Efficient and selective hydrogenation of amides to alcohols and amines using a well-defined manganese-PNN pincer complex

Article abstract of DOI:10.1039/c7sc00138j

Novel well-defined NNP and PNP manganese pincer complexes have been synthetized and fully characterized. The catalyst Mn-2 containing an imidazolyaminolphosphino ligand shows high activity and selectivity in the hydrogenation of a wide range of secondary and tertiary amides to the corresponding alcohols and amines, under relatively mild conditions. For the first time, more challenging substrates like primary aromatic amides including an actual herbicide can also be hydrogenated using this earth-abundant metal-based pincer catalyst.

Full text of DOI:10.1039/c7sc00138j

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Efficient and selective hydrogenation of amides to
alcohols and amines using a well-defined
manganese–PNN pincer complex†
Cite this: DOI: 10.1039/c7sc00138j
a
a
ab
Veronica Papa,‡ Jose R. Cabrero-Antonino,‡ Elisabetta Alberico,
a
a
a
a
Anke Spanneberg, Kathrin Junge, Henrik Junge and Matthias Beller*
Novel well-defined NNP and PNP manganese pincer complexes have been synthetized and fully
characterized. The catalyst Mn-2 containing an imidazolyaminolphosphino ligand shows high activity and
selectivity in the hydrogenation of a wide range of secondary and tertiary amides to the corresponding
alcohols and amines, under relatively mild conditions. For the first time, more challenging substrates like
primary aromatic amides including an actual herbicide can also be hydrogenated using this earth-
abundant metal-based pincer catalyst.
Received 11th January 2017
Accepted 24th February 2017
DOI: 10.1039/c7sc00138j
rsc.li/chemical-science
5
a,7
hemiaminal or related intermediates.
Here, two different
Introduction
pathways (C–O or C–N bond breaking, hydrogenation and
5
c
Reduction of carboxylic acid derivatives represents an impor- hydrogenolysis, respectively) can occur (Scheme 1). The C–O
tant process in organic synthesis with potential application in cleavage pathway forms the higher amine as the product with
1,2
both industrial and academic settings.
Traditionally, this reaction is performed using an excess of
3
reducing agents producing stoichiometric amounts of waste-
4
products. In contrast, catalytic hydrogenation using molecular
hydrogen is a much more atom-economical and waste-free
4c,5
approach. Unfortunately, amides constitute one of the least
reactive derivatives among all classes of carbonyl compounds
because of the low electrophilicity of the carbonyl group. Thus,
their reduction requires harsh conditions (high pressures and
6
temperatures) and continues to be a challenging goal. In
general, the hydrogenation of amides proceeds through
Scheme 1 Possible reaction pathways for the hydrogenation of
amides.
a
Leibniz-Institut f u¨ r Katalyse, e.V. Albert-Einstein Str. 29a, 18059 Rostock, Germany.
E-mail: matthias.beller@catalysis.de
b
Instituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Tr. La Crucca
3
, 07100 Sassari, Italy
†
Electronic supplementary information (ESI) available: General experimental
Scheme 2 Hydrogenation of amides to alcohols and amines catalyzed
procedures, additional schemes and gures, characterization data and NMR
by: (a) ruthenium (previous work), (b) iron (previous work) and (c)
manganese (this work). See ESI for other examples of Ru–pincer
a
spectra are available. See DOI: 10.1039/c7sc00138j
‡
V. P. and J. R. C.-A. contributed equally to this work.
catalysts reported for this reaction (Scheme S1†).
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9d
2
removal of H O (Scheme 1, path A), while the C–N cleavage the alkylated amine via a hydrogen borrowing mechanism. In
produces the deprotected amine and the corresponding alcohol addition, an elegant deoxygenative hydrogenation of amides
by collapse of the intermediate hemiaminal (Scheme 1, path B). using a well-dened iridium pincer complex in the presence of
10
In the past decade, signicant improvements in amide a stoichiometric amount of boron Lewis acid was also reported.
hydrogenation using both heterogeneous and homogeneous On the other hand, homogeneous pincer catalysts making
11
catalysts have been achieved. While some of the heterogeneous use of metal–ligand cooperation, have shown notable activity
catalysts, e.g. Re–Pd/C, work under comparably mild conditions, for the hydrogenation of the amide by C–N bond cleavage
they proceed via path A (Scheme 1). Notably, these precious metal (Scheme 1, path B). This transformation allows to obtain alco-
systems are incompatible with aromatic and some other sensitive hols and amines from amides and is of interest as selective
8
functional groups which can be easily reduced. No hydrogena- deprotection methodology in organic synthesis.
tion of aromatic rings has been observed using homogeneous
The rst example of this hydrogenolysis of amides to alco-
ruthenium/1,1,1-tris(diphenylphosphino-methyl)ethane (triphos)- hols and amines was reported by Milstein using a well-dened
12
based systems in combination with specic acidic additives, as ruthenium pincer complex. Subsequently, other examples,
reported by Cole-Hamilton's, Leitner and Klankermayer's, Qi-Lin mainly based in ruthenium, were published by Ikariya, Saito,
2b,9
13
Zhou's groups.
Recently, we have demonstrated that such Bergens, Mashima, Zhang and our group (Scheme 2(a)).
catalysts also reduce the amide carbonyl group to the hemi-
In general, the replacement of noble metals with inexpensive
aminal, which collapses to give the alcohol and the non-alkylated and abundant rst row metals is an actual goal for catalysis as well
amine (pathway B). Interestingly, these compounds then produce as organometallic chemistry and attractive in terms of
Scheme 3 Synthesis of pincer ligand (1) and manganese complexes (Mn-1, Mn-2 and Mn-3).
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amines under relatively mild conditions. In addition, more
challenging substrates like primary benzamides could be hydro-
genated in moderate yields. To the best of our knowledge, with
the exception of the previously reported iron-based systems, there
is no another example of this transformation catalyzed by non-
noble metal-based catalytic system.
Results and discussion
Ligand and metal complex synthesis
In previous studies, the important role of pincer ligands for
19
Fig. 1 Molecular structure of manganese complex Mn-2 with thermal bifunctional hydrogenations was claried. While most cata-
ellipsoids drawn at the 30% probability level. Hydrogen atoms other
than H3 have been omitted for the sake of clarity.
lysts are based on PNP ligands, other complexes which combine
so and hard donors and/or hemilabile groups have been
2a,20
12b
shown to be benecial in ester
and amide reduction.
14
sustainability. Recent efforts by Milstein's, Sanford's and Lang- Following our previous work concerning the synthesis of the
er's groups in this direction have led to the development of three NNP-type imidazolylphosphine pincer ligand family and the
21
homogeneous iron based catalysts for this important trans- corresponding ruthenium complexes, that were successfully
15
15
13g
formation (Scheme 2(b)). However, catalysts Fe-1 or Fe-2(a, b)
applied in amide hydrogenation, we envisaged the possibility
afforded modest conversions and yields, and/or required forcing to prepare the rst Mn–NNP imidazolylphosphine pincer
conditions, or have a narrow scope which is limited to activated complexes and to test their potential as reduction catalysts. For
substrates like uorine-containing amides or formamides.
this purpose, initially the NNP pincer ligand 2-(diisopropyl-
In addition to iron, manganese is one of the most abundant phosphanyl)-N-[(1-methyl-1H-imidazol-2-yl)methyl]ethan-1-
metals in the earth crust and plays an important role in human amine 1 (Scheme 3), was prepared in a one-pot two-step syn-
1
3g,21
biochemistry. In general, Mn-based complexes were employed in thesis.
catalytic oxidation reactions. Moreover, special hydrosilylation available Mn(CO) Br in toluene upon irradiation with UV light
When ligand 1 was reacted with commercially
5
16
22
and electrocatalytic reactions were reported. Very recently, the for 3 hours, Mn-1 was obtained in 60% yield (Scheme 3). To
design and development of new Mn-based complex catalysts for our delight the complex was crystallized by vapour diffusion of
other applications, e.g. reduction reactions, became very appea- n-heptane into a concentrated DCM solution of the compound
16b,17,18
ling.
In this context, here we describe the synthesis of three and the molecular structure was determined by X-ray diffraction
novel well-dened Mn–pincer complexes and their catalytic (Fig. S1,† ESI). The molecular structure shows a distorted
application in the efficient and selective hydrogenation of trigonal bipyramidal geometry in which the ligand is coordi-
secondary and tertiary amides to the corresponding alcohols and nated to the manganese in a tripodal fashion.
Table 1 Hydrogenation of benzanilide 2 to aniline 3 and benzyl alcohol 4 with manganese complexes Mn-1–3
a
ꢀ
t
b
b
b
Entry
H
2
(bar)
T ( C)
Mn-cat. (mol%)
KO Bu (mol%)
Conv. (%)
3 (%)
4 (%)
1
2
3
4
5
6
7
8
9
50
50
50
50
50
50
30
30
30
30
30
30
30
130
130
130
130
130
130
130
120
120
120
120
120
120
—
15
15
15
15
—
10
10
10
10
8
—
—
>99
—
—
>99
>99
>99
98
95
72
—
—
>99
—
—
97
96
>99
90
89
65
45
32
—
—
98
—
—
91
93
90
89
82
62
40
29
Mn-1 (4)
Mn-2 (4)
Mn-3 (4)
Mn-2 (4)
Mn-2 (4)
Mn-2 (4)
Mn-2 (4)
Mn-2 (2.5)
Mn-2 (2.5)
Mn-2 (2.5)
Mn-2 (2.5)
Mn-2 (1.5)
1
1
1
1
0
1
2
3
6
4
8
51
47
a
t
2
Standard reaction conditions: benzanilide 2 (49.30 mg, 0.25 mmol), Mn-cat. (2.5–4 mol%), KO Bu (4–15 mol%), t-amylOH (2 mL), 30–50 bar of H ,
ꢀ
b
1
20 C over 16 h. Conversion of 2 and yields of 3 and 4 were calculated by GC using hexadecane as external standard.
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Fig. 2 Study of the solvent effect in the hydrogenation of benzanilide 2 to aniline 3 and benzyl alcohol 4 catalyzed by Mn-2 complex. Standard
t
reaction conditions: benzanilide 2 (49.30 mg, 0.25 mmol), Mn-2 (1.78 mg, 0.00375 mmol, 1.5 mol%), KO Bu (2.13 mg, 0.019 mmol, 8 mol%),
ꢀ
solvent (2 mL), 30 bar of H
2
, 120 C over 16 h. Conversion of 2 and yields of 3 and 4 were calculated by GC using hexadecane as external standard.
In addition, a Mn(I) complex was prepared by addition of the
manganese precursor to ligand 1 in ethanol at 90 C in the catalysts under 50 bar of H
absence of light. In this way the tris-carbonyl ionic NNP Mn(I) excess of base and t-amyl alcohol as solvent. Under these
complex Mn-2 is formed in 95% yield (Scheme 3). Crystals conditions only complex Mn-2 showed activity affording products
suitable for X-ray diffraction analysis were obtained by slow 3 and 4 in quantitative yields (Table 1, entry 2–4). Next, variations
evaporation of an ethanolic solution under a gentle ow of
Initially the three complexes were tested using 4 mol% of Mn
ꢀ
ꢀ
2
and 130 C in the presence of a slight
24
argon. Compared to complex Mn-1 the molecular structure
Table 2 Hydrogenation of benzanilide 2 to aniline 3 and benzyl
alcohol 4 with manganese complex Mn-2: fine tuning of reaction
conditions
23
shown in Fig. 1 exhibits a distorted octahedral geometry in
which the PNN ligand adopts a facial coordination, one CO
ligand is trans to the central aliphatic nitrogen, thus acting as
a tripodal ligand rather than pincer, similar to the previously
18h
reported PNP–Mn complex. The structure of Mn-2 was further
proven by NMR and IR spectroscopy, high resolution mass
spectroscopy and elemental analysis (Fig. S9, see ESI†).
1
In general, the complex has a low molecular symmetry (C is
t
b
b
b
T
( C)
Mn-2
(mol%)
KO Bu
Conv.
(%)
3
4
the symmetry point group) and its IR spectrum shows three
bands in the carbonyl region at 2027, 1943 and 1916 (partly
a
ꢀ
Entry
(mol%)
(%)
(%)
À1
overlapping) cm which demonstrates the presence of three
1
2
3
4
120
100
100
100
100
100
80
100
100
100
1.5
2
2
2
2
1.5
2
2
2
2
8
10
8
>99
>99
95
29
58
79
18
—
96
96
88
24
57
67
8
—
—
53
90
90
80
24
44
60
—
—
—
50
CO molecules coordinated to the metal center.
For comparative catalytic studies, in addition to the two well-
dened Mn-1 and Mn-2 NNP pincer complexes, the synthesis of
an ionic PNP Mn(I) complex Mn-3 was also performed (the
molecular structure of this complex is shown in Fig. S10, see
ESI†). All the complexes synthesized are stable and do not
decompose easily in the presence of air, the catalytic properties
result unaltered aer one month.
5
c
5
10
10
10
10
10
10
6
7
d
8
e
9
—
63
f
10
a
Standard reaction conditions: benzanilide 2 (49.30 mg, 0.25 mmol),
t
Mn-2 (1.5–2 mol%), KO Bu (5–10 mol%), cyclohexane (2 mL), 15–30
Catalytic hydrogenation of amides using Mn–pincer
complexes
ꢀ
2
, 100–120 C over 16 h. Conversion of 2 and yields of 3 and
c
b
bar of H
were calculated by GC using hexadecane as external standard. Run
4
d
at 15 bar of H
2
.
Run with 2 mol% of ligand 1 in the absence of Mn-2
complex. f Run with 2 mol% of Mn(CO) Br in the absence of Mn-2
complex. Run with 2 mol% of ligand 1 and 2 mol% of Mn(CO) Br.
To test the potential of the new complexes as catalysts, the
hydrogenation of benzanilide 2 to afford aniline 3 and benzyl
alcohol 4 was chosen as benchmark reaction.
e
5
5
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Table 3 Substrate scope in the hydrogenation of amides to alcohols and amines catalyzed by Mn-2 complex
a
b
b
b
Entry
Amide
Mn-2 (mol%)
Conv. (%)
Yield of amine (%)
Yield of alcohol (%)
1
2
>99
94
96
88
90
85
2
3
2
2
>99
90
n.d.
4
5
6
7
2
4
4
3
90
84
80
85
81
75
>99
94
>99
85
>99
80
c
8
3
4
>99
95
>99
94
90
90
9
1
1
0
1
4
4
85
82
98
80
94
>99
1
1
2
4
4
95
92
90
c
3
>99
>99
>99
d
1
1
4
2
2
95
82
90
81
85
78
c,d
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Table 3 (Contd.)
a
b
b
b
Entry
Amide
Mn-2 (mol%)
Conv. (%)
Yield of amine (%)
Yield of alcohol (%)
d
1
6
3
>99
>99
>99
>99
>99
90
c,d
1
7
4
5
c,d
1
8
98
97
96
a
t
Standard reaction conditions: amide (0.25 mmol), Mn-2 cat. (2–5 mol%), KO Bu (2.8 mg, 0.025 mmol, 10 mol%), cyclohexane (2 mL), 30 bar of H
2
,
ꢀ
00 C over 16 h. Conversion of the amide and yield of the alcohol and amine were calculated by GC using hexadecane as external standard. The
d
b
c
1
ꢀ
reaction was carried out using cyclohexane/t-amylOH (1.5/0.5) mixture as solvent (2 mL). Run at 120 C.
of pressure, temperature, catalyst loading and base concentration
In contrast, a substantial decrease of base loadings had
were performed (Table 1, entry 6–13). It was found that Mn-2 was a signicant impact (Table 2, entries 3 and 4). Additional
ꢀ
efficient also under milder conditions (30 bar of H
2
, 120 C, 10 mitigation of the reaction temperature, hydrogen pressure and
t
mol% KO Bu), even if the catalyst loading was reduced to 2.5 mol% catalyst loading had negative effects on the activity (Table 2,
Table 1, entry 9) and the products 3 and 4 were obtained in 90% entries 5–7). Finally, when the reaction was conducted in the
(
and 89% yields, respectively. However a further reduction of the presence of either ligand 1 or metal precursor no conversion
amount of catalyst or base was detrimental (Table 1, entries 10–13). was observed (Table 2, entries 8 and 9). Noticeable, in situ
Notably, no reaction took place in the absence of base as predict- combination of Mn(CO)
5
Br and ligand 1 also afforded moder-
able in a system with non-innocent pincer ligand (Table 1, entry 5). ated activity in the reaction (Table 2, entry 10).
This effect of the base suggests that the active catalytic species is
At this stage we decided to study the general applicability of
the amido complex, obtained by deprotonation of N–H and the novel Mn-2 complex in the hydrogenation of a wide range of
resulting in the release of one CO molecule. Then the proposed different secondary and tertiary amides to the corresponding
mechanism mights be the outersphere catalytic cycle already alcohols and amines (Table 3). Most substrates were hydroge-
investigate in previous work regarding hydrogenation of carboxylic nated in good to excellent yields under the previously selected
2a,13g,18g,h
ꢀ
derivatives catalyzed by these type of pincer complexes.
optimized conditions at 100 C, 30 bar of hydrogen over 16 h
Next, we explored the solvent effect on the catalytic activity of using cyclohexane as solvent.
Mn-2 (Fig. 2).
In order to observe positive or negative effects of the different
solvents, the screening was carried out at 30 bar of H
2
and
ꢀ
120 C using 1.5 mol% Mn-2 and 8 mol% of base. Surprisingly,
among all the solvents tested (more than 13), cyclohexane was
found to give the best results for this system (Fig. 2). This is
a rather unexpected effect for this type of reactions and ether-,
alcohol-, arene-, and uorinated-solvents as well as other
alkanes provided signicantly lower activities. In this context, it
is interesting to note that cyclohexane allowed for efficient
transfer hydrogenation of nitriles catalyzed by a well-dened
Scheme 4 Hydrogenation of primary amides to corresponding alco-
hols catalyzed by Mn-2 complex. Standard reaction conditions: amide
25
t
NNP Co imidazolylphosphine pincer complex.
(0.25 mmol), KO Bu (3 eq. to Mn), cyclohexane/t-amylOH (1.5/0.5)
ꢀ
mixture (2 mL), 50 bar of H
2
and 140 C. Specific reaction conditions
Having identied cyclohexane as the best solvent for our
reaction, a ne tuning of the initially selected optimized
conditions was carried out. Catalytic activity did not decrease
for benzamide: Mn-2 (5 mol%) over 48 h, for nicotinamide: Mn-2 (7
mol%) over 24 h, for p-(trifluoromethyl)benzamide and 4-methox-
ybenzamide: Mn-2 (5 mol%), over 24 h. Conversion of the amide and
yields of the corresponding benzyl alcohols were calculated by GC
using hexadecane as external standard.
ꢀ
ꢀ
when the temperature was reduced from 120 C to 100 C and
the catalyst loadings from 2.5 to 2 mol% (Table 2, entry 2).
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Even less reactive electrophilic amides were converted in very SmI
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12c
2
-based system
and the well-dened NNP ruthenium
ꢀ
good yields using up to 5 mol% catalyst loading at 100–120 C. For imidazolylphosphine pincer complex previously reported by
13g
instance, reduction of different uoro- and chloro-substituted us. Therefore, at this stage we explored the hydrogenation of
amides proceeded smoothly and no dehalogenation products different benzamides in the presence of Mn-2 (Scheme 4). To
were detected. Notably, also highly sensitive iodide was fully our delight, benzamide and p-methoxybenzamide but also
tolerated (Table 3, entries 4–8 and 13). Gratifyingly, benzyl- a heterocyclic primary amide such as nicotinamide and acti-
substituted amides (Table 3, entry 11) and amides containing vated 4-(triuoromethyl)benzamide afforded moderate to good
electron-donating groups such as methoxy afforded very high conversion (50–65%) with high selectivity.
conversions (Table 3, entries 12 and 15). Noticeably, Mn-2 allowed
Apart from aromatic and aliphatic amides also the parent
the hydrogenation of N-acetyl-1,2,3,4-tetrahydroquinoline (Table formamides including alkylformamides such as N-octylforma-
3, entry 2), as well as N-(naphthalen-1-yl)acetamide (Table 3, entry mide (Table 4, entry 4) or N-cyclohexylformamide (Table 4, entry
14) and important bioactive pyridine-containing amides (Table 3, 5) are smoothly hydrogenated under the previously optimized
entries 17 and 18).
conditions. Even using lower catalyst loadings (1 mol% of Mn),
Tertiary amides including sterically hindered substrates full conversion was obtained (Table 4, entry 2). To show the
were also successfully hydrogenated in the presence of this applicability of our PNN pincer complex Mn-2 nally hydroge-
manganese complex. Thus, N,N-diphenylacetamide (Table 3, nation of the herbicide diufenican was investigated (Scheme 5).
entry 10) and triuoromethyl-activated amides (Table 3, entries For the rst time, this herbicide could be catalytically hydroge-
3
and 16) afforded excellent conversion and yields.
nated to the corresponding alcohol and amine under relatively
Unfortunately the reduction of aliphatic N-alkyl amide as mild conditions affording good conversion.
N,N-dimethyloctanamide or non activated N-alkyl substituted
In order to check the selectivity of the Mn-2 pincer complex,
benzamides, failed with this catalytic system.
hydrogenations of benchmark amides in the presence of
So far, hydrogenation of primary amides – more challenging additional reducible groups like carbamate or urea were
substrates – to the corresponding alcohols and ammonia has carried out (Scheme 6). To our delight, using catalyst Mn-2
12b
been scarcely investigated.
Few examples of reduction highly selective reduction of benzanilide 2 and N-acetyl-
systems are known to be active for this type of substrates such as 1,2,3,4-tetrahydroquinoline to the corresponding alcohols
Table 4 Hydrogenation of different formamides to the corresponding amines and methanol catalyzed by Mn-2 complex
a
b
b
b
Entry
Formamide
Conv. (%)
Yield of amine (%)
Yield of alcohol (%)
1
2
>99
>99
95
92
90
88
c
3
4
90
83
85
83
80
80
5
>99
>99
>99
>99
>99
>99
d
6
e
7
>99
>99
>99
a
t
Standard reaction conditions: formamide (0.25 mmol), Mn-2 cat. (2.37 mg, 0.005 mmol, 2 mol%), KO Bu (2.8 mg, 0.025 mmol, 10 mol%),
ꢀ
2
, 100 C over 16 h. Conversion of the formamide and yield of the amine and methanol were calculated by GC
c d
b
cyclohexane (2 mL), 30 bar of H
using hexadecane as external standard. The reaction was carried out with 1 mol% of catalyst. The reaction was carried out with 3 mol% of
catalyst. The reaction was carried out at 120 C.
e
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catalyses efficiently the selective hydrogenation of a wide range of
amides to the corresponding alcohols and amines under relatively
mild conditions. Activated and non-activated secondary and
tertiary amides and the more challenging primary amides can be
hydrogenated to the corresponding products in high yields. To
highlight the versatility of the protocol, the reduction of a more
complex amide such as diufenican is also included. To the best
of our knowledge, this is the rst example of Mn-catalyzed
hydrogenation of amides. Different hydrogenation experiments
have shown the excellent selectivity of the new manganese pincer
complex for the hydrogenation of amides in the presence of other
Scheme 5 Selective hydrogenation of diflufenican to the corre-
sponding alcohol and amine catalyzed by Mn-2 complex. Reaction
conditions: diflufenican (98.6 mg, 0.25 mmol), Mn-2 cat. (5.92 mg,
t
0
.0125 mmol, 5 mol%), KO Bu (2.8 mg, 0.025 mmol, 10 mol%), reducible groups. This fact opens the door to the potential
cyclohexane (2 mL), 30 bar of H , 130 C over 16 h. Conversion of application of this type of earth-abundant metal pincer complexes
ꢀ
a
2
amide and yield of amine was calculated by GC using hexadecane as
in organic synthetic deprotection methodologies.
b
1
external standard. The yield was calculated by H NMR using 1,3,5-
trimethoxybenzene as external standard.
Experimental details
General procedure for the hydrogenation of amides
A 4 mL glass vial containing a stirring bar was sequentially
charged under argon with amide (0.25 mmol) and complex Mn-
2
(1–7 mol%). Aerwards, the reaction vial was capped with
a septum equipped with a syringe needle and set in the alloy
plate and the vial was purged with 3 cycles of vacuum and
argon. Cyclohexane or cyclohexane/t-amyl alcohol (1.5/0.5)
mixture (2 mL) and the corresponding catalytic amount of
t
KO Bu were sequentially added under argon and the vial was
then placed into a 300 mL autoclave. Once sealed, the autoclave
was purged three times with 20 bar of hydrogen, then pressur-
ized to the desired hydrogen pressure (30–50 bar), and placed
into an aluminum block that was preheated to the desired
ꢀ
temperature (80–140 C). Aer the desired reaction time of
1
6–48 h, the autoclave was cooled in an ice bath and the
remaining gas was carefully released. Finally, n-hexadecane
20 mg) was added as an external standard, and the reaction
(
mixture was diluted with ethyl acetate and analyzed by gas
chromatography.
Scheme 6 Mn-catalyzed selective hydrogenations of benzanilide 2
and N-acetyl-1,2,3,4-tetrahydroquinoline in the presence of tert-
butyl-N-methylcarbamate (a) and (c) or diphenyl urea (b) and (d).
Standard reaction conditions: substrate (0.25 mmol each one), Mn-2
Acknowledgements
We thank the state of Mecklenburg-Vorpommern and the BMBF
for nancial support. We would like also to thank the excellent
t
cat. (2.37 mg, 0.005 mmol, 2 mol%), KO Bu (2.8 mg, 0.025 mmol, 10
ꢀ
mol%), cyclohexane (2 mL), 30 bar of H
2
, 100 C over 16 h. Conversion technical and analytical staff of the LIKAT for their support. The
of the starting material and yield of the products were calculated by
GC using hexadecane as external standard.
authors would like to dedicate this work to Professor Francesco
Ruffo, “Universit ´a degli Studi di Napoli Federico II” and thank
Dr Rosa Adam Ort ´ı z for the intense exchange of ideas regarding
this project.
and amines can be performed in the presence of both tert-
butyl-N-methylcarbamate (Scheme 6, eqn (a) and (c)) or N,N-
diphenylurea (Scheme 6, eqn (b) or (d)). It is noteworthy, that
these results pave the way towards selective deprotection
strategies in organic synthesis mediated by this NNP pincer
complex.
Notes and references
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Conclusions
Different well-dened manganese–PNN pincer complexes have
been synthetized for the rst time. One of these complexes Mn-2
Chem. Sci.
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