Transfer Hydrogenation of Aldehydes, Allylic Alcohols, Ketones, and Imines Using Molybdenum Cyclopentadienone Complexes

Article abstract of DOI:10.1021/acs.organomet.8b00086

The molybdenum tetraphenylcyclopentadienone complex (C₅Ph₄O)Mo(CO)₃(CH₃CN) 1a is an effective precatalyst for the transfer hydrogenation of aldehydes, allylic alcohols, ketones, and imines under mild conditions with either 2-propanol or formic acid as reducing reagent. Mechanistic studies suggest that these molybdenum cyclopentadienone complexes can be reduced to the corresponding hydroxycyclopentadienyl Mo hydrides. These complexes, by virtue of the hydroxyl group on the cyclopentadienyl ligand, are more reactive and chemoselective than the analogous cyclopentadienyl molybdenum complexes for the reduction of ketones, aldehydes, and imines.

Full text of DOI:10.1021/acs.organomet.8b00086

Article
Cite This: Organometallics XXXX, XXX, XXX−XXX
Transfer Hydrogenation of Aldehydes, Allylic Alcohols, Ketones, and
Imines Using Molybdenum Cyclopentadienone Complexes
Weiwei Wu, Tomohiro Seki, Katherine L. Walker, and Robert M. Waymouth*
Department of Chemistry, Stanford University, Stanford, California 94306, United States
S
* Supporting Information
ABSTRACT: The molybdenum tetraphenylcyclopentadienone complex (C5Ph4O)-
Mo(CO)3(CH3CN) 1a is an effective precatalyst for the transfer hydrogenation of
aldehydes, allylic alcohols, ketones, and imines under mild conditions with either
2-propanol or formic acid as reducing reagent. Mechanistic studies suggest that these
molybdenum cyclopentadienone complexes can be reduced to the corresponding
hydroxycyclopentadienyl Mo hydrides. These complexes, by virtue of the hydroxyl
group on the cyclopentadienyl ligand, are more reactive and chemoselective than the
analogous cyclopentadienyl molybdenum complexes for the reduction of ketones,
aldehydes, and imines.
Scheme 1. Catalytic Transfer Hydrogenation with Mo
Tetracyclone Complex 1a
INTRODUCTION
■
Transfer hydrogenation is a powerful and convenient method
for the hydrogenation of a wide variety of substrates.1−5
Dihydrogen donors such as 2-propanol and formic acid are
inexpensive and available in large scale from renewable energy
sources. Among various classes of transition metal transfer
hydrogenation catalysts, those that adopt metal−ligand bifunc-
tional mechanisms6,7 are particularly attractive due to their
exceptional reactivity, chemo- and enantioselectivity in transfer
hydrogenation, and asymmetric transfer hydrogenation of polar
bonds. Ruthenium tetraphenylcyclopentadienone (tetracyclone)
complexes, first developed by Shvo,4,8,9 represent a class of
metal−ligand bifunctional catalysts, where the transfer of sepa-
rate hydrogen atoms occurs from the metal center and the
hydroxyl group on the cyclopentadienyl ligand. Subsequently,
several other transition metal analogues have been reported
(Fe, Os, Co, Rh, Re, Ir, Ni);4,10−14 the Fe13 and Re14 analogues
were shown to be active transfer hydrogenation catalysts.
Herein, we report that the molybdenum tetraphenylcyclopen-
tadienone complex 1a15,16 functions as an efficient catalyst
precursor for the transfer hydrogenation of aldehydes, ketones,
and imines (Scheme 1). Mechanistic studies imply that these
molybdenum cyclopentadienone complexes can be reduced to
the corresponding hydroxycyclopentadienyl Mo hydrides.
These complexes, by virtue of the hydroxyl group on the
cyclopentadienyl ligand, are more reactive and chemoselective
than the analogous cyclopentadienyl molybdenum complexes.17−19
excess 2-propanol. Cinnamaldehyde was fully reduced to the
saturated alcohol, whereas, for a nonconjugated enal, the alde-
hyde was reduced selectively (entries 2, 3). Aldehydes were hydro-
genated much more rapidly than ketones (entries 1, 6, 10). In an
internal competition experiment with benzaldehyde and aceto-
phenone, 1a demonstrated 47:1 selectivity for benzaldehyde,
which is comparable to the original dimeric ruthenium Shvo
catalyst.20 Aldimines were reduced in higher yield than the
corresponding ketimines (entries 8, 9). The substituted
α,β-unsaturated alcohol was hydrogenated slightly less effi-
ciently than the unsubstituted allyl alcohol (entries 4, 5).
Molybdenum complex 1a also showed high chemoselectivity:
esters, amide, primary imines, and isolated alkenes and alkynes
are not hydrogenated. 2-Acetylpyridine was not hydrogenated
possibly due to the inhibition of the pyridine moiety binding to
the molybdenum center.
RESULT AND DISCUSSION
■
Formic acid can also serve as reducing agent for aldehydes,
ketones, and allylic alcohols, but not imines. The reaction rate
is comparable with 2-propanol as reducing reagent, and was
The synthesis of molybdenum complex 1a was carried out as
previously reported by Morris et al.15 Molybdenum complex 1a
was found to be an efficient and selective catalyst for hydro-
genation of polar multiple bonds of aldehydes, allylic alcohols,
ketones, and imines (Table 1). Benzaldehyde was hydrogenated
to benzyl alcohol (>99%) in 12 h at 65 °C in the presence of
Received: February 8, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.8b00086
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c
Table 1. Transfer Hydrogenation of Aldehydes, Allylic Alcohols, Ketones, and Imines Catalyzed by Molybdenum Complex 1a
a
b
For entries 3−5, formic acid (2.0 M) was used as reducing reagent for the ease of product isolation. NMR yields (isolated yields in parentheses).
c
Conditions: substrate (0.33 M), molybdenum precatalyst 1a (10.0 mol %), d6-benzene (0.4 mL), 2-propanol (2.0 M) at 65 °C.
adopted for entries 3, 4, and 5 for the ease of isolation of
volatile products. Molybdenum complex 1a is stable in the
presence of water, and the transfer hydrogenation reaction can
be run in air, but 1a has limited air stability in its solid state.
to the hydroxyl group on the cyclopentadienyl ligand could not
be identified in the H NMR spectrum of 1b, presumably as a
consequence of hydrogen bonding and exchange. After 12 h at
1
25 °C, the reaction of 1a with 2-propanol reaches equilibrium;
1
1
The kinetics was monitored by H NMR spectroscopy with
integration of the H NMR spectra yields an equilibrium con-
benzaldehyde as dihydrogen acceptor and 2-propanol as the
reducing agent. When the catalytic reaction of benzaldehyde
and 2-propanol was monitored at 65 °C by H NMR, both 1a
stant Keq = 0.98, as determined from a series of experiments at
different initial 2-propanol concentrations. Due to the reversible
nature of the reaction, attempts to isolate and fully characterize
1b were unsuccessful. Nevertheless, the identity of 1b could
be established by analysis of the reaction mixture of 1a and
2-propanol by 1H NMR and 13C NMR spectroscopy of and by
in operando high resolution mass spectrometry21,22 which
revealed an ion at m/z 591.0492, consistent with the sodium
adduct of 1b [(C5Ph4OH)Mo(H)(CO)3(Na)]+.
1
and a molybdenum hydride, formulated as (C5Ph4OH)Mo(H)-
(CO)3 1b (δ −3.92), could be identified in the reaction mixtures.
The rate of transfer hydrogenation was determined to be first-
order in 1a, 2-propanol, and benzaldehyde for [2-propanol]0 <
1.6 M. At higher concentrations of 2-propanol ([2-propanol]0 >
1.6 M), the rate is insensitive to 2-propanol concentrations,
indicative of saturation behavior (Figure S5, Supporting
Information). These data suggest that, at modest 2-propanol
concentrations, the turnover-limiting step is the formation of a
molybdenum hydride complex, formulated as 1b; whereas, in
the saturation regime, dihydrogen transfer from molybdenum
hydride 1b to benzaldehyde becomes turnover-limiting.
The pseudo-second-order rate constant for the catalytic process
at 65 °C was determined to be 3.4 × 10−3 M−1 s−1 when
[2-propanol]0 > 1.6 M.
Treatment of molybdenum complex 1a with excess formic
acid in benzene-d6 at 25 °C afforded a mixture of species char-
acterized as the protonated cationic molybdenum complex 2a
and the molybdenum formate complex 3 (eq 2). The molyb-
1
denum formate complex 3 was identified by H NMR and by
high resolution mass spectroscopy in negative mode as the
deprotonated anion (measured: m/z 611.0386; calcd: m/z
611.0389). The identity of 2a was corroborated by an indepen-
dent synthesis of the analogous air- and moisture-stable cationic
complex 2b (93% yield) from 1a and excess HBF4 in benzene
(eq 3; see the Supporting Information).
A series of stoichiometric experiments were carried out in an
effort to identify plausible reaction intermediates. Upon treat-
ment of Mo complex 1a with a stoichiometric amount of
1
2-propanol in benzene-d6 at 25 °C, analysis by H NMR spec-
troscopy revealed the slow formation of acetone (δ 1.55 ppm)
concomitant with that of a new hydride resonance at δ −3.88 ppm.
These data are consistent with the oxidation of 2-propanol to
acetone and the conversion of the Mo complex 1a to the molyb-
denum hydride complex 1b (eq 1). Resonances corresponding
The formate complex 3 and the cationic acetonitrile complex 2a
are in dynamic exchange in benzene-d6 at 25 °C. Upon mild
heating of the reaction mixture (65 °C), partial decarboxylation
B
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Scheme 2. Proposed Mechanism for Catalytic Transfer Hydrogenation with Mo Complex 1a
was observed to generate resonances consistent with the molyb-
denum hydride complex 1b (eq 2). Similar behavior was
observed for the analogous Ru formate complex.23
diphenylacetone to diphenylmethanol with a selectivity of 29%
in competition with decarboxylation and disproportionation.24
In contrast, complex 1a catalyzes the reduction of benzaldehyde
with excess formic acid with high selectivity (90% isolated yield
of benzyl alcohol; see the Supporting Information). We pro-
pose that the higher selectivity observed with Mo complex 1a is
due to the cooperative effect of the hydroxyl substituent on the
cyclopentadienyl ligand, as supported by the stoichiometric
investigations.
While 1a is more active than cyclopentadienyl Mo com-
plexes, it is less active than the corresponding Ru Shvo com-
plexes.4,20,25 Nevertheless, as observed for the Shvo-type com-
plexes,4,25 the Mo complex 1a catalyzes the reduction of carbonyl
complexes with formic acid as the reducing agent.26−40 Formic
acid is a convenient and inexpensive reducing agent; release
of CO2 as byproduct renders the reaction effectively irre-
versible.41−46 In addition, H2 gas can also be used, but it is less
effective than either 2-propanol or formic acid for the reduction
of benzaldehyde (see the Supporting Information, p S9).
Treatment of the molybdenum complex 1a with a stoichio-
metric amount of triethylsilane at room temperature generated
1
the molybdenum hydride species 4 (eq 4). H NMR spec-
troscopy showed upfield shifted resonances for the ethyl groups
at δ 0.70 and δ 0.23, and a molybdenum hydride resonance at
δ −4.20 ppm. This complex was isolated in 84% yield and char-
acterized by NMR and high-resolution mass spectroscopy as
the deprotonated anion of 4 in negative mode (measured: m/z
681.1358; calcd: m/z 681.1368).
The silylated Mo-H 4 was inactive for the catalytic transfer
hydrogenation of benzaldehyde with 2-propanol as the
dihydrogen source; no reaction was observed with complex 4
over 2 days. When transfer hydrogenation of benzaldehyde was
attempted with formic acid as the reducing agent, complex 4
decomposed to unknown products and no reduction was
observed for benzaldehyde. Similarly, the cationic complex 2b
did not exhibit catalytic activity for the transfer hydrogenation
of benzaldehyde with either 2-propanol or formic acid. The lack
of activity for either 2b or 4 suggests that both the free hydroxyl
group and hydride play an important role for the catalytic
transfer hydrogenation reactivity. These data are consistent
with a mechanism analogous to that proposed for the Shvo-
type transfer hydrogenation catalysts4 where both the O-H
of the hydroxycyclopentadienyl ligand and the Ru-H are
critical for mediating the reduction of carbonyl compounds
(Scheme 2).
The catalytic reactivity of Mo complex 1a can be contrasted
with that of related cyclopentadienyl complexes. The Mo pre-
catalyst 1a exhibits higher catalytic activity and chemoselec-
tivity for carbonyl reduction compared to those reported for
cyclopentadienyl molybdenum catalysts that do not contain a
hydroxycyclopentadienyl ligand.17−19 For cyclopentadienyl
molybdenum complexes (Cp′Mo(CO)3H, Cp′ = cyclopenta-
dienyl or substituted cyclopentadienyl ligand), hydrogenation
of carbonyl compounds was proposed to proceed by an ionic
mechanism involving oxidative addition of H2 to a cationic Mo
center to generate a cationic dihydride.17−19 Parkin24 demon-
strated that the related CpMo(PMe3)3−x(CO)xH complexes
catalyze dehydrogenation, disproportionation, and transfer
hydrogenation reactions of formic acid. In the presence of
formic acid, the CpMo(CO)3H complexes catalytically reduce
CONCLUSION
■
In summary, the molybdenum cyclopentadienone complex
1a15,16 is an efficient catalyst precursor for the transfer hydro-
genation of aldehydes, ketones, and imines. Mechanistic studies
reveal that these Mo complexes catalyze transfer hydrogenation
by a mechanism analogous to that of the Shvo-type complexes
of Ru, Re, and Fe.13,14 These studies reveal that the cooperative
behavior of redox- and proton-active tetracyclone ligands with
metal hydrides, as pioneered by Shvo,4,8,9 is a general strategy
for the design of bifunctional transfer hydrogenation catalysts.
Efforts to improve the stability and reactivity by modification of
the cyclopentadienone ligand are currently in progress.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.organomet.8b00086.
Experimental procedures, characterization data, and spectra
(PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: waymouth@stanford.edu.
■
ORCID
Weiwei Wu: 0000-0002-7951-3487
Katherine L. Walker: 0000-0002-7924-8185
Robert M. Waymouth: 0000-0001-9862-9509
C
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Notes
The authors declare no competing financial interest.
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Foundation (CHE-1565947). K.L.W. acknowledges the Center
for Molecular Analysis and Design (CMAD, Stanford) for a
fellowship and the National Science Foundation Graduate
Research Fellowship Program for support (GRFP).
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