Halide bridged trinuclear rhodium complexes and their inhibiting influence on catalysis

Article abstract of DOI:10.1039/c2cy20591b

The addition of halides to the cationic solvate complexes of the type [Rh(PP)(solvent)₂][anion] leads to the formation of trinuclear μ₃-halide-bridged complexes. The corresponding complexes [Rh ₃(PP)₃(μ₃-X)₂][BF₄] with X = Cl or Br and diphosphines PP Me-DuPHOS, Et-DuPHOS, DIPAMP, t-Bu-BisP* and Tangphos were characterized-in most cases-also by X-ray analysis. By reducing the concentration of the active catalyst, the in situ formation of these μ-halide-bridged multinuclear complexes in catalytic reactions leads to a decrease in activity or even to a total inactivity. The required halides-in most cases chloride-are usually present as impurities in the substrates (also when produced industrially). The extent of deactivation, known from enzyme catalysis as competitive inhibition, depends on several factors: the type of halide, the ratio of stability constants of multinuclear halide complexes and of substrate complexes, and the concentration of halide and substrate in solution. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c2cy20591b

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PAPER
Halide bridged trinuclear rhodium complexes and their
inhibiting influence on catalysis†
Angelika Preetz,a Christina Kohrt,a Antje Meißner,a Siping Wei,a
Hans-Joachim Drexler,a Helmut Buschmannb and Detlef Heller*a
Cite this: Catal. Sci. Technol., 2013,
3, 462
The addition of halides to the cationic solvate complexes of the type [Rh(PP)(solvent)2][anion] leads to
the formation of trinuclear m3-halide-bridged complexes. The corresponding complexes [Rh3(PP)3(m3-
X)2][BF4] with X = Cl or Br and diphosphines PP Me-DuPHOS, Et-DuPHOS, DIPAMP, t-Bu-BisP* and
Tangphos were characterized – in most cases – also by X-ray analysis. By reducing the concentration of
the active catalyst, the in situ formation of these m-halide-bridged multinuclear complexes in catalytic
reactions leads to a decrease in activity or even to a total inactivity. The required halides – in most cases
chloride – are usually present as impurities in the substrates (also when produced industrially). The
extent of deactivation, known from enzyme catalysis as competitive inhibition, depends on several
factors: the type of halide, the ratio of stability constants of multinuclear halide complexes and of
substrate complexes, and the concentration of halide and substrate in solution.
Received 22nd August 2012,
Accepted 21st September 2012
DOI: 10.1039/c2cy20591b
www.rsc.org/catalysis
several complexes with m3-bridging methoxy and/or hydroxy
Introduction
anions were characterized by X-ray analysis.3,5 They share a
The influence of basic additives on the selectivity of rhodium-
complex-catalyzed reactions such as e.g. asymmetric homo-
geneous hydrogenation has often been described in the literature.1
Halpern et al. were the first to succeed in characterizing a
reaction product formed by treatment of a cationic rhodium
complex with a base. The reaction of [Rh(DPPE)(MeOH)2][BF4]
(DPPE = bis(diphenylphosphino)-ethane) with triethylamine
led to the trinuclear complex [Rh3(DPPE)3(m3-OMe)2][BF4]2
Recently, we reported the synthesis and characterization of
further rhodium complexes of this kind.3 Structurally similar
trinuclear rhodium complexes are described in ref. 4. With
ligands Me-DuPhos, DIPAMP, DPPE, DPPP as well as BINAP
common structural motif: the three rhodium centers define a
regular triangle, each is coordinated by one bidentate diphosphine
ligand and they are held in place by two m3-bridging anions.
The P–Rh–P plane is perpendicular to the Rh3 plane, and the
m3-bridging anions are located above and below the Rh3 plane.†
A possible reaction sequence for the irreversible formation of
such trinuclear complexes has been described by Saito et al. for
BINAP as the ligand.5 The base generates an anion from the solvent
which initially reacts with the solvate complex6 to form a dinuclear
complex. In a consecutive step the dinuclear complex reacts with
another solvate complex forming the trinuclear complex.
The rather stable trinuclear Rh(I)-complexes can be applied
as ‘diolefin-free precatalysts’, e.g. in asymmetric homogeneous
hydrogenations although, in such cases, characteristic induction
periods are observed in the corresponding hydrogen consump-
tion curves.3 The trinuclear complexes themselves are in fact
catalytically inactive due to the steric hindrance which hampers
access to the [Rh]3 core. However, hydrogenations of prochiral
olefins with such trinuclear complexes result in the same activity
and selectivity as with the corresponding solvate complex if an
a
¨
¨
Leibniz-Institut fur Katalyse e.V. an der Universitat Rostock,
Albert-Einstein-Straße 29a, 18059, Rostock, Germany.
E-mail: detlef.heller@catalysis.de; Fax: +49 381-1281-51183;
Tel: +49 381-1281-183
b Pharmaconsulting Aachen, Ludwigsallee 21, 052062 Aachen, Germany.
E-mail: h.buschmann@pharma-consulting-aachen.de
† Electronic supplementary information (ESI) available: X-Ray data and experi-
mental procedures. CCDC 883479 for [Rh3(t-Bu-BisP*)3(m3-OH)2][BF4], CCDC
883473 for [Rh3((R,R)-Me-DuPHOS)3(m3-Cl)2][BF4], CCDC 883480 for [Rh3((R,R)-t- acid is added to the reaction mixture, which supports the idea
that the solvate complex is the actual catalytically active species.3
Very interesting and of practical relevance is the fact that
certain substrates can be basic enough to trigger the formation
Bu-BisP*)3(m3-Cl)2][BF4], CCDC 883475 for [Rh2((R,R)-Et-DuPHOS)2(m2-Cl)2], CCDC
883478 for [Rh2((S,S)-Me-DuPHOS)2(m2-Br2)], CCDC 883477 for [Rh3((R,R)-Me-
DuPHOS)3(m3-Br)0,8(m3-Cl)1,2][BF4], CCDC 883474 for [Rh3((R,R)-DIPAMP)3(m3-
Cl)2][BF4] and CCDC 883476 for [Rh3((R)-BINAP)3(m3-Cl)2][BF4]. For ESI and
of such trinuclear complexes. An example is provided by the
prochiral olefin (E)-1-(2-methyl-3-phenylallyl)piperidine: at a
crystallographic data in CIF or other electronic format, see DOI: 10.1039/
c2cy20591b
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substrate to catalyst ratio of 10 already 40% of the overall of the corresponding hydroxo-bridged trinuclear complex is
rhodium complex concentration can be assigned to a trinuclear shown in Fig. 1.
complex as detected by 31P-NMR spectroscopy.3
As already mentioned, certain substrates are basic enough to
Although Saito et al. excluded the possibility of trinuclear trigger the formation of such trinuclear complexes. One further
methoxy-bridged complex formation with BINAP, i.e. [Rh3- example, so far undescribed, is provided by [2-(3-methoxy-
(BINAP)3(m3-OMe)2][ClO4], for steric reasons,5 the question phenyl)-cyclohex-1-enylmethyl]-dimethylamine:10 when this sub-
remains whether such trinuclear complexes might be formed strate is hydrogenated in MeOH with [Rh(DIPAMP)(MeOH)2][BF4]
in the presence of even bulkier anions such as halides. This is at room temperature up to 75% of the rhodium content is
especially important considering the fact that, following substrate unavailable for hydrogenation due to the formation of inactive
synthesis, e.g. of prochiral olefins, halides of alkali metals such as trinuclear complexes, see Fig. S1 (ESI†).
NaCl may remain in the substrate as an impurity due to insufficient
removal during work up – also on an industrial scale. For example,
it could be shown that in the hydrogenation of 1-methylene-
l-Chloro-bridged multinuclear complexes
succinamic acid7 with a rhodium-DuPhos catalyst activity Addition of a solution of NaCl in methanol11 to the solvate
might be increased by a factor of 26 if traces of chloride complex [Rh(Me-DuPHOS)(MeOH)2][BF4]12 in the same solvent
remaining from substrate synthesis were thoroughly removed at room temperature led to the spontaneous formation of a
from the substrate.8 Unfortunately, the findings could not be precipitate which is insoluble even at higher temperatures. The
explained at that time.
isolated solid dissolves in acetone and the corresponding 31P-
Due to the relevance of deactivation phenomena in industrial NMR spectrum in acetone-d6 exhibits two doublets, Fig. 2,
catalytic applications,9 we set out to investigate whether (a) indicative of the presence of two compounds. From a dichloro-
halides may lead to the formation of hitherto unknown trinuclear methane solution of the solid that was layered with diethyl
complexes of the type [Rh3(PP)3(m3-X)2][anion] (PP = diphosphine, ether, crystals of one of the compounds were grown suitable for
X = halide) and if so (b) whether their formation negatively affects X-ray analysis. Surprisingly, the trinuclear m3-chloro-bridged
rhodium catalysed processes.
complex [Rh3(MeDuPHOS)3(m3-Cl)2][BF4] was obtained, its
molecular structure is shown in Fig. 3 (left).
Because of the increased steric demand of chloride in
comparison to the methoxy or hydroxy bridge present in
analogous trinuclear complexes, the trinuclear m3-chloro-
bridged complex possesses longer Rh–Rh and Rh–X (X = Cl or
OMe/OH) bonds and wider X–Rh–X angles. Furthermore, in
comparison to the diolefin complexes [Rh(Me-DuPHOS)-
(COD)][BF4]13 the Rh–P bond is considerably shortened.
The second species present in the isolated solid is the neutral
dinuclear complex [Rh2(Me-DuPHOS)2(m2-Cl)2]. The identity of this
species, initially postulated based on NMR data and as a possible
intermediate in the formation of the trinuclear complex according
to Saito’s hypothesis (Scheme 1), was confirmed by X-ray analysis.14
Hence, the addition of NaCl to [Rh(Me-DuPHOS)-
(MeOH)2][BF4] results in the formation of two complexes, the
cationic trinuclear complex [Rh3(Me-DuPHOS)3(m3-Cl)2][BF4]
(31P{1H}-NMR, d 96.8 ppm, JP–Rh = 203.1 Hz) and the neutral
dinuclear complex [Rh2(Me-DuPHOS)2(m2-Cl)2] (31P{1H}-NMR d
96.5 ppm, JP–Rh = 199.6 Hz). While the first type of complex is
described here for the first time, neutral dinuclear complexes
have been known for some time.
Results and discussion
So far methoxo- or hydroxo-bridged trinuclear complexes have
been reported only with the chiral ligands BINAP, DIPAMP and
Me-DuPhos. By using the ligand t-Bu-BisP* we have successfully
shown that such interesting complexes might be formed also
in the presence of very electron rich ligands: the X-ray structure
To assess whether the formation of both complexes takes
place through a reversible consecutive reaction, the neutral complex
[Rh2(Me-DuPHOS)2(m2-Cl)2] (intermediate in Scheme 1) was treated
with the cationic solvate complex [Rh(Me-DuPHOS)(MeOH)2][BF4]
in a THF–MeOH mixture.15 The 31P-NMR spectrum (Fig. S2, ESI†)
proves that indeed the trinuclear complex is formed, in agreement
with the sequence of equilibria described in Scheme 1. Similar
results are detailed in ref. 4b.
Fig. 1 Molecular structure of the cation of [Rh3(t-Bu-BisP*)3(m3-OH)2][BF4] (only
one of the two cations in the unit cell is shown); ORTEP, 30% probability
ellipsoids. The hydrogen atoms of the ligand were omitted for clarity. Selected
distances [Å] and angles [1]: Rh–Rh 3.074–3.084(2), Rh–P 2.177–2.185(2), Rh–O
2.146–2.163(4), P–Rh–P 85.0–85.2(1), O–Rh–O 68.6–68.9(2). 31P{1H}-NMR
(MeOH-d4): d = 85.1 ppm , JP–Rh = 196.9 Hz.
It is evident that the formation of such trinuclear species
must be taken into account if suitable anions which can act as
bridging ligands are present in solution.
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Fig. 2 31P{1H}-NMR spectrum of the precipitate resulting from the addition of NaCl to [Rh(Me-DuPHOS)(MeOH)2][BF4] dissolved in acetone-d6.
Fig. 3 Molecular structure of the cations of [Rh3((R,R)-Me-DuPHOS)3(m3-Cl)2][BF4] (left) as well as [Rh3((R,R)-t-Bu-BisP*)3(m3-Cl)2][BF4], (right); ORTEP 30% probability
ellipsoids. Hydrogen atoms are omitted for clarity. Selected distances [Å] and angles [1] for [Rh3((R,R)-Me-DuPHOS)3(m3-Cl)2][BF4]/[Rh3((R,R)-t-Bu-BisP*)3(m3-Cl)2][BF4]:
Rh–Rh 3.175–3.275 (2)/3.230–3.267 (2), Rh–P 2.172–2.179 (2)/2.181–2.187 (2), Rh–Cl 2.460–2.478 (4)/2.442–2.475 (4), P–Rh–P 85.4–85.7 (1)/84.9–85.7 (1), Cl–Rh–Cl
81.5–81.6 (1)/80.2–80.7 (1).
Scheme 1 General reaction sequence for the formation of trinuclear m3-halide bridged complexes in agreement with Saito et al.5
The reaction of the DIPAMP solvate complex [Rh(DIPAMP)- complex is formed: [Rh3(DIPAMP)3(m3-Cl)2][BF4] (31P{1H}-NMR
(MeOH-d4)2][BF4]16 with a methanolic NaCl solution also d 72.5 ppm, JP–Rh = 203.5 Hz). Comparison of the 31P-NMR data
leads to a 31P-NMR spectrum which shows two doublets, of the second complex with literature values confirms the
Fig. S3a (ESI†). Unlike the experimental findings observed presence of the neutral dinuclear complex [Rh2(DIPAMP)2(m2-Cl)2]
when the Me-DuPHOS ligand was used, the resulting precipi- (31P{1H}-NMR d 74.7 ppm, JP–Rh = 199.6 Hz) analogous to the
tate can be redissolved at elevated temperature. Upon one formed with Me-DuPhos.14 103Rh-NMR measurements
slow cooling, yellow needles precipitated, which were iso- indicate similar electronic environments in both species
lated and characterized by X-ray analysis, Fig. S4 (ESI†). as well: the corresponding chemical shifts are À144 ppm
Hence, for DIPAMP too the trinuclear m3-chloro-bridged for the trinuclear and À77 ppm for the dinuclear complex.
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In the case of the Me-DuPHOS complexes the corresponding
values are À306 ppm (trinuclear complex) and À280 ppm
(dinuclear complex).
An interesting aspect is the dependence of the ratio of
trinuclear to dinuclear complex on NaCl concentration. For-
mally, for the formation of the trinuclear complex 2 equivalents of
Cl are necessary per 3 Rh i.e. 2/3 Cl per 1 Rh, in the case of the
dinuclear complex it is 2 Cl per 2 Rh. Indeed, the experiment shows
that the share of the dinuclear complex [Rh2(DIPAMP)2(m2-Cl)2]
increases with increasing NaCl concentration, which can be
explained with Scheme 1 in the absence of the solvate complex
(MeOH-d4: d 80.6 ppm, JP–Rh = 208.1 Hz), compare Fig. S3a/b (ESI†).
Transferring the solvate complex [Rh(t-Bu-BisP*)(MeOH-d4)2]-
[BF4]4a into a Young-NMR tube containing solid NaCl leads to a
homogeneous solution and to the 31P-NMR spectrum shown
in Fig. S5 (ESI†). Also in this case the trinuclear complex
[Rh3(t-Bu-BisP*)3(m3-Cl)2][BF4] (86.8 ppm, JP–Rh = 204.5 Hz) is
formed, as well as another so far unknown species (84.6 ppm,
JP–Rh = 199.3 Hz) which is assumedly the dinuclear complex
[Rh2(t-Bu-BisP*)2(m2-Cl)2]. The molecular structure of [Rh3-
(t-Bu-BisP*)3(m3-Cl)2][BF4] is shown in Fig. 3, right.17
Using Tangphos as the ligand, two species are observed in
the 31P-NMR spectrum as well if a solution of NaCl dissolved in
MeOH is added to the solvate complex, Fig. S6 (ESI†). One
species is again the trinuclear complex [Rh3(Tangphos)3(m3-Cl)2]-
[BF4] (120.5 ppm, JP–Rh = 200.9 Hz), its detailed characterization
has been discussed in ref. 18. The hitherto unknown second
species (120.2 ppm, JP–Rh = 198 Hz) is most probably the
corresponding dinuclear complex [Rh2(Tangphos)2(m2-Cl)2].
In contrast to what was observed with Me-DuPHOS,
DIPAMP, t-Bu-BisP* and Tangphos, the addition of a methanolic
solution of NaCl to the BINAP solvate complex [Rh(BINAP)-
(MeOH-d4)2][BF4]6 leads to the formation of only one species,
as the 31P-NMR spectrum of the dry precipitate redissolved in
CH2Cl2-d2 proves. Comparison with published data confirms
that the dinuclear complex [Rh2(BINAP)2(m2-Cl)2] (d 49.6 ppm,
JP–Rh = 195.5 Hz, in CD2Cl2) was formed.14 However, the
trinuclear complex might have formed, but rapidly depleted
from solution because of a shift in equilibrium due to the
crystallization of the dinuclear complex. To verify that indeed
only one species had been formed, the experiment was repeated
in a MeOH–CH2Cl2 mixture as the dinuclear complex [Rh2-
(BINAP)2(m2-Cl)2] is well soluble in CH2Cl2. The 31P-NMR spectrum
(Fig. S7a, ESI†) now shows two doublets. The newly formed species
is most probably the trinuclear cation [Rh3((R)-BINAP)3(m2-Cl)2]+19
which is in good agreement with the dependence of its relative
concentration from that of NaCl, vide supra; if the NaCl concen-
tration increases more dinuclear complex is detected by 31P-NMR,
Fig. S7a/b (ESI†).
Fig. 4 Molecular structure of [Rh2((R,R)-Et-DuPHOS)2(m2-Cl)2]; ORTEP, 30%
probability ellipsoids. Hydrogen atoms are omitted for clarity. Selected distances
[Å] and angles [1]: Rh–Rh 3.308 (1), Rh–P 2.158–2.161 (1), Rh–Cl 2.409–2.435 (1),
P–Rh–P 85.4–86.2 (1), Cl–Rh–Cl 83.7–84.7 (1).
With the ligands Et-DuPHOS and BINAP it is hence shown
for the first time that under certain conditions (MeOH as the
solvent and high chloride concentration) it is possible to form
selectively the neutral m2-chloro-bridged complex by addition of
chloride ions to the corresponding cationic solvate complex
[Rh(PP)(MeOH)2][BF4]. Usually these neutral m2-anion-bridged
dinuclear complexes are formed via ligand exchange, e.g. from
[Rh2(COD)2(m2-Cl)2] and a chelating diphosphine.14
l-Bromo-bridged multinuclear complexes
The synthesis of m-bromo-bridged multinuclear complexes was
investigated with Me-DuPhos and DIPAMP as examples. The
addition of a methanolic solution of NaBr11 to the solvate
complex [Rh(Me-DuPHOS)(MeOH)2][BF4] resulted in a yellow
precipitate. The precipitate was redissolved in CH2Cl2 (31P-NMR
spectrum: Fig. S9, ESI†) and layered with diethyl ether. Single
crystals of both the neutral dinuclear and the cationic trinuclear
complex could be isolated and analyzed by X-ray analysis,
Fig. 5.20
In the case of DIPAMP, after the addition of NaBr to the
solvate complex [Rh(DIPAMP)(MeOH)2][BF4]
a red brown
precipitate was instantly formed. Single crystals suitable for
X-ray analysis, however, could not be isolated. Still, NMR
measurements showed that under the described experimental
conditions only one species was formed. From the NMR
spectroscopic data (1H-NMR, Fig. S10, 31P-NMR, Fig. S11, ESI†)
we can infer that only the neutral dinuclear complex [Rh2-
(DIPAMP)2(m2-Br)2] was formed. The coupling constant in the
31P-NMR spectrum JP–Rh = 198.3 Hz is very similar to the ones of
the m2-chloro-bridged dinuclear complexes of DIPAMP and
Me-DuPHOS (for both 199.6 Hz).
l-Halide-bridged multinuclear complexes: deactivating species
Also in the case of Et-DuPHOS – in analogy to BINAP – only
one species is formed upon the addition of NaCl to the solvate As already mentioned in the introduction, m3-methoxy- and
complex [Rh(Et-DuPHOS)(MeOH)2][BF4].12 The initially formed m3-hydroxy-bridged trinuclear complexes affect the efficiency of
voluminous precipitate crystallized overnight yielding yellow asymmetric hydrogenations as they are not active in hydrogenation.3
crystals of the neutral dinuclear complex [Rh2((R,R)-Et-DuPHOS)2-
To investigate the influence of m-halide-bridged multinuclear
(m2-Cl)2] (d 91.1 ppm, JP–Rh = 199.7 Hz, in THF-d8); the molecular complexes on the catalytic activity, the hydrogenation of methyl-
structure is shown in Fig. 4.
(Z)-a-acetamidocinnamate (mac) and dimethyl itaconate with
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Fig. 5 Molecular structure of [Rh2((S,S)-Me-DuPHOS)2(m2-Br2)] (left) and of the cation in [Rh3((R,R)-Me-DuPHOS)3(m3-Br)0,8(m3-Cl)1,2][BF4] (right); ORTEP,
30% probability ellipsoids. Hydrogen atoms are omitted for clarity. Selected distances [Å] and angles [1] for [Rh2((S,S)-Me-DuPHOS)2(m2-Br2)]/[Rh3((R,R)-
Me-DuPHOS)3(m3-Br)0,8(m3-Cl)1,2][BF4]: Rh–Rh 3.263 (1)/3.221–3.274 (1), Rh–P 2.164–2.172 (1)/2.168–2.176 (1), Rh–Br 2.526–2.572 (1)/2.538–2.571 (8), P–Rh–P
86.0–86.1 (1)/85.4–85.7 (1), Br–Rh–Br 85.1–85.2 (1)/85.2–85.9 (2).
Fig. 6 Hydrogen consumption curves for the hydrogenations of 1.0 mmol
methyl (Z)-a-acetamidocinnamate with 0.01 mmol [Rh(DIPAMP)(MeOH)2][BF4]
under addition of sodium halides: red: without additive; green: 0.1 mmol NaCl,
blue: 0.1 mmol NaBr, gray 0.1 mmol NaI (in each case the sodium halide was put
into a glass ampoule together with the substrate); conditions: 15.0 mL MeOH at
25.0 1C and 1.01 bar overall pressure. For clarity the green, blue and gray curve
are each displayed with a 1 min shift compared with the previous curve.
Fig. 7 Hydrogen consumption for the hydrogenation of 1.0 mmol dimethyl
itaconate with 0.01 mmol [Rh(DIPAMP)(MeOH)2][BF4] under addition of different
sodium halides: red: no additive (88% ee); green: 0.1 mmol NaCl, (82% ee); blue:
0.1 mmol NaBr, (80% ee); in each case the halide was added to the substrate in a
glass ampoule); conditions: each 15.0 mL MeOH at 20.0 1C (due to the fact that at
25.0 1C without additive an influence of diffusion cannot be excluded) and 1.01 bar
overall pressure.
Fig. 6 illustrates the influence of different halides on the test
hydrogenation of mac with the DIPAMP system in methanol.
The enantioselectivity (97%) of all experiments was identical,
the solvate complex [Rh(DIPAMP)(MeOH)2][BF4] was monitored
in the presence of sodium salts (Cl, Br, I).
At a first glimpse hydrogen consumption curves for the
hydrogenation of mac with Rh(DIPAMP)(MeOH)2][BF4]3,21 in in the range of reproducibility. Only with NaI, where a sub-
the presence of NaCl show no effect. A closer look at higher stantial deactivation was observed, the enantioselectivity
conversions, however, unequivocally shows that – if compared dropped to 93%.
With prochiral olefins such as dimethyl itaconate which
form much less stable substrate complexes, a much more
pronounced interference during the hydrogenation is expected.22
In Fig. 7 the hydrogen consumption curves for the hydrogenation
to the reference curve – the deviations towards the end of
hydrogenations become more apparent with increasing NaCl
concentration, Fig. S12 (ESI†). In other words, as the concen-
tration of the chiral olefin drops towards the end of the
hydrogenation the halide successfully competes for the solvate of dimethyl itaconate with [Rh(DIPAMP)(MeOH)2][BF4] after
complex.
addition of NaCl and NaBr (0.1 mmol each) are shown.
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The graph clearly indicates that indeed small amounts of Experimental section
halide are enough to induce significant deactivations. In the
case of NaI, after the addition of 0.1 mmol no consumption of
hydrogen was observed.
The above investigations show that with DIPAMP both the
trinuclear and dinuclear complexes are formed with NaCl and
selectively the dinuclear one with NaBr in MeOH. Instead no
conclusion can be drawn about the exact nature of the multi-
nuclear species formed in the presence of NaI. Only few
examples of m2-iodo bridged dinuclear complexes have been
described in the literature.23
The following example proves how important the formation
of the catalytically inactive trinuclear m3-halide-bridged complex
can be. Treatment of the solvate complex [Rh(DIPAMP)-
(MeOH-d4)2][BF4] with the prochiral olefin ((Z)-3-[1-(dimethyl-
amino)-2-methylpent-2-en-3-yl]phenol),24 Fig. S13 (ESI†) (and
also with its hydrogenation product (3-[(2R,3S)-1-(dimethyl-
amino)-2-methylpentan-3-yl]phenol, Fig. S14 (ESI†)) leads to a
31P-NMR spectrum which shows that almost 34% of the signal
intensity corresponds to the catalytically inactive trinuclear
m3-chloro-bridged complex [Rh3(DIPAMP)3(m3-Cl)2][BF4]. The
complex results from traces of chloride left in the substrate after
its synthesis.
General information
All manipulations were carried out under oxygen- and moisture-
free conditions under argon using standard Schlenk or drybox
techniques.
Diethyl ether was distilled from sodium benzophenone ketyl
immediately prior to use. MeOH was freshly distilled from
Magnesia turnings prior to use, MeOH-d4 from LiAlH4 while
CH2Cl2-d2 were distilled from CaH2. Subsequent removal of
traces of oxygen for both deuterated solvents was carried out of
application of six freeze–thaw cycles. NaCl (99.5%, Merck),
NaBr (> 99% Sigma Aldrich) and NaI (> 99% Fluka) were used
as received.
NMR
31P{1H}, 13C{1H}, 13C DEPT, and 1H NMR spectra were obtained
on a Bruker ARX-300 or ARX-400 spectrometer at 297–298 K and
were referenced internally to the deuterated solvent (13C,
CD2Cl2: dreference = 54 ppm, CD3OD: dreference = 49.2 ppm) or
to protic impurities in the deuterated solvent (1H, CDHCl2:
dreference = 5.31 ppm, CD3OD: dreference = 3.32 ppm). For
chemical shifts in 31P{1H} NMR spectra, 85% H3PO4 was used
as an external standard. The chemical shifts are given in ppm.
X-ray structure determination
Conclusions
Diffraction data were collected on a STOE-IPDS II diffracto-
meter using graphite monochromated Mo-Ka radiation. The
structure was solved by direct methods (SHELXS-97)25 and
refined by full matrix least square techniques against F2
(SHELXL-97).25 XP (Siemens Analytical X-ray Instruments,
Inc.) was used for structure representations.
We have shown for the first time that the addition of halides to the
cationic solvate complexes of the type [Rh(PP)(solvent)2][anion]
leads to the formation of trinuclear m3-halide-bridged complexes.
The corresponding complexes [Rh3(PP)3(m3-X)2][BF4] with X = Cl
or Br and diphosphines PP Me-DuPHOS, Et-DuPHOS, DIPAMP,
t-Bu-BisP* and Tangphos were characterized – in most cases – also
by X-ray analysis.
[Rh3(PP*)3(l3-Cl)2][BF4]
These complexes were obtained by hydrogenation of the
[Rh(PP*)(diolefin)]BF4 complex in MeOH (1 mL) for the, respec-
tively, prehydrogenation time and subsequent removal of
hydrogen gas from the yellow solution by application of three
freeze–thaw cycles. A saturated solution of NaCl in MeOH
was added to the frozen out solvate complex and an orange
(in general) precipitate could be isolated.
Such complexes are formed together with the neutral
m2-halide bridged dinuclear ones. Depending on the steric bulk
of the diphosphine, the m-bridging anion and their solubility,
the dinuclear species is formed selectively and this represents a
new synthesis route to this type of complexes, which are known
from the literature.
The formation of the trinuclear species evidently takes place
through a reversible consecutive reaction from the neutral
dinuclear complexes as the intermediate.
[Rh2(PP*)2(l2-Cl)2]
By reducing the concentration of the active catalyst, the
in situ formation of these m-halide-bridged multinuclear
complexes in catalytic reactions leads to a decrease in activity
or even to a total inactivity. This was proven experimentally in
the case of asymmetric hydrogenation. The required halides –
in most cases chloride – are usually present as impurities in the
substrates (also when produced industrially). The extent of
deactivation, known from enzyme catalysis as competitive
Ligand (PP*) and [Rh2(COD)2(m2-X)2] were dissolved in THF.
At À78 1C the ligand was slowly added to [Rh2(COD)2(m2-X)2]
and the mixture was stirred at room temperature for 2 h.
After adding hexane orange or red crystals were formed.
Acknowledgements
inhibition, depends on several factors: the type of halide, the We thank Prof. X. Zhang (Chiral Quest (Suzhou) Inc.) for
ratio of stability constants of multinuclear halide complexes generously supplying us with the Tangphos ligand. We are
and of substrate complexes, and the concentration of halide much obliged to Cornelia Pribbenow, who carried out the
and substrate in solution.
hydrogenations.
c
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12 A. Preetz, H.-J. Drexler, C. Fischer, Z. Dai, A. Borner,
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15 The dinuclear complex is very soluble in THF, however
scarcely soluble in MeOH. Vice versa, the trinuclear complex
is more soluble in MeOH than in THF.
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17 All attempts to isolate [Rh3(t-Bu-BisP*)3(m3-Cl)2][BF4] from
the reaction of the solvate complex with NaCl failed.
However, we succeeded while trying to isolate the product
complex [Rh(t-Bu-BisP*)(macH2)][BF4] from CH2Cl2: the
hydrogenation product of mac was added to the solvate
MeOH complex. The solvent was removed in vacuo and the
remaining solid was redissolved in CH2Cl2 and layered with
diethyl ether. After a few days single crystals of [Rh3(t-Bu-
BisP*)3(m3-Cl)2][BF4] suitable for X-ray analysis crystallized.
18 C. Kohrt, S. Hansen, H.-J. Drexler, U. Rosenthal, A. Schulz
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19 The molecular structure of the trinuclear complex obtained
in a different way is shown in Fig. S8, ESI†.
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20 The m3-bridges of the trinuclear complex are disordered
(population: 0.6 Cl, 0.4 Br). The only Cl source can be the
solvent CH2Cl2 from which the complex was recrystallized.
Only one of the four possible populations is shown.
21 C. R. Landis and J. Halpern, J. Am. Chem. Soc., 1987, 109,
1746–1754.
22 The asymmetric hydrogenation of dimethyl itaconate as
well as the structure and stability of the catalyst–substrate
complex with the DIPAMP system are described in
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7 From the hydrogenation product the THP ether of the
4-amino-2(R)-methylbutan-1-ol, an important intermediate
towards the receptor antagonist TAK-637, can be
synthesized.
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24 The prochiral olefin (Z)-3-[1-(dimethylamino)-2-methylpent-
2-en-3-yl]phenol is also an important precursor of the new
analgesic drug Tapentadol which is as an open-chain
analogue of Tramadol. The chirality of the new stereogenic
centers is very important for the pharmacological effect. The
(R,R) stereoisomer of Tapentadol is a novel, centrally acting
analgesic with a dual mode of action: m-opioid receptor
(MOR) agonism and norepinephrine reuptake inhibition.
Tapentadol is the first oral centrally acting analgesic to be
approved in 2008 in the United States for more than a
decade. The corresponding (S,S) enantiomer is a very strong
opioid. The (R,S) or (S,R) stereoisomers have no analgesic
effect.
10 [2-(3-Methoxy-phenyl)-cyclohex-1-enylmethyl]-dimethylamine
is a member of a class of 1,2-disubstituded cyclohexene
derivatives which are important intermediates in the
synthesis of pharmaceutically active compounds acting on
the central nervous system. The challenge is the establish-
ment of the desired relative and absolute stereochemistry of
two new stereogenic centers responsible for the pharmaco-
logical effect. [2-(3-Methoxy-phenyl)-cyclohex-1-enylmethyl]-
dimethylamine can be transformed by a stereoselective
hydrogenation to Tramadol, an important analgesic drug
used world-wide.
11 Elemental analysis of a saturated NaCl solution in methanol
showed that in 1.0 mL MeOH ca. 7 mg of NaCl can be
dissolved, which corresponds to 0.12 mmol. 105 mg NaBr
(1.0 mmol) and 496 mg NaI (3.3 mmol) can be dissolved in 25 G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr.,
1.0 mL MeOH.
1997, 64, 112–122.
c
This journal is The Royal Society of Chemistry 2013
468 Catal. Sci. Technol., 2013, 3, 462--468