Highly stereoselective semihydrogenation of alkynes promoted by nickel(0) nanoparticles

Article abstract of DOI:10.1002/adsc.200505327

A new method for the highly stereoselective cis-semihydrogenation of internal alkynes is described based on in situ generated Ni(0) nanoparticles and molecular hydrogen. This reduction system also allows the semihydrogenation of terminal alkynes.

Full text of DOI:10.1002/adsc.200505327

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DOI: 10.1002/adsc.200505327
Highly Stereoselective Semihydrogenation of Alkynes Promoted
by Nickel(0) Nanoparticles
˜
Francisco Alonso*, Inaki Osante, Miguel Yus*
´
´
Departamento de Química Organica, Facultad de Ciencias, and Instituto de Síntesis Organica (ISO),
Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain
Fax: (þ34)-96-590-3549, e-mail: yus@ua.es
Received: August 23, 2005; Accepted: November 17, 2005
Abstract: A new method for the highly stereoselec-
tive cis-semihydrogenation of internal alkynes is de-
scribed based on in situ generated Ni(0) nanoparti-
cles and molecular hydrogen. This reduction system
also allows the semihydrogenation of terminal al-
kynes.
of Lindlarꢀs catalyst[12] are noteworthy. At any rate,
most of the above-mentioned methods are not general
but are rather applied to a specific type of substrate.
Therefore, any new and efficient method for the semihy-
drogenation of alkynes is welcome.
In the recent years we have applied the system com-
posed of NiCl2 ·2 H2O-Li-arene(cat.) to the reduction
of a wide range of functional groups.[13] As regards the
reduction of alkynes, a variety of substrates could be
completely reduced to the corresponding alkanes,
whereas the semihydrogenation reaction could be only
controlled in a few cases without a general product ster-
eochemistry.[14] On the other hand, we have recently dis-
Keywords: (Z)-alkenes; alkynes; cis-hydrogenation;
nanoparticles; nickel; stereoselectivity
The semihydrogenation of the carbon-carbon triple covered that very fine nickel(0) nanoparticles with di-
bond is a particularly valuable reaction in synthetic or- ameters of 2.5Æ1.5 nm can be prepared by reduction
ganic chemistry. The difficulty to control the stereo- of anhydrous nickel(II) chloride with lithium powder
chemistry and to minimise the formation of over-re- and a catalytic amount of DTBB (4,4’-di-tert-butylbi-
duced products make it a challenging transformation. phenyl) in THF at room temperature.[15]
In the last decades, different general methods have
We report herein a new and efficient methodology for
been developed for this purpose and applied depending the stereoselective cis-semihydrogenation of alkynes,
on the stereochemistry desired for the final product, in- under the promotion of highly reactive nickel(0) nano-
cluding: (a) heterogeneous catalytic hydrogenation,[1] particles generated from the reducing system NiCl2-Li-
(b) homogeneous catalytic hydrogenation,[2] and (c) DTBB(cat.)-ROH. This methodology has also found
non-catalytic chemical methods[3a] (e.g., reduction by application in the semihydrogenation of terminal al-
diimide,[3b] dissolving metals,[3c, d] low-valent metal spe- kynes.
cies,[3e] hydroalumination,[3f] or metal hydride-transition
metal halide combinations[3g]).
The roles of the different components of the reducing
system mentioned above are as follows: (a) nickel(II)
Concerning the cis semireduction of alkynes and that chloride is the source of Ni(0) nanoparticles, (b) lithium
of terminal alkynes, Lindlar catalyst,[4] trialkylammoni- has a double role, the reduction of Ni(II) to Ni(0) and
um formates under palladium catalysis,[5] complex re- the in situ generation of molecular hydrogen by reaction
ducing agents of the type NaH-NaOR-MXn,[6] and dis- with the alcohol, (c) DTBB is used in catalytic amounts
persed nickel on graphite,[7] are some of the formerly uti- and acts as an electron carrier from lithium to nickel(II)
lised reducing systems, but they do not always lead to an
optimum selectivity. In fact, partial isomerisation of the
(Z)-alkene to the (E)-alkene, shift of the double bond,
over-reduction to the alkane, and problems with repro-
ducibilitywereobserved, especially with the Lindlar cat-
alyst. In the more recent literature, the higher selectivi-
ties achieved with a montmorillonite-supported com-
plex,[8] nickel boride or palladium catalysts on borohy-
dride exchange resin,[9] a homogeneous palladium(0)
catalyst,[10] palladium on pumice,[11] or using a variant Scheme 1.
Adv. Synth. Catal. 2006, 348, 305 – 308
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Table 1. Selective semihydrogenation of internal and terminal alkynes.
[a]
Reaction carried out at room temperature with EtOH as the hydrogen source, unless otherwise stated.
Conversion determined by analytical GLC.
Isolated yield of the olefin after column chromatography [silica gel (entries 1–10 and 14–18) or neutral alumina (entries
11–13), hexane or hexane/EtOAc], unless otherwise stated. For conversions lower than 100% the corresponding yield re-
fers to the amount of starting material converted.
[b]
[c]
[d]
[e]
[f]
Yield determined using analytical GLC and n-dodecane as an internal standard.
Z/E¼93: 7.
Reaction performed at 08C.
[g]
i-PrOH was used as the hydrogen source.
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Highly Stereoselective Semihydrogenation of Alkynes
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ethylaminoalkynes (entries 11–13) were prepared following
literature procedures of L. Brandsma [Synthesis of Acetylenes,
Allenes and Cumulenes: Methods and Techniques, Elsevier,
2004, pp. 215 and 2708, respectively].
chloride, and (d) ROH is the source of hydrogen, the
most effective alcohols being EtOH for internal alkynes
and i-PrOH for terminal alkynes. One of the main ad-
vantages of this methodology is that the handling of ex-
ternal molecular hydrogen is avoided since it is generat-
ed in situ in the reaction flask.
General Procedure for the Semihydrogenation of
Alkynes
The reducing system was applied to a wide range of in-
ternal and terminal alkynes with a high selectivity and
under very mild reaction conditions (Scheme 1 and Ta-
ble 1). Concerning the semihydrogenationof internal al-
kynes (Table 1), symmetrical dialkyl-substituted al-
kynes (entries 1 and 2) as well as cyclooctyne (entry 3)
were reduced to the corresponding alkenes with excel-
lent conversions and yields and with exclusive cis-ster-
eochemistry. Several hydroxyalkyl-substituted internal
alkynes were also successfully converted into the corre-
sponding cis olefins (entries 4–6). It is noteworthy that
even the more labile and isomerisation-prone oct-2-
en-1-ol was obtained in a 93:7 Z/E diastereomeric ratio
without any trace of the isomerised by-product octanal
(entry 6). Alkynes bearing an alkoxy moiety (entries
8–10) were nicely semireduced, the reaction conditions
being compatible with the presence of the benzyloxy
group, which did not undergo hydrogenolysis. Further-
more, several propargylic amines could be also trans-
formed into the corresponding cis allylic amines with
high conversions and isolated yields (entries 11–13).
The above methodology also found application in the
generally less studied and more difficult to control semi-
Anhydrous NiCl2 (130 mg, 1 mmol) was added to a preformed
blue suspension of lithium powder (28 mg, 4 mmol) and DTBB
(13 mg, 0.05 mmol, 2.5 mol %) in THF (5 mL) at room temper-
ature. The resulting mixture was stirred until formation of a
black suspension (ca. 10 min), thus indicating the formation
of Ni(0) nanoparticles. The reaction mixture was diluted with
THF (15 mL), followed by the addition of EtOH (0.12 mL,
2 mmol) or i-PrOH (0.15 mL, 2 mmol) and the alkyne
(1 mmol). Filtration through a pad containing silica gel and cel-
ite (ca. 3:1), followed by drying with anhydrous Na2SO4, and
solvent removal under vacuum (15 Torr), provided a crude re-
action product that was purified by column chromatography
(silica gel or neutral alumina, hexane or hexane/EtOAc, see
footnote[c] in Table 1).
Acknowledgements
This work was generously supported by the Spanish Ministerio
´
de Educacion y Ciencia (MEC; grant no. CTQ2004-01261) and
the Generalitat Valenciana (GV; grant nos. GRUPOS03/135
and GV05/005). I. O. thanks the Basque Country Government
hydrogenation ofterminalalkynes. Thus, avariety of ter- for a postdoctoral fellowship.
minal alkynes bearing alkyl, alkoxyalkyl, and arylami-
noalkyl substituents were reduced to the corresponding
terminal alkenes in good yields albeit with variable
amounts of the over-reduced alkanes (10–15%) (entries
References and Notes
14–18). It is worthy of note that also in this case the ben-
zyloxy group remained untouched under the reaction
conditions (entry 16).
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In summary, a new, mild and simple methodology for
the efficient stereoselective semihydrogenation of al-
kynes has been developed based on both in situ generat-
ed Ni(0) nanoparticles and hydrogen. Further research
on the application of the herein reported reducing sys-
tem to the selective reduction of olefins and dienes is un-
der way. The use of a polymer-supported arene as elec-
tron carrier as well as a version of the reaction involving
substoichiometric amounts of Ni(0) are also under
study.
Experimental Section
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