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This journal is c The Royal Society of Chemistry 2012 Chem. Soc. Rev., 2012, 41, 5641–5653 5641
Cite this: Chem. Soc. Rev., 2012, 41, 5641–5653
High-valent oxo-molybdenum and oxo-rhenium complexes as efficient
catalysts for X–H (X = Si, B, P and H) bond activation and for
organic reductions
Sara C. A. Sousa, Ivania Cabrita and Ana C. Fernandes*
Received 23rd April 2012
DOI: 10.1039/c2cs35155b
High-valent oxo-complexes have recently emerged as powerful catalysts for the activation
of X–H (X = Si, B, P and H) bonds and for the reduction of several functional groups.
This new reactivity represents a complete reversal from the traditional role of these complexes
as oxidation catalysts and opened a new research area for high-valent oxo-complexes.
This tutorial review highlights the work developed using high-valent oxo-molybdenum and
oxo-rhenium complexes as excellent catalysts for X–H (X = Si, B, P and H) bond activation and
for organic reductions.
1. Introduction
During many years, high-valent oxo-molybdenum1,2 and oxo-
rhenium3,4 complexes were employed as excellent catalysts for
oxidation reactions such as the oxidation of alkenes, sulfides,
and pyridines to the corresponding epoxides, sulfoxides and
pyridine N-oxides (Scheme 1).
As the active sites of several molybdoenzymes e.g. sulfite
oxidase, DMSO reductase and xanthine oxidase are formed
by a dioxo- or a monooxo-molybdenum unit, many oxo-
molybdenum complexes have been studied as chemical models
of their active sites.5–7
In recent years, several new developments into the chemistry
of high-valent oxo-complexes were reported. Among the most
interesting ones was the successful reduction of a variety of
functional groups promoted by oxo-complexes in high oxidation
states. In 2003, Toste and co-workers8 described a novel
method for the hydrosilylation of carbonyl compounds with
silanes catalyzed by the high-valent oxo-rhenium complex
ReIO2(PPh3)2 1, affording the corresponding silyl ethers in good
to excellent yields, with tolerance of a wide range of functional
groups (Scheme 2). This reaction provides an efficient and
practical one-step reduction-protection method of carbonyl
compounds. The use of high-valent oxo-complexes as catalysts
for organic reductions represents a complete reversal from the
traditional role of these complexes as oxidation catalysts.
Toste and co-workers9 have also proposed a catalytic cycle
(Scheme 3) for the hydrosilylation of carbonyl compounds,
Centro de Quımca Estrutural, Instituto Superior Tecnico,Av. Rovisco Pais, Lisbon 1049-001, Portugal.E-mail: [email protected]
Sara C. A. Sousa
Sara Sousa received her BSand MS degrees in Chemistryfrom the Faculty of Sciences,University of Lisbon, Portugal.Then, she obtained a Euro-master degree in Measure-ment Science in Chemistryfrom the University of Tartu,Estonia. In 2010, she startedher PhD work on the use of thehigh-valent oxo-complexes ascatalysts for organic reduc-tions at Centro de QuımicaEstrutural, Instituto SuperiorTecnico, Lisbon. Ivania Cabrita
Ivania Cabrita completed herMSc postgraduate degree inChemistry at the Universityof Lisbon, Portugal. She alsoobtained a Euromaster post-graduate degree in Measure-ment Science in Chemistryfrom the University of Tartu,Estonia. Recently, she joinedthe organic chemistry researchgroup as a PhD student atCentro de Quımica Estrutural,Instituto Superior Tecnico,Lisbon. Her research interestsinclude the synthesis and useof carbohydrates as scaffoldsfor asymmetric catalysis.
Chem Soc Rev Dynamic Article Links
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5642 Chem. Soc. Rev., 2012, 41, 5641–5653 This journal is c The Royal Society of Chemistry 2012
which involves the addition of a silane Si–H bond across one
of the rhenium-oxo bonds to form the siloxyrhenium hydride
intermediate 4, that reacts with a carbonyl substrate to
generate siloxyrhenium alkoxide 5, which in turn, affords the
silyl ether product.
This proposed mechanism was supported by DFT calcula-
tions performed by Wu and co-workers.10 The formation of
the hydride 4 demonstrated for the first time that the oxo-
rhenium complex ReIO2(PPh3)2 1 activates the Si–H bond of
the silane. The results reported by Toste8,9 opened a new
research area for high-valent oxo-complexes as catalysts for
Si–H bond activation and for organic reductions.
High-valent oxo-molybdenum complexes have also been
used as efficient catalysts for C–X bond forming reactions,
including carbon–carbon and carbon–heteroatom bonds.11
2. Si–H bond activation
2.1 Organic reductions using the catalytic system silane/
high-valent oxo-molybdenum complexes
2.1.1 Hydrosilylation of carbonyl compounds. After the
discovery of Toste8,9 that demonstrated the ability of the
high-valent oxo-rhenium complex ReIO2(PPh3)2 to activate
the Si–H bond of silanes and catalyze the hydrosilylation of
carbonyl compounds, Royo and co-workers12 investigated the
use of the dioxo-molybdenum complex MoO2Cl2 713 as
catalyst for the same reaction. The catalytic system silane/
MoO2Cl2 was investigated in the hydrosilylation of aldehydes
and ketones, affording the corresponding silyl ethers in
moderate to good yields (Scheme 4). The reaction is chemo-
selective, tolerating several functional groups such as –CF3,
–NO2, –Br, –CN and ester.
This is the first example of the reduction of carbonyl
compounds catalyzed by a high-valent oxo-molybdenum
complex, showing a complete reversal of the traditional role
of this catalyst.
Royo and co-workers14,15 have explored the catalytic
activity of other dioxo-molybdenum complexes such as
MoO2(S2CNEt2)2 10, MoO2(acac)2 11, CpMoO2Cl 12,
MoO2(mes)2 13, and the polymeric organotin-oxomolybdates
(R3Sn)2MoO4 14 and 15 in the hydrosilylation of aldehydes
and ketones (Scheme 5). The results obtained show that
complexes 11–15 catalyze these reactions but required heating
at 80 1C and longer reaction times compared to MoO2Cl2.
Compound 10 is inactive.
A mechanism for the hydrosilylation of aldehydes and ketones
catalyzed byMoO2Cl2 was proposed based onDFT calculations.16
Scheme 3 Proposed catalytic cycle for hydrosilylation of carbonyl
compounds.
Scheme 2 Hydrosilylation of carbonyl compounds catalyzed by 1.
Scheme 1 Oxidation reactions catalyzed by oxo-complexes.
Scheme 4 Hydrosilylation of carbonyl compounds catalyzed by
MoO2Cl2.
Ana C. Fernandes
Ana Fernandes graduated inChemistry at the Faculdadede Ciencias of the Universi-dade de Lisboa, Portugal(1991), where she receivedher PhD in Organic Chemistry(1996). Then, she workedas a Researcher at Herbex,Produtos Quımicos for twoyears in drug synthesis. From1999–2008 she held an Assis-tant Professor position atUniversidade Lusofona deHumanidades e Tecnologiasand in 2008 she became anAuxiliary Researcher at Insti-
tuto Superior Tecnico, Lisbon. Her research interests includedevelopment of novel methodologies for organic chemistrycatalyzed by high-valent oxo-complexes and use of carbo-hydrates as scaffolds for asymmetric catalysis and for thesynthesis of biologically important compounds.
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These studies demonstrated that the most favourable pathway
to the first step, the Si–H activation, is a [2+2] addition to the
MoQO bond, forming the hydride species MoCl2H(O)(OSiR3)
B (Scheme 6). However, the participation and concurrent
formation of B1 in the reaction, which corresponds to the
[3+2] addition of Si–H to MoO2Cl2, cannot be entirely ruled
out because its interconversion to B has lower activation
energy (33.2 kcal mol�1).
In the following step, the aldehyde approaches the hydride
species and coordinates weakly through the oxygen atom. Two
alternative pathways can be envisaged (Scheme 7): the classical
reduction, in which a hydrogen atom migrates to the carbon
atom to form an alkoxide, which then proceeds to generate the
final silyl ether, or a concerted mechanism involving the
migration of a hydrogen atom to a carbon and of a silyl ether
to an oxygen atom to generate the silyl ether weakly bounded
to the molybdenum atom. However, the authors did not rule
out the possibility of a radical mechanism for the hydrosilyla-
tion of aldehydes and ketones catalyzed by MoO2Cl2.
2.1.2 Reduction of imines. Fernandes and Romao investi-
gated the reduction of imines to the corresponding amines
with the catalytic system silane/MoO2Cl2 (10 mol%)
(Scheme 8).17 These reductions were explored with imines
bearing different functional groups e.g. –NO2, –CF3, –F,
–Cl, –CO2CH3, affording the amines in moderate to excellent
yields and good chemoselectivity.
2.1.3 Reduction of sulfoxides. The reduction (or deoxy-
genation) of sulfoxides to the corresponding sulfides is an
important organic and biological reaction. The catalytic system
PhSiH3/MoO2Cl2 was also tested in the reduction of sulfoxides
by Fernandes and Romao using 5 mol% of MoO2Cl2 and one
equivalent of phenylsilane in THF at reflux temperature under
an inert atmosphere (Scheme 9).18 This novel method is
suitable for the deoxygenation of aromatic and aliphatic
sulfoxides in excellent yields, with tolerance of other func-
tional groups such as halo, carboxyl, and vinyl.
2.1.4 Reduction of pyridine N-oxides. These authors18 have
also performed a brief investigation on the deoxygenation of
pyridine N-oxides by MoO2Cl2 7 and MoO2Cl2(H2O)2 2019
(Scheme 10). The substrates 3-picoline N-oxide and 4-picoline
N-oxide were reduced with the catalytic systems PhSiH3/
MoO2Cl2 and PhSiH3/MoO2Cl2(H2O)2 in good yields (83–85%),
demonstrating that these systems are also very efficient for the
deoxygenation of pyridine N-oxides.
2.1.5 Reduction of esters.The conversion of esters to the corre-
sponding alcohols is a fundamental process in organic synthesis.
Scheme 5 Hydrosilylation catalyzed by oxo-molybdenum complexes.
Scheme 6 Two pathways for Si–H addition to MoO2Cl2: [2+2]
addition to MoQO (above), [3+2] addition to MoQO (bottom).
Free energies are given in kcal mol�1.
Scheme 7 Free energy profile [kcal mol�1] for the concerted
reduction of aldehyde by [MoCl2(H)(O)(OSiH3)] (top), and classical
reduction followed by silyl migration (bottom).
Scheme 8 Reduction of imines catalyzed by MoO2Cl2.
Scheme 9 Reduction of sulfoxides catalyzed by MoO2Cl2.
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Fernandes and Romao have demonstrated that the catalytic
system PhSiH3/MoO2Cl2 (5 mol%) is very efficient for the
reduction of a variety of aliphatic and aromatic esters to the
corresponding alcohols in good yields (Scheme 11).20
The mechanism proposed for this reduction should involve
the formation of an alkyl silyl acetal, resulting from the
reaction between the ester and the hydride species (Mo–H),
which is easily converted into the corresponding aldehyde.
Then, the aldehyde reacts with a second equivalent of hydride
species (Mo–H) producing a silyl ether, followed by a rapid
hydrolysis to the alcohol.
2.1.6 Reduction of amides. The catalytic efficiency of the
system PhSiH3/MoO2Cl2 was also explored in the reduction of
amides to the corresponding amines (Scheme 12).21 Several
amides were reduced in moderate to good yields. This novel
methodology proved to be especially suitable for the reduction
of tertiary amides with bulky N-substituents.
2.1.7 Reductive amination of aldehydes. Direct reductive
amination is a powerful method for C–N bond formation and
for the synthesis of higher order amines from a carbonyl
compound and an amine. Smith and co-workers22 have devel-
oped an efficient method for direct reductive amination of
both electron-deficient and electron-rich aldehydes, using
MoO2Cl2 as catalyst and phenylsilane as the reducing agent
(Scheme 13). This method is environmentally friendly, using
ethanol or methanol as solvent in place of the standard
chlorinated solvents, and it is also chemoselective, tolerating
a number of reducible functional groups (e.g. –F, –Cl, –I,
–OMe, –NO2, –CO2Me, –CN) and heterocyclic ring systems.
2.1.8 Reduction of azides. Prabhu and co-workers23 have
developed a neutral and efficient strategy for the reduction
of azides to the corresponding amines catalyzed by
MoO2(S2CNEt2)2 10 in the presence of phenylsilane
(Scheme 14). This method tolerates a wide variety of reducible
functional groups e.g. chloro, nitro, cyano, aldehyde, ketone,
ester, amide, epoxide, alcohol, and double bonds.
2.2 Organic reductions using the catalytic system silane/
high-valent oxo-rhenium complexes
2.2.1 Hydrosilylation of carbonyl compounds. After the
initial studies developed by Toste8,9 about the hydrosilylation
of carbonyl compounds catalyzed by the oxo-rhenium
complex ReIO2(PPh3)2, Royo and co-workers24,25 explored
the catalytic activity of the oxo-rhenium complexes Re2O7 32,
CH3ReO3 (MTO) 33, ReOCl3(PPh3)2 34, and HReO4 35 in
the same reaction (Scheme 15). Among all the oxo-rhenium
Scheme 10 Reduction of pyridine N-oxides catalyzed by oxo-
molybdenum complexes.
Scheme 11 Reduction of esters catalyzed by MoO2Cl2.
Scheme 12 Reduction of amides catalyzed by MoO2Cl2.
Scheme 13 Reductive amination catalyzed by MoO2Cl2.
Scheme 15 Hydrosilylation catalyzed by oxo-rhenium complexes.
Scheme 14 Reduction of azides catalyzed by MoO2(S2CNEt2)2.
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complexes tested in the hydrosilylation of aldehydes, Re2O7
and HReO4 proved to be the most active catalysts, giving the
silyl ethers in good yields in few minutes.
These oxo-rhenium complexes were also tested in the hydro-
silylation of aromatic and aliphatic ketones (Scheme 15). In
contrast to the high reactivity of the complex Re2O7 in the
hydrosilylation of aldehydes, with ketones no product was
formed. MTO and ReOCl3(PPh3)2 were the most effective
catalysts for the hydrosilylation of ketones, producing the
corresponding silyl ethers in excellent yields.
At the same time, Abu-Omar and co-workers26–28 examined
the catalytic activity of other oxo-rhenium complexes such as
complexes 3826 and 3928 in the hydrosilylation of carbonyl
compounds (Scheme 16). Both the complexes proved to be
very efficient catalysts for the hydrosilylation of aromatic and
aliphatic aldehydes or ketones under mild, and open-flask
conditions.
2.2.2 Reduction of aromatic nitro compounds. The
reduction of aromatic nitro compounds to the corresponding
amines was also studied with silanes catalyzed by high-valent
oxo-rhenium complexes.29 The catalytic system PhMe2SiH/
ReIO2(PPh3)2 (5 mol%) reduced efficiently a series of aromatic
nitro compounds in the presence of a wide range of functional
groups e.g. ester, halo, amide, sulfone, lactone, and benzyl
(Scheme 17).
The mechanism proposed for the reduction of aromatic
nitro compounds with the system silane/oxo-rhenium com-
plexes initiates with the coordination of the nitro group to the
rhenium with liberation of the phosphines. Then, occurs the
addition of the silane to the complex containing the nitro
compound, forming a hydride species, followed by the reduction
of the nitro compound to the corresponding nitroso derivative
with liberation of R3SiOH. In the next two steps, the nitroso
intermediate is rapidly deoxygenated to the hydroxylamine,
which is then reduced to the amine by addition of two
equivalents of silane.
2.2.3 Reduction of alkenes. A novel method for the
reduction of alkenes to the corresponding alkanes with silanes
catalyzed by several oxo-rhenium complexes was developed by
Fernandes and co-workers.30 The catalytic system PhMe2SiH/
ReIO2(PPh3)2 (5 mol%) was tested in the reduction of a series
of styrene derivatives in excellent yields under solvent-free
conditions (Scheme 18). This catalytic system proved to be
also very efficient for the reduction of mono- and disubstituted
alkenes.
2.2.4 Reduction of sulfoxides. Fernandes and co-workers31,32
also tested several oxo-rhenium complexes in the reduction
of sulfoxides and found that the catalytic system PhSiH3/
ReIO2(PPh3)2 (1 mol%) was the most efficient for the
reduction of a wide range of aromatic and aliphatic sulfoxides
in excellent yields under mild conditions (Scheme 19). This
novel methodology is also highly chemoselective, tolerating
several functional groups such as –CHO, –CO2R, –Cl, –NO2,
and double or triple bonds.
2.2.5 Reduction of nitriles. The reduction of nitriles is a
powerful tool to synthesize primary amines and it is also
a fundamental process in organic chemistry. Cabrita and
Fernandes studied the reduction of nitriles to the corresponding
primary amines with silanes catalyzed by oxo-rhenium
complexes.33 The catalytic system PhSiH3/ReIO2(PPh3)2(10 mol%) reduced efficiently a variety of nitriles in the
presence of a wide range of functional groups (Scheme 20).
Furthermore, this novel methodology avoids the formation
of secondary amines, by unwanted side-reactions, which is a
general problem observed in the reduction of nitriles by
catalytic hydrogenation.
Scheme 16 Hydrosilylation of carbonyl compounds catalyzed by
catalysts 38 and 39.
Scheme 17 Reduction of aromatic nitro compounds catalyzed by
ReIO2(PPh3)2.
Scheme 18 Reduction of styrene derivatives catalyzed by ReIO2(PPh3)2.
Scheme 19 Reduction of sulfoxides with the system PhSiH3/
ReIO2(PPh3)2.
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The mechanism proposed for the reduction of nitriles with
the system silane/oxo-rhenium complexes involves the following
steps: coordination of two nitriles to the rhenium with libera-
tion of two phosphines, affording the complex ReIO2(nitrile)246; formation of the hydride species ðnitrileÞ2ðOÞIReðHÞOSiR0347 as a result of the addition of the Si–H bond of the silane to
one of the oxo-rhenium bonds; dihydrosilylation of the nitrile to
the corresponding N-disilylamine 52; and formation of amine
53 by hydrolysis ofN-disilylamine, probably due to the presence
of a trace of water in the reaction mixture (Scheme 21).
2.2.6 Reductive amination of aldehydes. The synthesis of
secondary and tertiary amines was explored by Sousa and
Fernandes through direct reductive amination of aldehydes
with silanes in the presence of a catalytic amount of oxo-
rhenium(V) and (VII) complexes (Scheme 22).34 The system
PhSiH3/ReIO2(PPh3)2 (2.5 mol%) proved to be the most
efficient and chemoselective for the synthesis of secondary
amines, tolerating a wide range of functional groups e.g.
–NO2, –CF3, –SO2R, –CO2R, –Cl, –Br, –CN, –OH, –OMe,
–NCOR, and double bonds.
This methodology was also employed in the synthesis of
tertiary amines, in moderate yields, reacting N-methylaniline
58 with several aldehydes using the system PhSiH3/
ReIO2(PPh3)2 (Scheme 23).
A plausible mechanism (Scheme 24) for the direct reductive
amination of aldehydes with the catalytic system PhSiH3/
ReIO2(PPh3)2 should initiate with the formation of the imine,
and coordination of this molecule to the catalyst by
substitution of the two phosphines, affording the complex
ReIO2(imine)2 60. In the second step, the hydride species
(imine)2(O)IRe(H)OSiR3 61 is formed as a result of the
addition of the Si–H bond of the silane to one of the oxo-
rhenium bonds. Then, the hydrosilylation of the imine occurs,
followed by hydrolysis to the corresponding amine 65. Finally,
the ReIO2(imine) 63 species formed will be stabilized by the
entry of another molecule of imine, regenerating the dioxo-
rhenium complex ReIO2(imine)2 60.
2.2.7 Asymmetric reductions catalyzed by oxo-rhenium
complexes. Toste and co-workers35,36 reported the synthesis
of a series of new chiral, non-racemic (CN-box)Re(V)-oxo
complexes 68, reacting ReOCl3(OPPh3)(SMe2) 66 with different
cyanobis(oxazoline) ligands 67 in dichloromethane at room
temperature (Scheme 25).
These catalysts were tested in the asymmetric hydrosilyla-
tion of ketones and imines (Scheme 26). The catalysts 71 and
72 reduced several aromatic, heteroaromatic and five-, six-,
and seven-membered cyclic ketones with good to excellent
enantioselectivity. In contrast, the reduction of non-aryl
ketones proceeded in good to excellent yields, but with modest
enantioenrichment of the resultant alcohols (6–15% ee).
Scheme 20 Reduction of nitriles catalyzed by ReIO2(PPh3)2
Scheme 21 Proposed mechanism for the reduction of nitriles.
Scheme 22 Synthesis of secondary amines catalyzed by ReIO2(PPh3)2.
Scheme 23 Synthesis of tertiary amines catalyzed by ReIO2(PPh3)2.
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The Re(V)-oxo catalyzed enantioselective hydrosilylation
of ketones was extended to the synthesis of chiral allylic
alcohols (Scheme 27). Modest enantioselectivities, 45–55% ee,
were obtained in the reaction with a,b-unsaturated conjugated
ketones and higher enantiomeric excesses, 55–63% ee, were
observed with a-substituted enone. The 1,4-reduction of the
enones was not observed under these conditions.
These authors also found that the in situ generation of chiral
catalyst 77, from complex 66 and ligand 76, provided the
synthesis of several allyl alcohols in moderate to good
enantiomeric excess by one-pot Meyer–Schuster rearrangement–
reduction of racemic propargyl alcohols 75 (Scheme 28).
Several allenyl alcohols were also subjected to the tandem
reaction conditions using the catalyst 71, generated in situ
from complex 66 and ligand 81, affording the corresponding
allylic alcohols in good yields (63–71%) and moderate to good
enantiomeric excess (56–77%) (Scheme 29).
The catalytic activity of the complex 72 was also examined in
the asymmetric reduction of phosphinyl imines (Scheme 30). The
results obtained demonstrated that acyclic and cyclic ketimines
were reduced in good yields with excellent enantioselectivity.
Scheme 24 Proposed mechanism for the reductive amination of
aldehydes.
Scheme 25 Synthesis of (CN-box)Re(V)-oxo complexes.
Scheme 26 Asymmetric hydrosilylation of ketones catalyzed by com-
plexes 71 and 72.
Scheme 27 Asymmetric reduction of enones catalyzed by complexes
71 and 72.
Scheme 28 TandemMeyer–Schuster rearrangement–hydrosilylation.
Scheme 29 Asymmetric synthesis of allylic alcohols catalyzed by 71.
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Similar selectivity was observed with heteroaromatic compounds.
In contrast, the reduction of aliphatic phosphinyl imines gave
low enantiomeric excess.
The synthesis of phenyl glycine derivatives was also
achieved through the reduction of the corresponding
a-imino esters catalyzed by oxo-rhenium complex 72 in
moderate to good yields with excellent enantioselectivity
(Scheme 31).
Finally, Toste and co-workers have also investigated the
synthesis of chiral allylic amines (Scheme 32) through the
chemo- and enantioselective reduction of the corresponding
imines. Conjugated aromatic imines were reduced in good
yields with excellent selectivity and unconjugated vinyl
imines were reduced with good enantioselectivity in moderate
yields.
3. B–H bond activation
The activation of the B–H bond of boranes with high-valent
oxo-molybdenum and oxo-rhenium complexes and the cata-
lytic activity of the system borane/high-valent oxo-complexes
in the reduction of sulfoxides were also investigated by
Fernandes and co-workers.32,37,38
3.1 Reduction of sulfoxides using the catalytic system borane/
high-valent oxo-molybdenum complexes
The study of the activation of the B–H bond of catecholborane
(HBcat) and borane (BH3�THF) by oxo-molybdenum com-
plexes was carried out in the reduction of sulfoxides.37 The
systems HBcat/MoO2Cl2(H2O)2 (5 mol%) and BH3�THF/
MoO2Cl2 (5 mol%) proved to be very efficient for the
deoxygenation of sulfoxides to the corresponding sulfides
(Scheme 33).
The reusability of MoO2Cl2(H2O)2 was evaluated and it was
observed that this catalyst can be reused in five catalytic cycles
with the same catalytic activity. This study represents the
first example of the B–H bond activation by high-valent
oxo-complexes and extends the role of MoO2Cl2 and
MoO2Cl2(H2O)2 as excellent catalysts for B–H bond
activation.
In order to understand the activation of the B–H bond of
boranes by the oxo-molybdenum complex MoO2Cl2(H2O)2,
Calhorda and Costa39 carried out a preliminary DFT study
showing that the [2+2] addition, with formation of a hydride,
is a feasible process (Scheme 34).
3.2 Reduction of sulfoxides using the catalytic system borane/
high-valent oxo-rhenium complexes
Fernandes and co-workers have also explored the reduction of
sulfoxides with the boranes HBcat, HBpin, and BH3�THF
catalyzed by the oxo-rhenium complexes ReIO2(PPh3)2,
ReOCl3(PPh3)2, ReOCl3(dppm), Re2O7, MTO, and HReO4.32,38
The catalytic systems HBcat/ReIO2(PPh3)2 (1 mol%), HBcat/
Re2O7 (1 mol%) and HBcat/MTO (1 mol%) were highly
efficient for the reduction of several sulfoxides at room temp-
erature under air atmosphere in few minutes (Scheme 35).
Scheme 30 Asymmetric reduction of phosphinyl imines catalyzed by 72.
Scheme 31 Asymmetric reduction of a-imino esters catalyzed by 72.
Scheme 32 Asymmetric synthesis of allylic amines catalyzed by oxo-
complex 72.
Scheme 33 Reduction of sulfoxides with the system borane/oxo-
molybdenum complexes.
Scheme 34 Activation of the B–H bond by MoO2Cl2(H2O)2.
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In order to study the activation of the B–H bond of boranes
by high-valent oxo-rhenium complexes Fernandes and
co-workers performed the reaction between the catecholborane
and the oxo-rhenium complex ReIO2(PPh3)2 in THF
at room temperature, obtaining the rhenium hydride
(PPh3)2(O)(I)Re(H)OBcat 88 in 50% yield (Scheme 36).40 A
similar reaction between pinacolborane (HBpin) and the oxo-
rhenium complex ReIO2(PPh3)2 gave a similar rhenium hydride,
(PPh3)2(O)(I)Re(H)OBpin 89, in 60% yield (Scheme 36).40 The
structural characterization by X-ray diffraction of 88 and 89
showed that these hydrides are formed by addition of the B–H
bond across the Re-oxo bond without dissociation of any
phosphine or substitution of the iodide ligand.
The synthesis of the novel hydrides 88 and 89 is a clear
demonstration that the high-valent oxo-rhenium complex
ReIO2(PPh3)2 activates the B–H bond of boranes. Usually,
the activation of boranes reported in the literature involves
transition metal complexes in a low oxidation state.41–43
A mechanism for the reduction of sulfoxides with the
catalytic system HBcat/ReIO2(PPh3)2 was also proposed
based on DFT calculations (Scheme 37). These studies
suggested that the reaction starts with the formation of
ReIO2(R2SO)2 90 by coordination of two molecules of sulf-
oxide to the rhenium with substitution of the two phosphines.
In the second step, the addition of the first molecule of HBcat
to yield the hydride ReHIO(R2SO)2(OBcat) 91 occurs,
followed by the loss of the sulfide, and oxidation of the metal
to the oxidation state VII. Then, a second HBcat molecule
attacks the Re(VII) intermediate, reducing the metal back to Re(V),
with release of H2 and BcatOBcat. Finally, occurs the coordi-
nation of a molecule of sulfoxide, regenerating the catalyst 90.
4. P–H bond activation
After the study of the activation of Si–H and B–H bonds by
oxo-molybdenum and oxo-rhenium complexes, the activation
of P–H bond was also investigated.
4.1 Hydrophosphonylation of aldehydes using the catalytic
system HP(O)(OEt)2/high-valent oxo-molybdenum complex
Fernandes and co-workers have reported the use of MoO2Cl2as a novel catalyst for P–H bond activation, exemplified by the
synthesis of a-hydroxyphosphonates and a-aminophospho-
nates obtained in the hydrophosphonylation of aldehydes44
and imines.45 The synthesis of a-hydroxy- and a-amino-
phosphonates has attracted much attention due to their important
biological activities as antibiotics,46 anti-tumor agents,47 and
enzyme inhibitors.48
A series of a-hydroxyphosphonates was prepared, in excellent
yields, using the catalytic system HP(O)(OEt)2/MoO2Cl2(5 mol%) under solvent-free conditions or at refluxing THF
(Scheme 38).
Scheme 35 Reduction of sulfoxides with the system boranes/oxo-
rhenium complexes.
Scheme 36 Synthesis of rhenium hydrides 88 and 89.
Scheme 37 Proposed mechanism for the reduction of sulfoxides.
Scheme 38 Hydrophosphonylation of aldehydes catalyzed byMoO2Cl2.
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This novel method proved to be very efficient and chemo-
selective, tolerating several functional groups e.g. –NO2, –CF3,
–F, –CN, –CO2Me, –OMe and double bonds.
To understand the activation of the P–H bond of
HP(O)(OMe)2 by MoO2Cl2 several computational studies
were carried out, which indicated that the activation occurs
with a [3+2] addition, starting with coordination of PQO to
molybdenum and hydrogen transfer from P–H to the oxo in
MoQO, forming Mo–OH (Scheme 39). In this case, [2+2]
addition with hydride formation is more unfavorable than the
[3+2] addition (Scheme 39).
Further computational studies were also performed for the
hydrophosphonylation of aldehydes catalyzed by MoO2Cl2(Scheme 40). The new intermediate O reacts with the aldehyde
substrate in two steps. In the first, the aldehyde binds to the
metal through the carbonyl, forming the C–P bond, and in
the second, the hydrogen is transferred from Mo–OH to the
oxygen of the final product.
4.2 Hydrophosphonylation of imines using the catalytic system
HP(O)(OEt)2/high-valent oxo-molybdenum complex
Fernandes and co-workers have also extended the use of
MoO2Cl2 as catalyst for the synthesis of a-aminophospho-
nates by addition of HP(O)(OEt)2 to imines (Scheme 41).45
This novel methodology was carried out under mild and
solvent-free conditions, with high yields, fast reaction times
and tolerance of several functional groups such as –CF3, –F,
–CN, –NO2, –OMe or a double bond conjugated to the
imino group.
This is the first example of the synthesis of a-hydroxy-and a-aminophosphonates catalyzed by a high-valent oxo-
molybdenum complex. This work opens a new research area
for high-valent oxo-molybdenum complexes as excellent
catalysts for C–P bond forming reactions.
5. H–H bond activation
In the last few years, the activation of H–H bond by high-
valent oxo-molybdenum and oxo-rhenium complexes was also
studied and the reactivity of the catalytic systemH2/oxo-complexes
was explored in different organic reductions.
5.1 Organic reduction using the catalytic system H2/high-
valent oxo-molybdenum and oxo-rhenium complexes
5.1.1 Reduction of alkynes. Royo and co-workers49 have
studied the addition of hydrogen to alkynes, affording the
corresponding alkenes, using the catalytic system H2/MoO2Cl2(Scheme 42). The reduction of 1-hexyne gave 1-hexene in 100%
yield. However, low or moderate yields were obtained in the
reduction of other alkynes.
This reaction was also studied with the oxo-rhenium
complexes MTO and ReIO2(PPh3)2 (Scheme 42).
Scheme 39 Two pathways for P–H addition to MoO2Cl2: [3+2]
addition (above), [2+2] addition (bottom) to MoQO. (DE0 top and
DG bottom in kcal mol�1).
Scheme 40 Reaction pathway for the reaction between the inter-
mediate O and the aldehyde substrate (DE0 top and DG bottom in
kcal mol�1).
Scheme 41 Hydrophosphonylation of imines catalyzed by MoO2Cl2.
Scheme 42 Reduction of alkynes catalyzed by oxo-complexes.
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Both complexes are catalytically active in the hydrogenation
of 1-hexyne, phenylacetylene and 3-hexyne, giving conversions
of 100, 70 and 47%, respectively, for MTO and 100% yield of
1-hexene for ReIO2(PPh3)2.
DFT computational studies showed that the mechanism for
dihydrogen activation by the Mo(VI) complexes starts with a
[2+2] addition of the H–H bond to the MoQO bond
(Scheme 43). The barrier is relatively high (57.8 kcal mol�1),
but the range of pressure and temperature required for the
catalytic conditions is consistent with it (typically 8 atm and 80 1C).
The hydride complex formed may then catalyze the reduction
of approaching substrates or it may undergo a reductive
elimination reaction, which leads to formation and later
elimination of water.
5.1.2 Reduction of sulfoxides. The deoxygenation of
methyl phenyl sulfoxide and dibutyl sulfoxide with hydrogen
in the presence of a catalytic amount of MoO2Cl2 or
MoO2(S2CNEt2)2 was also investigated by Royo and
co-workers.49 The reduction catalyzed by MoO2Cl2 gave the
sulfides in quantitative yields, but the reactions in the presence
of MoO2(S2CNEt2)2 afforded only low yields of the corres-
ponding sulfides (31–55%) (Scheme 44). In these reactions, the
oxygen of sulfoxides is removed as H2O. In the presence of the
oxo-rhenium complexes ReIO2(PPh3)2 and ReOCl3(PPh3)2,
this reduction afforded the corresponding sulfides in excellent
yields (Scheme 44).49
5.1.3 Reduction of aromatic nitro compounds. Royo and
Reis have also explored the reduction of aromatic nitro
compounds with H2 in the presence of a catalytic amount of
MoO2Cl2 in quantitative yields (Scheme 45).50 This method is
chemoselective, and it was successfully applied to the
reduction of several aromatic nitro compounds containing
carbonyl, cyano and halo groups or double bonds. The
reusability of the oxo-molybdenum complex was studied and
it was observed that MoO2Cl2 can be reused in three catalytic
cycles with the same catalytic activity.
5.1.4 Reduction of pyridineN-oxides. The same group further
extended the catalytic system H2/MoO2Cl2 (10 mol%) to the
reduction of several pyridine N-oxides, obtaining the corres-
ponding pyridines in quantitative yields, with tolerance of chloro,
cyano, aldehyde, and methoxy substituents (Scheme 46).50
5.1.5 Deoxygenation of epoxides and vicinal diols. Abu-
Omar and co-workers51 have reported a novel method for the
deoxygenation of epoxides and vicinal diols to the corres-
ponding alkenes using hydrogen as the reductant, at 150 1C
and 80–500 psi, catalyzed by MTO. This deoxygenation
method was found applicable to several aliphatic, aromatic,
and cyclic epoxides (Scheme 47). For example, 1-hexene oxide
afforded 1-hexene in 95% yield, styrene oxide gave styrene in
80% yield and cyclohexene oxide produced cyclohexene in 73%
yield. The only byproduct formed in this methodology is water.
This reaction was also tested in the deoxygenation of diols
(Scheme 48) and proved to be selective for the deoxygenation
of cis cyclic diols to the corresponding alkenes, signaling a
mechanism of extrusion from a coordinated epoxide via a
metallaoxetane intermediate (Scheme 49).
Scheme 43 Activation of the H–H bond by MoO2Cl2.
Scheme 44 Reduction of sulfoxides with the system H2/oxo-complexes.
Scheme 45 Reduction of aromatic nitro compounds with the system
H2/MoO2Cl2.
Scheme 46 Reduction of pyridineN-oxides with the systemH2/MoO2Cl2.
Scheme 47 Deoxygenation of epoxides catalyzed by MTO.
Scheme 48 Deoxygenation of diols catalyzed by MTO.
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6. Conclusion
This review gives an overview of the investigation in the X–H
(X = Si, B, P, and H) bond activation catalyzed by high-valent
oxo-molybdenum and oxo-rhenium complexes. The examples
compiled in this tutorial review clearly demonstrate the new role
of high-valent oxo-molybdenum and oxo-rhenium complexes as
excellent catalysts for X–H (X = Si, B, P, and H) bond
activation. Using these oxo-complexes as catalysts several
classes of functional groups such as aldehydes, ketones, esters,
amides, imines, sulfoxides, pyridine N-oxides, azides, alkenes,
and aromatic nitro compounds were easily reduced in an
efficient manner. These methodologies were also successfully
applied to the synthesis of secondary and tertiary amines by
reductive amination of aldehydes and for the preparation of
a-hydroxyphosphonates and a-aminophosphonates in excellent
yields. In many cases, these new methods provide milder
conditions and simpler procedures, tolerating several functional
groups, than previously reported methodologies.
The successful results obtained by Toste and co-workers in
asymmetric reductions of ketones and imines catalyzed by
oxo-rhenium complexes suggest that future use of these cata-
lysts will bring great benefits to both academia and industry
for the production of fine chemicals such as bioactive and
pharmaceutical compounds.
The activation of the X–H (X = Si, B, P, and H) bond is a
new and active area of research for high-valent oxo-complexes
that will certainly grow exponentially in the future providing
advantageous alternatives to existing catalysts. Future appli-
cations of these catalysts can include the activation of other
X–H bonds, hydrosilylation, hydroboration or hydrophos-
phonylation of alkenes, alkynes and imines, and new C–C
and C–heteroatom forming reactions.
Acknowledgements
This research was supported by FCT through projects PTDC/
QUI-QUI/110080/2009 and PTDC/QUI-QUI/110532/2009.
Sara C. A. Sousa and I. Cabrita thank FCT for grants
(SFRH/BD/63471/2009 and SFRH/BD/74280/2010).
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and vicinal diols.
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