Synthesis of allyl ketone via Lewis acid promoted Barbier-type reaction

Article abstract of DOI:10.1016/S0040-4039(00)01446-5

A series of allyl ketones were synthesized from the mixture of zinc, nitrile and allyl bromide in the presence of AlCl₃ via Barbier-type reaction condition. When crotyl bromide was used for the allylation, only the γ-adduct was produced via the

Full text of DOI:10.1016/S0040-4039(00)01446-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8803–8806
Synthesis of allyl ketone via Lewis acid promoted
Barbier-type reaction
Adam Shih-Yuan Lee* and Li-Shin Lin
Department of Chemistry, Tamkang University, Tamsui 251, Taiwan
Received 27 July 2000; accepted 25 August 2000
Abstract
A series of allyl ketones were synthesized from the mixture of zinc, nitrile and allyl bromide in the
presence of AlCl3 via Barbier-type reaction condition. When crotyl bromide was used for the allylation,
only the g-adduct was produced via the SE2% pathway under the reaction condition. © 2000 Elsevier
Science Ltd. All rights reserved.
Since Blaise reported the addition of allylic iodide to nitrile, this potentially useful b,g-unsat-
urated ketone synthesis found little application in organic synthesis.1 Despite the notable
successes of allylation of carbonyl compounds,2,3 the condensation of allylic organometal
derivatives with nitriles for the direct synthesis of b,g-unsaturated ketones have usually to be
prepared indirectly by long and tedious methods and low yields are generally observed.4–6 Allyl
ketones have been prepared by the reactions of allyl organometallics of antimony,7 cadium,8
copper,9 indium,10 manganese,11 mercurry,12 nickle,13 rhodium,14 silicon,15,16 tin17,18 and zinc19
with acyl halides, but little functionality can be accommodated by these processes. Our previous
studies showed that b-amino-a,b-unsaturated ester was generated by a sonochemical Blaise
reaction condition.20,21 Therefore, we further investigated the allylation of allyl organometal
compounds (e.g. Bi, In, Li, Mg, Zn) with nitrile under the Barbier-type reaction condition.
Herewith, we wish to report an improvement in the Barbier-type allylation of nitrile in the
presence of Lewis acid which leads to the synthesis of allyl ketone after acidic quenching
(Scheme 1).
Scheme 1.
* Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01446-5

8804
The typical procedure for the synthesis of allyl ketone is as follows: aluminum trichloride (0.4
mmol) was added at once to a solution of zinc powder (4.0 mmol), nitrile (1.0 mmol) and allylic
bromide (1.5 mmol) in anhydrous THF (5 mL) at 0°C (ice-water bath).22 The reaction mixture
was warmed to room temperature and then stirred at room temperature. After the reaction was
completed (monitored by TLC), aqueous HCl (2 M, 5 mL) was added to the reaction mixture
and stirred at room temperature for 5 minutes. The reaction mixture was passed through a short
silica gel column and the organic solvent was removed directly under reduced pressure. Further
purification is achieved on a flash chromatograph with ethyl acetate/hexane as eluant. A series
of allyl ketones are synthesized under this typical reaction condition and the results are shown
in Table 1.
Table 1
Synthesis of allyl ketones
According to our previous studies for the activation of zinc by using ultrasound, we first
investigated the reaction of allylic bromide with benzylnitrile under sonochemical Barbier-type
reaction condition.20,21,23 No expected allyl ketones were generated under the ultrasonic reaction
condition. Thus, we investigated this sonochemical reaction condition in the presence of Lewis

8805
acid such as AlCl3, BiCl3 and CeCl3 for the activation of zinc and nitrile, but low yields were
achieved. Interestingly, the yield of allyl ketone was improved when allylic bromide was added to
a mixture of Zn, AlCl3 and nitrile in THF without ultrasound as activation source for zinc metal.
We also observed that the addition of Lewis acid to the mixture of zinc powder, nitrile and allylic
bromide in anhydrous THF increased dramatically the yield of allyl ketone. Many Lewis acids
such as TiCl4, ZrCl4, SnCl4, AlCl3, BiCl3, CeCl3, BF3 and ZnCl2 were investigated and the AlCl3
and ZrCl4 are the best Lewis acids for the allylation reaction with nitrile. Alkyl and aryl nitriles
were reacted with allylic bromide in the presence of AlCl3 to produce corresponding allyl ketones
with moderate to high yields under the reaction conditions.
Studies on the reactions of substituted allylmetals with carbonyl compounds were carried out
which focused on the regioselectivity of the allylic unit (SE2 or SE2%). Therefore, we further inves-
tigated the regioselectivity of the allylation reaction with nitrile under the reaction condition. A
mixture of zinc powder (4.0 equiv.), AlCl3 (0.4 equiv.), crotyl bromide (1.5 equiv.) and benzyl
nitrile (1.0 equiv.) in THF was investigated under the reaction condition and a 36% yield of 2-
methyl allyl ketone (g-adduct) was obtained after chromatography. We found that when the
crotyl bromide (1.5 equiv.) was added dropwise to a mixture of Zn powder (3.0 equiv.), AlCl3 (0.3
equiv.) and benzyl nitrile (1.0 equiv.) a higher yield (77%) was obtained. The lower amount of Zn
and AlCl3 and a different addition order of crotyl bromide improved the yield of 2-substituted
allyl ketone. A series of 2-methyl allyl ketones were synthesized under this reaction condition and
the results are shown in Table 2.
Table 2
Synthesis of 2-methyl allyl ketonesa

8806
In conclusion, this Lewis acid promoted Barbier-type reaction condition provides a simple
and facile method for the synthesis of allyl ketones. All nitriles and allylic bromides were used
directly without further purification when they were received. This procedure features in situ
activation of metal to generate allylmetal which reacted with nitrile to form allyl ketone after
acidic quenching. In addition, our investigations showed that numerous functionalities were also
inert to this reaction condition (e.g. bromide, ester, heterocyclic, etc.). These results led us to
expand this Lewis acid promoted Barbier-type reaction for synthesis of other biological
compounds.
Acknowledgements
We thank the National Science Council in Taiwan (NSC 89-2113-M-032-004) and Tamkang
University for financial support.
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