Reductive bromination of aromatic aldehydes using alkylboron dibromides

Article abstract of DOI:10.1016/S0040-4039(00)00811-X

The reductive bromination of aromatic aldehydes with isopinocampheyl boron dibromide in hexane at room temperature produces the corresponding benzyl bromides in excellent yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00811-X

Tetrahedron Letters 41 (2000) 5161±5164
Reductive bromination of aromatic aldehydes using
alkylboron dibromides
George W. Kabalka,* Zhongzhi Wu and Yuhong Ju
Departments of Chemistry and Radiology, The University of Tennessee, Knoxville, TN 37996-1600, USA
Received 23 March 2000; revised 16 May 2000; accepted 17 May 2000
Abstract
The reductive bromination of aromatic aldehydes with isopinocampheyl boron dibromide in hexane at
room temperature produces the corresponding benzyl bromides in excellent yields. # 2000 Elsevier Science
Ltd. All rights reserved.
Keywords: boron and compounds; aryl halides; aldehydes; reduction.
We recently reported that aromatic aldehydes react with dialkylboron chloride derivatives to
yield 1-phenyl-1-alkanols.1 Since dialkylboron bromide derivatives are readily available, we
examined the reaction of dicyclohexylboron bromide with aryl aldehydes and found that no reaction
occurred at room temperature although reduction of the aldehyde occurred upon heating.2,3 We
then investigated the reaction of cyclohexylboron dibromide with aryl aldehydes and found that
the desired alkylation reaction also did not occur. Instead, the corresponding benzyl bromides
slowly formed.4
Formation of benzyl bromides was unexpected. Indeed, the direct conversion of aromatic
aldehydes to benzyl bromide derivatives had been achieved in only two prior instances; these
involved the use of a mixture of trimethylaminoborohydride and bromine5 or the use of a mixture
of lithium bromide, chlorotrimethylsilane, and tetramethyldisiloxane.6
* Corresponding author. Tel: (865)974-3260; fax: (865)974-2997; e-mail: kabalka@utk.edu
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00811-X

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Cyclohexene is also formed in the new reaction indicating that a reduction is occurring involving
the hydrogen beta to the boron in the cyclohexane. This is a well known reaction in organoborane
chemistry.2,3,7 15 Although a detailed mechanistic study has not yet been completed, benzyl bromide
4 could form via the bromoalkoxyborane 2 (pathway a) or via the dibromoalkoxyborane 3
(pathyway b) as outlined in Scheme 1. A preliminary carbon-13 NMR experiment would appear
to favor pathway a for reactions involving cyclohexylboron dibromide. Thus, when p-bromo-
benzylaldehyde and cyclohexylboron dibromide are mixed, a new C-13 resonance appears at 86
ppm over a period of hours. Hydrolysis at this point leads to the regeneration of the starting
material along with small quantities of benzylbromide. If the reaction mixture is not hydrolyzed,
benzylbromide 4 gradually forms. In a separate experiment, p-bromobenzaldehyde was allowed
to react with dibromoborane±dimethylsul®de to generate 3 directly (as evidenced by the appear-
ance of a C-13 resonance for the benzylic carbon at 65 ppm) and benzyl bromide 4 formed in a
matter of hours.
Scheme 1.
We reasoned that isopinocampheylboron dibromide would be more ecacious since the isopino-
campheyl group is one of the most e€ective groups for reducing carbonyl compounds via beta-
hydrogen transfer reactions. When a reaction of p-bromobenzaldehyde with isopinocampheylboron
dibromide was monitored by carbon-13 NMR, 3 was formed immediately as evidenced by the
appearance of a resonance at 65 ppm. A new resonance at 32 ppm then appeared over a period of
hours indicative of the formation of 4. Clearly, pathway b predominates when isopinocampheyl-
boron dibromide is utilized.
The reaction of isopinocampheylboron dibromide with a variety of aryl aldehydes resulted in
the formation of the corresponding benzyl bromides in excellent yields. As can be seen from the
results tabulated in Table 1, essentially, all of the aldehydes investigated were successfully con-
verted to the corresponding benzyl bromides. However, aromatic aldehydes containing strong
electron withdrawing substituents were reduced at a slower rate and generated lower yields.

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Table 1
Reductive bromination of aldehydes with isopinocampheylboron dibromidea
The reductive bromination of 4-chlorobenzaldhyde is representative: 4-chlorobenzaldehyde
(2.0 mmol, 0.28 g) was dissolved in hexane (10 mL) at room temperature in a dry ¯ask main-
tained under a nitrogen atmosphere. Isopinocampheyl±boron dibromide dimethylsul®de complex,
16
generated by re¯uxing HBBr2(SMe2) with a-pinene in CH2Cl2 (2.0 mmol, 2.0 mL of a 1.0 M
solution in CH2Cl2), was added to the aldehyde at room temperature. The reaction was allowed
to stir at room temperature for 3 h, during which time a white precipitate formed. The mixture
was then ®ltered and hydrolyzed with water, the organic layer separated, dried over anhydrous
magnesium sulfate and the product isolated by column chromatography (hexane, silica gel) to
yield 0.33g (80%) of the desired product.17
The new method provides a general, high yield synthesis of benzyl bromides from aromatic
aldehydes. The method is also useful for converting a,b-unsaturated aldehydes to the corre-
sponding bromides. However, it is not suitable for the preparation of arylalkyl bromides from
carbonyl compounds containing enolizable hydrogens.
Acknowledgements
We wish to thank the US Department of Energy and the Robert H. Cole Foundation for
support of this research.
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products partially decompose on chromatography.