Preparation of functionalized alkenylmagnesium bromides via a bromine- magnesium exchange

Article abstract of DOI:10.1016/S0040-4039(00)00387-7

α-Bromonitriles, such as 1, 2 or the α-bromosulfone 3, undergo a smooth bromine-magnesium exchange with isopropylmagnesium bromide furnishing new functionalized organomagnesium species which react smoothly with various electrophiles like Me₃SiCl, Bu₃SnCl, allyl bromides, aldehydes, ketones or acid chlorides providing the expected products of type 7, 8 or 9. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00387-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3319–3322
Preparation of functionalized alkenylmagnesium bromides via a
bromine–magnesium exchange
∗
Jérôme Thibonnet and Paul Knochel
Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, D-81377 München, Germany
Received 21 February 2000; accepted 29 February 2000
Abstract
α-Bromonitriles, such as 1, 2 or the α-bromosulfone 3, undergo a smooth bromine–magnesium exchange with
isopropylmagnesium bromide furnishing new functionalized organomagnesium species which react smoothly with
various electrophiles like Me3SiCl, Bu3SnCl, allyl bromides, aldehydes, ketones or acid chlorides providing the
expected products of type 7, 8 or 9. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: magnesium; functionalized organometallics; nitrile; sulfone.
Functionalized organometallics are important building blocks for the preparation of elaborated poly-
1
functional molecules. Especially, organozincs have found many synthetic applications because of their
high functional group compatibility and their excellent reactivity in the presence of an appropriate
2
transition metal catalyst. Recently, we have found that an iodine–magnesium or a bromine–magnesium
exchange allows the preparation of polyfunctional aryl- or heteroaryl-magnesium halides bearing func-
3
tional groups like an ester, nitrile or a halogen. In the course of this study, we have observed that alkenyl
halides (bromides or iodides) are reluctant for undergoing an exchange reaction and that only alkenyl
iodides bearing an oxygen function which can subsequently stabilize the Grignard reagent, readily
undergo the I/Mg-exchange. Herein, we wish to report the dramatic effect of the presence of an electron-
withdrawing function attached at the α-position to the bromide on the rate of the Br/Mg-exchange. Thus,
4
5
6
functionalized alkenyl bromides like the bromonitriles 1 and 2 or the bromosulfone 3 are converted
under very mild conditions (i-PrMgBr (1.1 equiv.), THF, −45°C, 15–60 min) to the corresponding
organomagnesium derivatives 4–6 which react with various electrophiles leading to products of type
7–9 (Scheme 1 and Table 1).
Thus, the reaction of the functionalized alkenylmagnesium derivative 4 with allyl bromide in the
7
presence of CuCN (10% mol) furnishes the desired allylated product 7a in 77% yield as a E:Z
mixture of 90:10 (entry 1 of Table 1). The reaction of 4 with benzaldehyde gives the allylic alcohol
7b (E:Z=92:8, 65%, entry 2). After a transmetalation of 4 with CuCN·2LiCl, a benzoylation with
∗
Corresponding author.
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00387-7
tetl 16667

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320
Scheme 1.
PhCOCl affords the unsaturated ketonitrile 7c (E:Z=60:40) in 63% yield (entry 3). The addition of 4 to 4-
methoxyacetophenone or to crotonaldehyde furnishes, respectively, the allylic alcohol 7d (E:Z=70:30,
53%, entry 4) and the dienic alcohol 7e (E:Z=1:1, 47%, entry 5). In order to avoid the formation
of an E:Z mixture, the symmetrically β-disubstituted unsaturated bromonitrile 2 was used. The cor-
responding organomagnesium compound 5 is smoothly prepared (i-PrMgBr (1.1 equiv.), −40°C, 15
min) and the reaction of various electrophiles as described above (allylic bromides, aldehydes, acid
chlorides) proceeds well. Interestingly, the quenching of 5 with Me SiCl or Bu SnCl provides the α-
3
3
silylated and α-stannylated unsaturated nitriles 8c (93%) and 8d (48%, entries 8 and 9 of Table 1). A
phenylsulfonyl group is also an excellent electron-withdrawing group which considerably facilitates the
bromine–magnesium exchange. Thus, the bromosulfone 3 reacts at –45°C within 1 h with i-PrMgBr
leading to the desired organomagnesium species 6. Its reaction with typical electrophiles such as allyl
bromide, chlorotrimethylsilane, benzoyl chloride and benzaldehyde proceeds under the same conditions
as described above providing the functionalized sulfones 9a–d (62–82%) as pure E-isomers (entries
1
4–17 of Table 1). In order to determine the exact structure of the magnesium species 4 (magnesium
8
,9
13
attached to carbon or to nitrogen), we have recorded a C NMR spectra of the organomagnesium
intermediate 5 in THF-d at –35°C. We have observed a chemical shift of 129.6 ppm for CN which
8
is very close to the chemical shift of the CN of the starting material (115.9 ppm) indicating that the
magnesium may be attached to carbon and not to nitrogen. Interestingly, the α-silylated unsaturated
nitrile 8c has a chemical shift of 125.3 ppm (entry 8).
In summary, we have found that adjacent electron-withdrawing groups such as a cyano or phenyl-
sulfonyl group greatly facilitate the bromine–magnesium exchange allowing the preparation of novel
functionalized alkenylmagnesium reagents. Extention of this method is currently underway in our
1
0
laboratories.
Acknowledgements
We thank the DFG (Leibniz-Program) and the Fonds der Chemischen Industrie for generous financial
support. We thank BASF AG (Ludwigshafen), Chemetall GmbH (Frankfurt) and PPG-Sipsy SA (Avrillé,
France) for the generous gift of chemicals.

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321
Table 1
Products of type 7–9 obtained by the reaction of the functionalized Grignard reagents 4–6 via a
bromine–magnesium exchange

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322
References
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2
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10. Typical procedures. (a) Preparation of E-2-(1-hydroxy-2-propenyl)-3-propyl-2-hexenenitrile (8f, entry 11 of Table 1). A
dry three-necked flask equipped with a magnetic stirring bar and a septum was charged with the bromonitrile 2 (800 mg,
3
.7 mmol) in THF (25 mL). The reaction mixture was cooled to −40°C and i-PrMgBr (5.1 mL, 4.1 mmol, 0.8 M in THF)
was added dropwise. After 15 min of stirring at −40°C, crotonaldehyde (400 µL, 4.8 mmol) was added and the reaction
mixture was allowed to warm to rt. After 1 h, the reaction mixture was worked up as usual and the residue was purified
by flash-chromatography (pentane:ether, 75:25) yielding the dienic alcohol 8f (583 mg, 76% yield) as a colorless oil. (b)
Preparation of E-1-trimethylsilylethenylphenylsulfone (9b, entry 15 of Table 1). A dry three-necked flask equipped with
a magnetic stirring bar and a septum was charged with the bromosulfone 3 (500 mg, 1.55 mmol) in THF (10 mL). The
reaction mixture was cooled to −45°C and i-PrMgBr (2.1 mL, 1.7 mmol, 0.8 M in THF) was added dropwise and the
reaction mixture was stirred 1 h at −45°C. Me
3
SiCl (294 µL, 2.32 mmol) was added and the reaction mixture was allowed
to warm to rt and was stirred for 1 h. After the usual work up, the crude residue obtained after evaporation of the solvents
was purified by flash-chromatography (pentane:ether, 95:5) yielding the sulfone 9b (401 mg, 82% yield) as a white solid
(mp=82°C).