by exposure to methoxide in refluxing methanol). Selectivity is enhanced by the use of Ph2BBr and by careful control of the reaction temperature at each step.

Miscellaneous Reactions.

Bromodimethylborane can also be used to convert dialkyl, aryl alkyl, and diaryl sulfoxides to the corresponding sulfides (eq 15).6 Typically, the sulfoxides are treated with 2.5 equiv of Me2BBr in dichloromethane at -23 °C for 30 min and at 0 °C for 10 min. Bromine is produced in the reaction and must be removed in order to avoid possible side reactions. This is accomplished by saturating the solution with propene prior to introducing the reagent or by adding cyclohexene. Phosphine oxides and sulfones failed to react under the conditions used to deoxygenate sulfoxides.

Bromodimethylborane has also been used as a catalyst for the Pictet-Spengler reaction (eq 16)18 and to catalyze the 1,3-transposition of an allylic lactone.19

1. Guindon, Y.; Anderson, P. C.; Yoakim, C.; Girard, Y.; Berthiaume, S.; Morton, H. E. PAC 1988, 60, 1705.
2. Guindon, Y.; Yoakim, C.; Morton, H. E. TL 1983, 24, 2969.
3. Guindon, Y.; Therien, M.; Girard, Y.; Yoakim, C. JOC 1987, 52, 1680.
4. Guindon, Y.; Morton, H. E.; Yoakim, C. TL 1983, 24, 3969.
5. Guindon, Y.; Yoakim, C.; Morton, H. E. JOC 1984, 49, 3912.
6. Guindon, Y.; Atkinson, J. G.; Morton, H. E. JOC 1984, 49, 4538.
7. Nöth, H.; Vahrenkamp, H. JOM 1968, 11, 399.
8. Kodali, D. R.; Duclos Jr., R. I. Chem. Phys. Lipids 1992, 61, 169.
9. Hébert, N.; Beck, A.; Lennox, R. B.; Just, G. JOC 1992, 57, 1777.
10. Abel, S.; Linker, T.; Giese, B. SL 1991, 171.
11. Gauthier, J. Y.; Guindon, Y. TL 1987, 28, 5985.
12. Morton, H. E.; Guindon, Y. JOC 1985, 50, 5379.
13. Guindon, Y.; Bernstein, M. A.; Anderson, P. C. TL 1987, 28, 2225.
14. Guindon, Y.; Anderson, P. C. TL 1987, 28, 2485.
15. Hashimoto, H.; Kawanishi, M.; Yuasa, H. TL, 1991, 32, 7087.
16. Guindon, Y.; Girard, Y.; Berthiaume, S.; Gorys, V.; Lemieux, R.; Yoakim, C. CJC 1990, 68, 897.
17. Guindon, Y.; Simoneau, B.; Yoakim, C.; Gorys, V.; Lemieux, R.; Ogilvie, W. TL 1991, 32, 5453.
18. Kawate, T.; Nakagawa, M.; Ogata, K.; Hino, T. H 1992, 33, 801.
19. Mander, L. N.; Patrick, G. L. TL 1990, 31, 423.

Yvan Guindon & Paul C. Anderson

Bio-Méga/Boehringer Ingelheim Research, Laval, Québec, Canada

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