Osmium catalyst for the borrowing hydrogen methodology: α-alkylation of arylacetonitriles and methyl ketones

Article abstract of DOI:10.1021/cs4005375

Complex [Os(η⁶-p-cymene)(OH)(IPr)]OTf is an efficient catalyst precursor for the α-alkylation of arylacetonitriles and methyl ketones with alcohols, which works with turnover frequencies between 675 and 176 h^-1 for nitriles and between 194 and 28 h^-1 for ketones.

Full text of DOI:10.1021/cs4005375

Letter
pubs.acs.org/acscatalysis
Osmium Catalyst for the Borrowing Hydrogen Methodology:
α‑Alkylation of Arylacetonitriles and Methyl Ketones
María L. Buil,† Miguel A. Esteruelas,†,* Juana Herrero,§ Susana Izquierdo,† Isidro M. Pastor,‡
and Miguel Yus‡,*
†Departamento de Química Inorgan
Zaragoza-CSIC, 50009 Zaragoza, Spain
§Departamento de Ingeniería Química y Química Inorgan
‡Departamento de Química Organ
ica, Facultad de Ciencias and Instituto de Síntesis Organ
́ ́ ́
ica, Instituto de Síntesis Química y Catalisis Homogenea (ISQCH), Universidad de
́
ica, ETSIIYT, Universidad de Cantabria, 39005 Santander, Spain
ica (ISO), Universidad de Alicante, Apdo.
́
́
99, 03080 Alicante, Spain
S
* Supporting Information
ABSTRACT: Complex [Os(η6-p-cymene)(OH)(IPr)]OTf is
an efficient catalyst precursor for the α-alkylation of
arylacetonitriles and methyl ketones with alcohols, which
works with turnover frequencies between 675 and 176 h−1 for
nitriles and between 194 and 28 h−1 for ketones.
KEYWORDS: osmium, borrowing hydrogen, hydrogen autotransfer, nitriles alkylation, ketones alkylation
he development of the borrowing hydrogen method-
ology,1 also called hydrogen autotransfer,2 is a challenge
In agreement with this, we reported the first osmium−N-
T
heterocyclic carbene (NHC) catalysts in 2005,14 [Os(η6-p-
cymene)Cl(CHPh)IPr]OTf and [Os(η6-p-cymene)Cl(
CHPh)IMes]OTf (IPr = 1,3-bis(2,6-diisopropylphenyl)-
imidazolylidene, IMes = 1,3-bis(2,4,6- trimethylphenyl)-
imidazolylidene; OTf = CF3SO3).15 They are active in the
ring-closing metathesis of diallyl diethylmalonate, the ring-
opening metathesis polymerization of cyclooctene, and a variety
of olefin cross-metatheses. Following this report, we sub-
sequently synthesized [Os(η6-p-cymene)(OH)IPr]OTf (1),
which was found to be an efficient catalyst precursor for the
hydrogen transfer reaction from 2-propanol to numerous
aromatic and aliphatic aldehydes16 and for the hydration of a
wide range of nitriles to amides.17 Now, we have observed that
this complex can be used in the borrowing hydrogen
methodology to promote the α-alkylation of arylacetonitriles
(eq 1) and methyl ketones, mainly acetophenone (eq 2).
for the modern chemistry from an economical and environ-
mental point of view, since it provides a useful alternative to
conventional alkylation reactions for the formation of C−C
bonds and the only waste generated through the overall process
is water. Catalysts temporarily remove hydrogen from an
alcohol substrate to provide an aldehyde or ketone
intermediate, which readily undergoes alkene formation. Return
of the hydrogen leads to an overall redox neutral process.
Key reactions involving C−C formation proceeding through
a borrowing hydrogen pathway include α-alkylation of nitriles
and ketones, the α-alkylation of nitriles being less studied. One
of the earliest examples using homogeneous catalysis involved
the Ru-promoted α-alkylation of aryl acetonitriles, reported by
Grigg and co-workers in 1981.3 Subsequently, this group4 and
Obora5 described the use of iridium catalysts.
Dialkylaminocyclopentadienylruthenium(II) complexes,6 Ru-
grafted hydrotalcite,7 and hydrotalcite-supported Pd nano-
particles7b have also been shown to be efficient. Although the
α-alkylation of ketones has been slightly more studied than that
of nitriles, the catalysts used are also based on few transition
metals: Ru,8 Ir,9 and Pd,10 as in the nitrile case. Here, we report
the first osmium catalyst, which is more efficient than those
previously studied, in particular for the α-alkylation of aryl
acetonitriles.
The alkylations of arylacetonitriles were performed in
toluene under reflux, using nitrile and alcohol concentrations
of 0.3 M and catalyst/substrate and KOH/substrate molar
Osmium has been traditionally used to prepare stable models
of reactive intermediates proposed in reactions catalyzed by
ruthenium analogous,11 whereas its use in catalysis has received
scarce attention.12 Recent findings have, however, demon-
strated that osmium is certainly a promising alternative to the
classical metal catalysts for promoting some organic reactions.13
Received: July 10, 2013
Revised: July 26, 2013
© XXXX American Chemical Society
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Letter
ratios of 1/100 and 1/5, respectively. Because complex 1 is also
a very efficient catalyst for the hydration of nitriles to amides,
the water generated during the process was removed from the
reaction medium by using a Dean−Stark receiver filled with
toluene. Under these conditions, the alkylation products are
obtained in high yield within a short time in all cases, with
turnover frequency values at 50% conversion (TOF50%), which
ranges from 675 to 176 h−1 (Table 1).
under microwave irradiation. Electron-donating substituents at
the para position of the aromatic ring of the nitrile slow down
the reaction (runs 2−4). In agreement with this, the TOF50%
values for the alkylation of 4-substituted phenylacetonitriles
decrease in the sequence H > Me > MeO; however, electron-
donating substituents at the para position of the phenyl group
of benzyl alcohol increase the alkylation rate. Thus, with (p-
methoxyphenyl)methanol, a TOF50% value of 675 h−1 is
reached (run 5). The position of the substituent of the
aromatic group of benzyl alcohol also has a clear influence on
the reaction rate, increasing it because the substituent is away
from the functional CH2OH (runs 6 and 7). According to this,
the TOF50% value for the alkylation of phenylacetonitrile with
m-tolylmethanol is higher than that for the reaction involving o-
tolylmethanol (493 vs 176 h−1). Less reactive aliphatic alcohols
are also efficient alkylation agents. Thus, the alkylation of
phenylacetonitrile with octan-1-ol takes place with a high
TOF50% value of 274 h−1 (run 8).
Table 1. α-Alkylation of Arylacetonitriles and Methyl
Ketones
Complex 1 is also the most efficient homogeneous catalyst
reported until now for the α-alkylation of acetophenone,
although the obtained TOF50% values, which range from 194 to
36 h−1, are significantly lower than those found for the reactions
with nitriles (Table 1). Under the conditions used for the latter,
the obtained ketones are formed in high yields after a few
hours, whereas more than 20 h is necessary to reach similar
yields with Ru, Ir, and Pd catalyst.8−10 In contrast to the α-
alkylation of phenylacetonitrile, electron-donating substituents
at the para position of the aromatic ring of benzyl alcohol slow
down the reaction (runs 9 and 10). Thus, the reaction with
benzyl alcohol (TOF50% = 194 h−1) is faster than that with p-
methoxybenzyl alcohol (TOF50% = 144 h−1). In this case, the
position of the substituent at the phenyl group of the alcohol
also has a marked influence on the rate and, similar to the α-
alkylation of phenylacetonitrile, it increases because the
substituent is away from the CH2OH group (runs 11 and
12). In accordance with this, the TOF50% value for the
alkylation with m-tolylmethanol (106 h−1) is higher than that
for the reaction with o-tolylmethanol (71 h−1). The alkylation
with the aliphatic octan-1-ol is also efficient (run 13), although
the TOF50% value of 36 h−1 is significantly lower. Complex 1
alkylates not only acetophenone but also aliphatic ketones.
Thus, the alkylation of 3,3-dimethylpentan-2-one with benzyl
alcohol takes place in high yield with a TOF50% of 28 h−1.
The hydroxo ligand of 1 is easily replaced by an alkoxide
group. In methanol at −30 °C, complex 1 evolves into the
methoxide derivative [(η6-p-cymene)Os(OCH3)(IPr)]OTf,
which has been isolated as a brown solid in high yield. The
isopropoxide counterpart is much less stable and rapidly leads
to the hydride−acetone derivative [Os(η6-p-cymene)OsH(κ1−
OC(CH3)2}(IPr)]OTf by means of a hydrogen β-elimination
reaction.16 In accordance with this, the α-alkylation of
arylnitriles can be rationalized according to Scheme 1. Under
the catalytic conditions, the hydroxo−alkoxide exchange should
afford 2, which should be the key species of the process. Thus, a
β-hydrogen elimination reaction on its alkoxide group could
give the hydride−aldehyde derivative 3. The subsequent
dissociation of the oxygen donor ligand should lead to the
unsaturated monohydride 4. Then the free aldehyde could
undergo a Knoevenagel condensation18 with the arylacetonitrile
to give water and an α,β-unsaturated nitrile, which should insert
into the Os−H bond of 4 to afford 5. Thus, the addition of the
O−H bond of a new alcohol molecule to the Os−C bond of 5
could finally yield the alkylation product and regenerate 2.
a
Reactions performed in toluene under Ar atmosphere at 110 °C using
3 mmol of the corresponding substrate (0.3 M). Os/substrate ratio:
0.01. KOH/substrate ratio: 0.2 using pentadecane as internal
reference. Turnover frequencies [(mol product/mol Os)/time]
were calculated at 50% conversion. Yields determined by H NMR
spectra.
b
c
1
The alkylation of phenylacetonitrile with benzyl alcohol in
the presence of 1 is significally faster than in the presence of the
iridium dimer [IrCp*Cl2]2, even when the latter is used under
microwave irradiation.4 Although the osmium catalyst works
with a TOF50% of 514 h−1 (run 1), the iridium system affords
only less than 2 h−1 under traditional heating and about 100 h−1
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Scheme 1. Proposed Mechanism for the Catalysis
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental and spectroscopy details for all the products. This
information is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: maester@unizar.es (M. A. E.), yus@ua.es (M.Y.).
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the Spanish MINECO [Projects
CTQ2007-65218/BQU, CTQ2011-23459, CTQ2011-24165,
and Consolider Ingenio 2010 (CSD2007-00006)], the DGA
(E35), Generalitat Valenciana (PROMETEO/2009/039 and
FEDER), and the European Social Fund (FSE) is acknowl-
edged. Dedicated to Prof. Antonio Laguna on the occasion of
his 65th birthday.
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