Angewandte
Chemie
DOI: 10.1002/anie.201306629
Iron Catalysis
Iron Pincer Complex Catalyzed, Environmentally Benign, E-Selective
Semi-Hydrogenation of Alkynes**
Dipankar Srimani, Yael Diskin-Posner, Yehoshoa Ben-David, and David Milstein*
Alkynes are useful building blocks in organic synthesis that
allow for a plethora of transformations. Among them, the
transition-metal catalyzed semi-hydrogenation of alkynes to
alkenes is a very important reaction in organic chemistry.[1] It
has been extensively used for the synthesis of biologically
important molecules, such as natural products, pharmaceut-
icals, and fragrances, because many of these molecules have
carbon–carbon double bonds with defined Z or E config-
urations.[2] Among the various catalytic (heterogeneous or
homogenous) and non-catalytic methods[1,3], hydrogenation
by using the Lindlar catalyst[4] is probably the most facile
procedure for obtaining Z-alkenes. The Z selectivity arises
from the addition of the two hydrogen atoms of H2 supra-
facially to the p system of the alkyne by a sequence of
hydrometalation/reductive elimination steps. However, the
analogous transformation of the alkyne functionality to the E-
alkene remains a major challenge, particularly in late-stage
synthesis. In fact, all commonly practiced methods for the
direct conversion of alkynes into E-alkenes are stoichiometric
in nature. The Birch-type reduction of alkynes by alkali
metals (Li, Na) in liquid ammonia is the traditional and
powerful method for the synthesis of E-alkenes,[5] but major
limitations are the low functional-group tolerance as a result
of the harsh reaction conditions, and the stoichiometric
amounts of waste generated. Although the use of over-
stoichiometric amounts of chromium reagents resulted in
some improvement in the scope of the E-selective hydro-
genation reaction,[6] the use of non-catalytic, toxic reagents,
and the generation of copious toxic waste are major problems.
In 1999, iridium-catalyzed selective hydrogenation of alkynes
to E-alkenes using methanol as the hydrogen donor was
described by Tani and co-workers.[7a] In 2002, Trost et al.
reported an effective two-step method for the synthesis of E-
alkenes, in which the alkyne is first subjected to a ruthenium-
catalyzed trans-hydrosilylation[7b] followed by proto-desilyla-
tion of the resulting alkenylsilanes with stoichiometric
amounts of a fluoride source. In 2005, Shirakawa et al.
demonstrated reduction of alkynes with hexamethyldisilane
and deuterium oxide to E-1,2-dideuterioalkenes.[7c] Cheng
and co-workers[7d] described an efficient palladium-catalyzed
reduction of alkynes by using HSiEt3 and H2O as the
hydrogen donors, with E-selectivity resulting from isomer-
ization of the nascent Z-alkene to the more stable E-alkene
by using a catalytic amount of CuSO4. Yin, Han et al.[7e]
reported that in their palladium-catalyzed hydrogen-transfer
reaction, changing the hydrogen donor from formic acid to
25% aqueous formic acid also led to the isomerization of Z-
to E-alkenes. Bargon and co-workers reported an NMR study
on ruthenium-catalyzed E-selective semi-hydrogenation that
excluded the possibility of Z–E isomerism and confirmed
direct E-hydrogenation, thus suggesting a bridged alkyne–
dihydrogen dinuclear ruthenium complex.[7f] Very recently,
Fꢀrstner and co-workers disclosed a catalytic method for
alkyne semi-hydrogenation using a mixture of [Cp*Ru-
(cod)Cl] (5.5 mol%) and AgOTf (5 mol%) with H2 (10 bar)
at ambient temperature, and this method produced excellent
E-selectivity.[7g]
The replacement of expensive noble-metal catalysts by
inexpensive and environmentally benign metals is a desirable
goal in chemistry. Iron complexes in particular would provide
an excellent alternative owing to the high natural abundance
and low toxicity of iron.[8] Recently, we[9] and several other
groups[10] have focused on developing homogeneous iron
catalysts as precious-metal surrogates. We recently reported
a highly efficient hydrogenation of ketones catalyzed by an
iron pincer complex in the presence of catalytic amounts of
base.[9a,c] A new mode of cooperation between the metal
center and the pincer ligand, which has also been observed for
the corresponding ruthenium complexes,[11] was suggested. In
the context of the iron-catalyzed reduction of alkynes to
alkenes, Plietker and Belger[12] presented a hydrosilylation–
desilylation strategy involving the use of a [FeH(CO)(NO)-
(Ph3P)2] catalyst to give alkenes with good stereo-selectivity,
and Beller and co-workers[13] reported a method for the iron-
catalyzed transfer hydrogenation of terminal alkynes to the
corresponding alkenes using formic acid as a hydrogen donor.
Of particular interest is the atom-economical semi-hydro-
genation of alkynes with H2 gas. Chirik and co-workers[14]
reported the hydrogenation of diphenylacetylene catalyzed
by a bis(imino)pyridine iron dinitrogen complex in a reaction
that initially resulted in the selective formation of Z-stilbene
followed by complete conversion into bibenzyl. An E-
selective catalytic semi-hydrogenation of internal alkynes
with an iron-catalyst is highly desirable, especially when
compatible with a diverse range of functional groups. Herein,
we present such a reaction, catalyzed by a novel acridine-
based PNP iron complex.
[*] Dr. D. Srimani, Y. Ben-David, Prof. Dr. D. Milstein
Department of Organic Chemistry, Weizmann Institute of Science
76100 Rehovot (Israel)
E-mail: david.milstein@weizmann.ac.il
Dr. Y. Diskin-Posner
Chemical Research Support, Weizmann Institute of Science
76100 Rehovot (Israel)
[**] This research was supported by the European Research Council
under the FP7 framework (ERC No 246837) and by the Israel
Science Foundation. D.M. holds the Israel Matz Professorial Chair
of Organic Chemistry.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2013, 52, 14131 –14134
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
14131