Glycerol Boosted Rh-Catalyzed Hydroaminomethylation Reaction: A Mechanistic Insight

Article abstract of DOI:10.1002/chem.202001978

We report a Rh-catalyzed hydroaminomethylation reaction of terminal alkenes in glycerol that proceeds efficiently under mild conditions to produce the corresponding amines in relatively high selectivity towards linear amines, moderate to excellent yields by using a low catalyst loading (1 mol % [Rh], 2 mol % phosphine) and relative low pressure (H₂/CO, 1:1, total pressure 10 bar). This work sheds light on the importance of glycerol in enabling enamine reduction via hydrogen transfer. Moreover, evidence for the crucial role of Rh as chemoselective catalyst in the condensation step has been obtained for the first time in the frame of the hydroaminomethylation reaction by precluding deleterious aldol condensation reactions. The hydroaminomethylation proceeds under a molecular regime; the outcome of catalytically active species into metal-based nanoparticles renders the catalytic system inactive.

Full text of DOI:10.1002/chem.202001978

Accepted Article
Accepted Article
Title: Glycerol boosted Rh-catalyzed hydroaminomethylation reaction,
a mechanistic insight
Authors: Alejandro Serrano-Maldonado, Trung Dang-Bao, Isabelle
Favier, Itzel Guerrero-Ríos, Daniel Pla, and Montserrat
Gómez
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
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published online in Early View as soon as possible and may be different
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content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.202001978
Link to VoR: https://doi.org/10.1002/chem.202001978
01/2020

10.1002/chem.202001978
Chemistry - A European Journal
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Glycerol boosted Rh-catalyzed hydroaminomethylation reaction,
a mechanistic insight
Alejandro Serrano-Maldonado,[a] Trung Dang-Bao,§[b] Isabelle Favier,[b] Itzel Guerrero-Ríos,*[a] Daniel
Pla,*[b] and Montserrat Gómez*[b]
Dedicated to the memory of Prof. Erika Martin (1963–2017)
[a]
[b]
§
A. Serrano-Maldonado, Prof. I. Guerrero-Ríos
Departamento de Química Inorgánica, Facultad de Química
Universidad Nacional Autónoma de México
Av. Universidad 3000, 04510 CDMX, Mexico
E-mail: itzelgr@unam.mx
T. Dang-Bao, Dr. I. Favier, Dr. D. Pla, Prof. M. Gómez
Laboratoire Hétérochimie Fondamentale et Appliquée
Université Toulouse 3 – Paul Sabatier, CNRS UMR 5069
118 route de Narbonne, 31062 Toulouse Cedex 9, France
E-mail: pla@lhfa.fr, gomez@chimie.ups-tlse.fr
Current address: Faculty of Chemical Engineering
Ho Chi Minh City University of Technology, VNU-HCM
268 Ly Thuong Kiet, District 10, Ho Chi Minh City, Vietnam
Supporting information for this article is given via a link at the end of the document and contains a general experimental section, optimization data, control
tests, reaction monitoring and characterization data of selected organic compounds (1H and 13C NMR, MS).
Abstract: In this contribution, we report
a
Rh-catalyzed
giving water as the only concomitant product.[2a-g, 3] HAM is very
attractive from an atom economy viewpoint, however it often
requires harsh conditions, in particular using Rh-based
systems,[2a-g] despite its well-known ability to catalyze
hydroformylation processes.[4] In order to overcome this drawback,
it is essential to design catalytic systems able to promote both
hydroformylation and hydrogenation steps under relative mild
conditions. In the literature, this approach has been considered
and systems involving two catalysts have been described.
Actually, Xiao[5] and Han[6] have employed a Rh-based catalyst
together with an optically pure phosphoric acid as organocatalyst
promoting imine hydrogenation towards the synthesis of chiral
secondary amines, from styrene and aniline derivatives under
mild conditions (total pressure: 2 – 11 bar; 25 – 50 °C; 16 – 72 h).
For the synthesis of linear amines, Beller and coworkers reported
a catalytic system constituted by Rh(I) and Ir(I) precursors (Ir/Rh
ratio ca. 10/1) in the presence of an excess of TPPTS, taking
advantage of the known performance of Ir-based systems in the
hydrogenation of imines and enamines,[7] leading to primary
amines from terminal alkenes and ammonia (total pressure 78
bar; 110 – 130 °C; 5 – 10 h) with high regioselectivity (linear
amines) and good chemoselectivity (primary amines) (Scheme
1a).[8] More recently, Hartwig’s group has also reported a Rh/Ir
catalytic system constituted by [Rh(acac)(CO)2]/BISBI (BISBI =
2,2'-bis(diphenylphosphinomethylene)-1,1'-biphenyl) and Xiao’s
catalyst, an Ir(III) organometallic complex stable in the presence
of carbon monoxide;[9] this catalytic system permits to work under
milder conditions (total pressure 3.4 bar; 80 °C; 20 h), producing
secondary linear amines from good to high yields, using a mixture
of solvents (toluene/methanol) and an aqueous buffer solution of
NaHCO2 (Scheme 1b). Notably, the role of bidentate ligands,
such as the diphosphine BISBI, has proven to be key for such
high regioselectivities.[10]
hydroaminomethylation reaction of terminal alkenes in glycerol
that proceeds efficiently under mild conditions to produce the
corresponding amines in relatively high selectivity towards linear
amines, moderate to excellent yields using a low catalyst loading
(1 mol% [Rh], 2 mol% phosphine) and relative low pressure
(H2/CO, 1:1, total pressure 10 bar). This work sheds light on the
importance of glycerol in enabling enamine reduction via
hydrogen transfer. Moreover, the crucial role of Rh as
chemoselective catalyst in the condensation step has been
evidenced for the first time in the frame of the
hydroaminomethylation reaction by precluding deleterious aldol
condensation reactions. The hydroaminomethylation proceeds
under a molecular regime; the outcome of catalytically active
species into metal-based nanoparticles renders the catalytic
system inactive.
Introduction
Among nitrogen compounds, amines play an important role as
feedstock chemicals with a production on million-ton scale
annually in the synthesis of agrochemicals, pharmaceuticals,
solvents, dyes, monomers for polymerizations and functional
materials, among the most important applications.[1] Despite the
production of amines often requires expensive and sometimes
toxic
substances
through
conventional
methods,
hydroaminomethylation (HAM) of alkenes offers an alternative
synthesis from an environmental and economic point of view.[2]
HAM is a multi-component tandem transformation that consists of
three consecutive steps: the metal-catalyzed hydroformylation of
an alkene, followed by condensation of the resulting aldehyde
with an amine leading to an enamine (or imine/iminium)
intermediate that undergoes metal-catalyzed hydrogenation,
1
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Based on these precedents and taking into account the properties
of glycerol as solvent in a wide range of transformations,[11] mainly
involving metal-catalyzed homogeneous processes,[12] but also
metal nanoparticles[13],[14] and catalyst-free reactions,[15] we
envisaged to explore the role of glycerol as hydrogen donor in the
HAM
reaction
of
terminal
olefins
catalyzed
by
[Rh(acac)(CO)2]/TPPTS system through enhancing the reductive
amination, which often is the rate limiting step of the HAM reaction
(Scheme 1c).[16] This contribution aims to provide a mechanistic
insight, in particular related to the role of rhodium in the
amine/aldehyde condensation step and the hydrogenation of the
resulting enamine, in glycerol under mild reaction conditions.
Scheme 2. Hydroaminomethylation benchmark reaction of Rh-catalyzed oct-1-
ene (1) and morpholine (a). By-products from 1 are also indicated (1H and 1l).
When toluene or dioxane were used, full conversion was
observed (entries 2 and 3, Table 1), showing moderate
chemoselectivity towards the HAM product due to competing
olefin isomerization (mixture of internal alkenes) and substrate
hydrogenation, albeit regioselectivity was similar for both solvents,
leading to ca. 3:2 linear to branched ratio of 1a. Despite the high
conversion and high chemoselectivity towards the formation of
amines obtained in cyclopentyl methyl ether (CPME), the reaction
was not regioselective (entry 4, Table 1). Given the reported
efficiency of alcohols in promoting HAM reactions,[17] we sought
to evaluate the effect of other protic solvents than glycerol.
Whereas the use of water (entry 5, Table 1) led to an inactive
catalytic system, both MeOH and butan-1-ol presented higher
olefin isomerization (entries 6 and 7, Table 1) than glycerol (entry
1, Table 1). Thus, glycerol provided the best results in terms of
chemo- and regioselectivity towards the formation of 1a,
outperforming both non-protic and other protic solvents in terms
of deleterious olefin isomerization/hydrogenation side-reactions.
Scheme 1. Strategies to conduct the multi-step HAM reaction under tailored
conditions for the synthesis of primary amines.
Results and Discussion
Based on the established HAM mechanism, terminal alkenes are
initially transformed into the corresponding linear and branched
aldehydes by hydroformylation, which then react with an amine to
produce the corresponding enamine by a condensation reaction.
Hydrogenation of these latter intermediates affords the expected
amines, provided that side-reactions such as alkene
isomerization or hydrogenation are precluded (Scheme 2,
illustrating the case of oct-1-ene and morpholine).
We chose the HAM reaction of oct-1-ene (1) and morpholine (a)
catalyzed by [Rh(acac)(CO)2]/TPPTS in glycerol as benchmark
reaction (Scheme 2). Under optimized conditions, high
chemoselectivity was obtained towards the formation of amines
1a at 120 °C and 10 bar (total pressure) of an equimolar CO:H2
mixture, only observing minor alkene isomerization (less than
10%; see entry 1 in Table 1). Notably, the use of the diphosphine
BISBI instead of TPPTS exhibited lower reactivity (50%
conversion) and no selectivity enhancement (l-1a / b-1a, 70/30).
The reaction optimization survey in terms of temperature,
pressure, time, Rh/phosphine ratio and solvent (for further details,
see Tables S1 and S2 in the Supporting Information) raised
concerns on crucial solvent effects that merit a special discussion.
Table 1. Rh-catalyzed HAM of oct-1-ene and morpholine in different solvents.[a]
Selectivity[b]
Conv.
Entry Solvent
(%)[b]
1I (%) 1H (%) 1a’’(%) 1a (%)
l-1a/b-1a
80/20
65/35
66/34
50/50
nd
1
2
3
4
5
6
7
Glycerol
Toluene
Dioxane
CPME
95
98
7
nd
23
14
nd
nd
nd
nd
nd
nd
nd
nd
nd
nd
nd
93
56
60
95
nd
81
73
21
26
nd
nd
19
26
99
>99
<5
H2O
MeOH
99
70/30
70/30
Butan-1-ol
>99
[a] General conditions: 1 mmol of 1-octene, 1.5 mmol of morpholine, 1 mol%
[Rh(acac)(CO)2], 2 mol% TPPTS, 2 mL of solvent, 5 bar CO / 5 bar H2 (pressure
at room temperature), 120 °C, 6 h; nd = not determined; see Scheme 2 for the
labelling of compounds. [b] Conversion, selectivity and linear/branched ratio
were determined by GC employing n-dodecane as internal standard. [c] Carried
out at 80 °C. [d] 8% of aldehyde 1a’ detected by GC-MS.
2
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Taking into account the remarkable effect of glycerol and given
the fact that hydrogenation of the imine-, iminium- or enamine-
type intermediates is generally accepted as the rate determining
step for Rh-catalyzed HAM,[2a, 18] we considered that a hydrogen
transfer (glycerol as reducing agent) could be operative in addition
to the hydrogenation reaction,[11e] enabling low pressure
conditions while overriding the need for a metal-based co-
catalyst.[9] Thus, the nature of the hydrogen donor was further
assessed with glycerol and butan-1-ol at 80 ºC, revealing that
enamine reduction was faster in the latter albeit with moderate 1a
selectivity (entries 1 and 2, Table 2). The effect of glycerol in
boosting enamine reduction was observed when a solvent
mixture of glycerol and butan-1-ol (0.25:0.75) was used, yielding
a quantitative conversion and full chemoselectivity towards 1a,
showing a slight decrease in terms of regioselectivity (entries 1
and 2 vs 3, Table 2).
We next investigated whether the in-situ generated aldehydes in
the initial hydroformylation step of the HAM process could also
undergo hydrogen transfer processes under the optimized
reaction conditions. Thus, a control test with nonanal (l-1’) was
carried out but no formation of nonan-1-ol was observed;
alternatively, acetals from the reaction of the aldehyde and
glycerol were obtained, because acetalization is probably faster
than hydrogen transfer reaction.[21]
We then focused on the reactivity of aldehydes towards enamine
formation and subsequent reduction to give the desired amine
products, while avoiding aldol condensation pathways (Table 3).
Accordingly, the following control tests were carried out. First, the
condensation between nonanal (l-1’) and morpholine (a) using a
1/1.5 molar ratio of reagents under inert atmosphere at 120 °C in
the presence of catalyst, afforded full conversion but mainly
yielding the aldol condensation product (62%) together with only
38% of the desired l-1a product (coming from the reduction of
enamine l-1a’’ by glycerol as discussed above; entry 1, Table 3).
Under H2/CO pressure, the formation of l-1a was slightly improved
(entry 2, Table 3). However, in the absence of catalyst, the aldol
product was favored (up to 88%; entry 3, Table 3), indicating the
benefic role of the Rh/TPPTS system in terms of chemoselectivity.
The selectivity towards the desired amine substantially enhanced
when a large excess of morpholine was used (l-1’/a ratio of 0.1/3),
leading up to 71% of l-1a (entry 4, Table 3). These latter
conditions, but under H2/CO pressure, gave 98% of l-1a (entry 5,
Table 3); in the absence of catalyst, aldol condensation products
were obtained up to 49% yield (entry 6, Table 3), in agreement
with the trend observed using a lower excess of morpholine (entry
3, Table 3). These results proved that both a low concentration of
aldehyde (probably shifting the equilibrium towards the formation
of enamine l-1a’’ by the amine excess) and the presence of the
rhodium catalyst are necessary in order to prevent the formation
of aldol condensation products, as well as the reducing effect of
glycerol facilitating the enamine reduction. Consequently, under
catalytic conditions, the condensation step must be fast enough
to avoid the accumulation of aldehydes throughout reaction;
rhodium seems to play a non-innocent role in the chemoselectivity,
hampering the formation of aldol condensation products (entries
5 vs 6, Table 3). This reactivity behavior was corroborated by the
GC-MS monitoring of the benchmark reaction under catalytic
conditions (see below).
Table 2. Rh-catalyzed enamine reduction studies of oct-1-ene and morpholine
benchmark reaction in glycerol, butan-1-ol and a mixture of both.[a]
Selectivity[b]
Solvent
(glycerol:butan-1-ol)
Conv.
(%)b
Entry
1a’’(%)
1a (%)
l-1a/b-1a
1
2
3
1:0
0:1
76
42
41
nd
50c
51d
>99
84/16
84/16
70/30
>99
>99
0.25:0.75
[a] General conditions: 1 mmol of 1-octene, 1.5 mmol of morpholine, 1 mol% of
[Rh(acac)(CO)2], 2 mol% of TPPTS, 2 mL of solvent, CO (5 bar)/H2 (5 bar),
80 °C, 6 h; see Scheme 2 for the labelling of compounds. [b] Conversion,
selectivity and linear/branched ratios were determined by GC employing n-
dodecane as internal standard; nd, not determined. [c] 8% of aldehyde 1a’
detected by GC-MS. [d] 7% of aldehyde 1a’ detected by GC-MS.
With the aim of evidencing the plausible role of glycerol as
reducing agent, the reaction of 4-[(E)-non-1-en-1-yl]morpholine
intermediate (l-1a’’)[19] in glycerol under inert atmosphere, i.e. in
the absence of molecular H2, was carried out (Scheme 3a).
Interestingly, up to 67% conversion of l-1a’’ to l-1a was obtained.
This reactivity was confirmed by the hydrogen transfer of a tertiary
enamine such as 4-(1-cyclohexen-1-yl)morpholine, yielding full
conversion towards 4-cyclohexylmorpholine (Scheme 3b).
Despite the ability of glycerol to reduce enamines,[20] l-1a’’ was
only slightly reduced in the absence of catalyst (less than 5%),
proving that enamine hydrogen transfer is catalyzed by rhodium.
Table 3. Reductive amination controls in glycerol.[a]
Selectivity[b]
l-1'/a
(mmol)
CO/H2
(bar)
Entry
Catalyst
aldol by-
product (%)
l-1a (%)
1
2
3
4
1.0/1.5
1.0/1.5
1.0/1.5
0.1/3.0
Yes
Yes
Non
Yes
0/0
5/5
5/5
0/0
38
49
62
51
Scheme 3. Rh-catalyzed hydrogen transfer reaction of 4-[(E)-non-1-en-1-
yl]morpholine (a) and 4-(1-cyclohexen-1-yl)morpholine (b) in glycerol (for 1H
NMR crude analysis, see Figure S1 in the Supporting Information).
7[c]
88
71[d]
n.d.
3
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5
0.1/3.0
0.1/3.0
Yes
Non
5/5
5/5
98
51
2
6
49[d]
[a] General conditions: nonanal (l-1'), morpholine (a),
1
mol% of
[Rh(acac)(CO)2] and 2 mol% of TPPTS unless otherwise noted, 2 mL of
glycerol, CO (5 bar) : H2 (5 bar) unless otherwise noted, 120 °C, 6 h; see Table
S3 in the Supporting Information for full details. [b] Conversion (full conversion
observed for the experiments indicated in the table), chemo- and regio-
selectivity were determined by 1H NMR and GC using n-dodecane as internal
standard; n.d., not determined. [c] 5% of the enamine l-1a” was observed. [d]
71% conversion. [d] The aldol condensation product (35%) further condenses
with morpholine to yield a by-product in 14% (m/z 335).
Despite
high
pressures
are
usually
required
for
hydroaminomethylation,[4b, 4c] the methodology described herein
permitted to work under relative low pressure. Notably, in the
absence of morpholine, the hydroformylation of oct-1-ene towards
l-1’ and b-1’ in glycerol only worked under high pressure (25 bar
H2 / 25 bar CO), favoring the formation of the branched
regioisomer (l-1’/b-1’ ratio of 36/64, see Table S4 in the
Supporting Information). Thus, this behavior suggests that the
amine is involved in the hydroformylation step,[4b, 22] probably by
coordination to the rhodium center, modifying the energy of
intermediates and transition states[23] and in consequence
influencing the rate and selectivity of the hydroformylation
reaction.[24]
In order to assess the organic compounds present throughout the
HAM reaction, reaction monitoring studies were performed by
GC-MS and FTIR (Figure 1 and Figure S3 in the Supporting
Information, respectively). The GC-MS study evidenced that the
aldehyde intermediates (l-1’ and b-1’) arising from olefin
hydroformylation, were present at rather low concentrations
throughout the reaction in agreement with the behavior observed
for the condensation step (see above). Thus, after 30 min of
reaction, the molar fraction of enamine intermediates 1a’’ is
consistently higher than the corresponding aldehyde precursors
1’, indicating that the reduction of the former represents the rate-
determining step for the overall HAM reaction. Despite the fact
that operando FTIR method did not permit the detection of
organometallic intermediates or aldehydes under catalytic
conditions due to their low concentration (see Figure S3 in the
Supporting Information), the reaction profiles of oct-1-ene (1)
conversion (disappearance of the C=C stretching band at 1641
cm-1), together with the presence of a transient enamine
intermediate 1a’’ (967 cm-1 band formation and decay) and the
formation of the amine 1a (C–N stretching band at 1031 cm-1
increase) are consistent with GC monitoring data (Figure 1) and
1H NMR analysis of the reaction mixture after the 24 h operando
FTIR monitoring (see Figure S4 in the Supporting Information; for
a control FTIR monitoring, see Figure S5).
Figure 1. Monitoring by GC-MS of the hydroaminomethylation of oct-1-ene (1)
and morpholine (a) catalyzed by Rh(I)/TPPTS catalyst in glycerol. Reaction
conditions: 1 mmol of 1, 1.5 mmol of a, 1 mol% of [Rh(acac)(CO)2], 2 mol% of
TPPTS, 2 mL of glycerol, CO (5 bar)/H2 (5 bar), 120 °C. Molar fraction of
products (xi) was determined by GC using n-dodecane as internal standard. For
detailed data, see Table S5 in the Supporting Information.
Alternative mechanisms for HAM consisting on the direct C–C
coupling of oct-1-ene with 4,4'-methylenedimorpholine aminal, N-
formylmorpholine or N-(methylene)morpholinium chloride did not
work under the optimized reaction conditions. Despite the fact Rh
nanoparticles were detected after the reaction by TEM (see
Figure S6 in the Supporting Information), preformed Rh
nanoparticles were totally inactive in the HAM benchmark
reaction (see Figure S7 in the Supporting Information), indicating
that hydroaminomethylation operates under a molecular regime.
Table 4. Reaction scope of Rh-catalyzed HAM in glycerol.[a]
Selectivity[b]
Conv.
Entry
Alkene
Amine
(%)[b]
1x (%)[c]
l-1x/b-1x
1
94
86 (14)
70/30
1
1
2
78
>99 (n.d.)
80/20[f]
3
4
5
78
77
75
84 (16)
92 (8)
75/25
70/30
1
1
1
78 (8)[d]
60/40[g]
4
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Conclusion
6
80
81
71 (10)[e]
92 (n.d.)
85/15[g]
85/15
1
This contribution sheds light on the mechanism of multi-step Rh-
catalyzed hydroaminomethylation in glycerol. For the benchmark
reaction (oct-1-ene and morpholine as reagents), we evidenced
paramount solvent effects in the reactivity of Rh-based catalytic
systems, revealing the role of glycerol as reducing agent. Actually,
we demonstrated that both Rh-catalyzed hydrogenation and
hydrogen transfer processes cooperate to favor enamine
reduction under relative low pressure (5 bar H2 / 5 bar CO).
Moreover, we have shown that the enamine formation proceeds
via a chemoselective condensation promoted by rhodium; under
these conditions aldol reactions are precluded in contrast to the
non-catalyzed organic condensation. The results described
herein highlight both the fast rhodium-promoted condensation of
the aldehyde with the amine to selectively form the enamine
intermediate, as well as the role of glycerol as a hydrogen transfer
agent, boosting the Rh-catalyzed reduction of this transient
enamines and thus permitting to work at relative low pressure.
The reaction scope of terminal alkenes and amines showed the
versatility of the process exhibiting excellent chemoselectivity
towards the formation of secondary and tertiary amines, with high
linear-to-branched regioselectivity, including styrene derivatives
(up to 85:15).
7
2
8
91
96 (n.d.)[h]
97 (n.d.)[i][j]
80/20
80/20
3
9
>99
4
[a] General conditions: 1 mmol of alkene (1 – 4), 1.5 mmol of amine (a – g), 1
mol% of [Rh(acac)(CO)2], 2 mol% of TPPTS, 2 mL of glycerol, 5 bar CO / 5 bar
H2 (pressure at room temperature), 120 °C, 6 h. [b] Conversion, chemo- and
regio-selectivity were determined by GC using n-dodecane as internal standard.
[c] In brackets, percentage of internal alkenes from oct-1-ene. [d] 14% of tertiary
amine was formed. [e] 19% of tertiary amine was formed. [f] Linear/branched
ratio determined by 1H and 13C NMR. [g] Linear/branched for the tertiary amine
was not determined. [h] 4% 4-chloroethylbenzene. [i] 3% 4-ethylanisole. [j]
Reaction conditions: 1 mmol of 4-vinylanisole, 1.5 mmol of morpholine, 1 mol%
[Rh(acac)(CO)2], 1 mol% of TPPTS in 2 mL of glycerol, 5 bar CO / 15 bar H2
(pressure at room temperature), 120 ºC, 10 h.
With the optimized experimental conditions for the benchmark
reaction, the HAM reaction scope was evaluated using primary
and secondary amines, including aniline derivatives (a – g), as
well as different terminal alkenes (1 – 4) giving high conversions
towards the expected products (75 – 94% conversion, Table 4).
Concerning chemoselectivity, for secondary amines, the
expected amine product was mainly obtained (entries 1–4, Table
4). However, with cyclohexylamine and aniline (entries 5–6, Table
4), ca. 15 – 20% of tertiary amine was formed together with the
expected secondary amine products, due to the highest reactivity
of secondary amines, thus competing with the primary amine
substrates. Modifying the ratio oct-1-ene/aniline (1/0.5, 1/1.5, 1/2),
the selectivity was not improved; as expected, a higher amount of
aniline favored the formation of bis-(octyl)phenyl amine (up to
33%, see Table S6 in the Supporting Information).
Overall, the results reported herein stress the fact that glycerol
enables a Rh-based catalytic system working under molecular
regime, to perform one-pot HAM cascade reaction to reach a
reactivity behavior that was thus far limited to multi-catalytic
8-9]
systems,[5-6,
in particular those based on Rh/Ir bimetallic
catalysts for the synthesis of linear amines.[9]
Experimental Section
General procedure for catalytic hydroaminomethylation. In a stainless
steel reactor vessel (100 mL) were placed the desire amount of
[Rh(acac)(CO)2] and tris(3-sulfophenyl)phosphine trisodium salt (TPPTS)
together with glycerol (2 mL), the selected olefin (1 mmol), the selected
secondary or primary amine (1.5 mmol) and n-dodecane as internal
standard (1 mmol). The reactor was pressurized with the selected
proportion of CO/H2 at the desire pressure, temperature and time. After
the reaction was completed, the reactor vessel was cooled to room
temperature and consecutively depressurized. Products were extracted
with cyclohexane (5 x 3 mL), filtered through a Celite column and analyzed
by gas chromatography to determine conversion and selectivity. Products
were isolated and characterized by 1H and 13C NMR, and MS. The Rh
content of extracted organic products was in the range of 0.01-0.08 ppm
as determined by ICP-AES analyses.
Concerning regioselectivity, the linear isomer was the major
product in all cases, with a maximum l/b ratio of 85/15 (entries 5
and 7, Table 4). Ammonia-based reagents (NH3(aq), NH4OAc)
and
sulfonamide
derivatives
(methylsulfonamide,
p-
tolylsulfonamide) did not react under these reaction conditions.
Unfortunately, di- and trisubstituted alkenes (cyclooctene,
ethyloleate, -pinene, -methylstyrene, 4-octene, limonene) did
not undergo HAM (conversions lower than 20%, see Table S7 in
the Supporting Information).
Synthesis of Rh nanoparticles. In
a
Fisher-Porter bottle,
Furthermore, aryl-substituted alkenes, such as 4-allylanisole (2),
4-chlorostyrene (3) and 4-methoxystyrene (4) showed good to
excellent conversions towards HAM, together with high linear-to-
branched outcomes (entries 7–9, Table 4). These results are
particularly interesting for styrene derivatives, because the
formation of the branched regioisomer in the Rh-catalyzed
hydroformylation step is generally favored;[2a] however, the nature
of ligand and solvent triggers a non-innocent effect on the
regioselectivity, reversing this trend as proven by Zhang’s group;
[Rh(acac)(CO)2] (13.0 mg, 0.05 mmol) and TPPTS (28.5 mg, 0.05 mmol)
were dissolved in 10 mL of glycerol at room temperature under Ar. The
system was then pressurized with 3 bar of H2 and stirred at 80 °C during
18 h. The Fisher-Porter bottle was cooled down to room temperature and
depressurized. The resulting black homogeneous solution of dispersed
nanoparticles was dried under vacuum (0.05 mmHg) at 80 °C for 18 h to
remove volatile organic compounds. The as-prepared Rh nanoparticles
were characterized by TEM (see Figure S7 in the Supporting Information).
they obtained the best linear/branched ratio using
a
tetraphosphorus-based ligand and tert-amyl alcohol as solvent.[25]
5
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Acknowledgements
The Centre National de la Recherche Scientifique (CNRS) and
the Université Toulouse 3 – Paul Sabatier are gratefully
acknowledged for their financial support. The French-Mexican
International Associated Laboratory “Laboratoire de Chimie
Moléculaire avec applications dans les Matériaux et la Catalyse”
(LCMMC) is acknowledged for financial support (project number
69-2018). The work was also supported by PhD fellowships to A.
S. M. (CONACyT) and T. D.-B. (Ministry of Education and
Training of the Socialist Republic of Vietnam and CNRS). The
authors thank Christian Pradel for TEM analyses and Corinne
Routaboul (ICT, Toulouse) for helpful assistance with the infrared
experiments with the ReactIR.
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Keywords: Hydroaminomethylation • Rhodium • Glycerol •
Hydrogen transfer • Rh-catalyzed condensation
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Entry for the Table of Contents
A multitalented monometallic Rh-based catalytic system in glycerol enables tandem hydroaminomethylation reaction under a
molecular regime, via low pressure hydroformylation, Lewis acid-assisted condensation and enamine reduction boosted by hydrogen
transfer.
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