Barbier-type reactions of nitriles and alkyl iodides mediated by samarium(II) iodide in the presence of catalytic nickel(II) iodide

Article abstract of DOI:10.1016/S0040-4039(99)02194-2

The samarium(II) iodide-mediated intermolecular Barbier-type reactions of nitriles and alkyl iodides have been investigated. In the presence of a catalytic amount of nickel(II) iodide, the reaction proceeded smoothly to provide the corresponding ketones. Amides also reacted to give ketones under the same Barbier-type conditions. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(99)02194-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 937–939
Barbier-type reactions of nitriles and alkyl iodides mediated by
samarium(II) iodide in the presence of catalytic nickel(II) iodide
∗
Han-Young Kang and Sang-Eun Song
Department of Chemistry, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea
Received 29 September 1999; accepted 19 November 1999
Abstract
The samarium(II) iodide-mediated intermolecular Barbier-type reactions of nitriles and alkyl iodides have been
investigated. In the presence of a catalytic amount of nickel(II) iodide, the reaction proceeded smoothly to provide
the corresponding ketones. Amides also reacted to give ketones under the same Barbier-type conditions. © 2000
Elsevier Science Ltd. All rights reserved.
Keywords: samarium(II) iodide; Barbier reaction; nickel(II) iodides; nitriles; amides.
Samarium(II) iodide has been recognized as a versatile reagent in synthetic organic chemistry. The
reactivity of this useful reagent has been exploited in a variety of ways. As a result, it has been accepted
that functional groups such as esters, amides, or nitriles are tolerated in the normal reaction conditions
under which THF is employed as a solvent. It is also known that the reactivity of samarium(II) iodide
can be modified in the presence of suitable additives. Addition of metal salts as additives can modify
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the reactivity of this valuable reagent. Among various metal salts, nickel(II) iodide has been shown to
strongly increase the reactivity of samarium(II) iodide. Thus, the Kagan group has reported that in the
presence of nickel(II) iodide, samarium(II) iodide promotes the intermolecular Barbier reaction between
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alkyl iodides and esters. This reaction condition has been further applied to anhydrides. This discovery
inspired us to investigate the application of the SmI /NiI system to other functionalities.
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Nitriles have been one of the most useful functionalities in organic chemistry. This group is stable
under the usual conditions for samarium(II) iodide reactions (that is, THF as a solvent with or wi-
thout the addition of HMPA). A literature survey revealed only a few reports on the intramolecular
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reaction between ketones and nitriles. Molander and co-workers have reported only one example of
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the intramolecular Barbier-type reaction between alkyl iodides and nitriles, in which they needed to
add triphenylpiperidinophosphine oxide to achieve modest yields. No systematic studies on the Barbier-
type reaction between alkyl iodides and nitriles, especially no report of the intermolecular Barbier-type
reaction, has appeared. We wish to report our investigations of the intermolecular Barbier-type reaction
of nitriles and alkyl iodides mediated by samarium(II) iodide in the presence of catalytic nickel(II) iodide
(Eq. (1)).
∗
Corresponding author. E-mail: hykang@cbucc.chungbuk.ac.kr (H.-Y. Kang)
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02194-2
tetl 16122

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Table 1
Reaction of alkyl iodides with nitriles under Barbier conditions mediated by SmI
2 2
/(cat.) NiI a
(1)
Samarium(II) iodide-promoted reactions of alkyl iodides with nitriles in the presence of nickel(II)
iodide (catalytic amount) proceeded smoothly. Among the additives tested, NiI (catalytic amount)
2
6
provided the best results. Fe(DBM) also gave the ketones, albeit in lower yields. We also found that the
3
addition of HMPA alone did not provide the desired products. The results of the Barbier-type reactions of
7
nitriles with alkyl iodides by SmI /NiI (cat.) are summarized in Table 1. Benzonitrile and alkyl nitriles
2
2
reacted to give the desired ketones in moderate yields (entries 1–4). The reactions were performed at
°C and usually completed in 30 min. At temperatures lower than 0°C no reaction or only slow reactions
0
were observed. In the absence of additives no reaction occurred even when heated to reflux. More than
two equiv. of samarium(II) iodide in THF were used to complete most of the reactions. Acetonitrile
also provided the expected ketone when reacted with 3-phenylpropyl iodide although the yield was not
high (entry 9). Compounds having two cyano groups have also been tested (entries 5 and 6). Both 1,4-
dicyanobenzene and 1,3-dicyanobenzene gave the corresponding ketones as the major products with
one nitrile group remaining intact. In these cases, the corresponding diketones were produced in minor
amounts. Reacting adiponitrile with 3-phenylpropyl iodide offered the ketone, in which only one cyano
group reacted, as the major product (entry 7). For these dicyano-substituted compounds, more than four

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equiv. of samarium(II) iodide were employed to obtain reasonable yields. α,β-Unsaturated nitriles also
gave the ketones, albeit in lower yield (entry 8). 4-Pentenyl iodide also reacted with nitriles to provide
the expected ketones (entries 10 and 11).
After confirming the improved reactivity of samarium(II) iodide in the presence of nickel(II) iodide,
we briefly investigated the reaction of amides and alkyl iodides under this condition. Amides also reacted
to give the corresponding ketones. The results are shown in Table 2. More samarium(II) iodide (>4 equiv.)
was required to complete the reactions with yields usually lower than those obtained from nitriles.
Table 2
Reaction of alkyl iodides with amides under Barbier conditions mediated by SmI
2 2
/(cat.) NiI a
In summary, we have found that the reactivity of samarium(II) iodide is improved in the presence of
a catalytic amount of nickel(II) iodide. Successful intermolecular Barbier-type reactions of both nitriles
and amides with alkyl iodides were achieved under this condition. This new method for the preparation
of ketones, based on the enhanced reactivity of samarium(II) iodide, from nitriles or amides under mild
conditions should have an important synthetic utility.
Acknowledgements
We thank the Korea Science and Engineering Foundation for support (98-0501-04-01-3) of this
research.
References
1. (a) Kagan, H. B.; Namy, J.-L. In Lanthanides: Chemistry and Use in Organic Synthesis; Kobayashi, S., Ed.; Springer, 1999;
pp. 156–198. (b) Krief, A.; Laval, A.-M. Chem. Rev. 1999, 99, 745–777.
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. Machrohi, F.; Hamann, B.; Namy, J.-L.; Kagan, H. B. Synlett 1996, 633–634.
. Machrouchi, F.; Parlea, E.; Namy, J.-L. Eur. J. Org. Chem. 1998, 2431–2436.
. (a) Kraus, G.; Sy, J. O. J. Org. Chem. 1989, 54, 77–83. (b) Kraus, G. A.; Wan, Z. Tetrahedron Lett. 1997, 37, 6509–6512.
. Molander, G. A.; McKie, J. A. J. Org. Chem. 1993, 58, 7216–7227.
. Molander, G. A.; McKie, J. A. J. Org. Chem. 1991, 56, 4112–4120.
2
. Typical procedure: Preparation of phenyl propyl ketone. A catalytic amount (1%) of NiI was added to a solution of
samarium(II) iodide in THF (1.35 mmol). To this solution was added a solution of benzonitrile (51.6 mg, 0.5 mmol) and
iodopropane (170 mg, 1.0 mmol) in THF (4 mL) dropwise at 0°C. After stirring for 30 min at 0°C, the reaction mixture was
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quenched with Rochell’s salt solution. Extraction with dichloromethane, drying (MgSO
flash chromatography provided phenyl propyl ketone (50.4 mg, 68%).
. Schwaebe, M. K.; Little, R. D. Synth. Commun. 1997, 27, 837–840.
4
) and concentration followed by
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