Rhodium/tris-binaphthyl chiral monophosphite complexes: Efficient catalysts for the hydroformylation of disubstituted aryl olefins

Article abstract of DOI:10.1016/j.jorganchem.2011.10.007

A family of threefold symmetry phosphite ligands, P(O-BIN-OR)₃ (BIN = 2,2′-binaphthyl; R = Me, Bn, CHPh₂, 1-adamantyl), derived from enantiomerically pure (R)-BINOL, was developed. Cone angles within the range 240-270° were calculated for the phosphite ligands, using the computational PM6 Hamiltonian. Their rhodium complexes formed in situ showed remarkable catalytic activity in the hydroformylation of hindered phenylpropenes, under relatively mild reaction conditions, with full chemoselectivity for aldehydes, high regioselectivity, however with low enantioselectivity. The ether substituents at the ligand affected considerably the catalytic activity on the hydroformylation of 1,1- and 1,2-disubstituted aryl olefins. The kinetics of the hydroformylation of trans-1-phenyl-1-propene, using tris[(R)-2′-benzyloxy-1,1′-binaphthyl-2-yl]phosphite as model ligand, was investigated. A first order dependence in the hydroformylation initial rate with respect to substrate and catalyst concentrations was found, as well as a positive order with respect to the partial pressure of H₂, and a slightly negative order with respect to phosphite concentration and CO partial pressure.

Full text of DOI:10.1016/j.jorganchem.2011.10.007

Journal of Organometallic Chemistry 698 (2012) 28e34
Contents lists available at SciVerse ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Rhodium/tris-binaphthyl chiral monophosphite complexes: Efficient catalysts
for the hydroformylation of disubstituted aryl olefins
Rui M.B. Carrilho a, A.C.B. Neves a, Mirtha A.O. Lourenço a, Artur R. Abreu a d, Mário T.S. Rosado a,
**
,
,
a,
*
Paulo E. Abreu a, M. Ermelinda S. Eusébio a, László Kollár b, J. Carles Bayón c , Mariette M. Pereira
a Departamento de Química, Universidade de Coimbra, Rua Larga, 3004-535 Coimbra, Portugal
b Department of Inorganic Chemistry, University of Pécs, Ifjúság u, 6, H-7624 Pécs, Hungary
c Departament de Química, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
d Luzitin S.A., Edifício Bluepharma, Rua Bayer, S. Martinho Bispo, 3045-016 Coimbra, Portugal
a r t i c l e i n f o
a b s t r a c t
A family of threefold symmetry phosphite ligands, P(OeBINeOR)3 (BIN ¼ 2,20-binaphthyl; R ¼ Me, Bn,
CHPh2, 1-adamantyl), derived from enantiomerically pure (R)-BINOL, was developed. Cone angles within
the range 240e270ꢀ were calculated for the phosphite ligands, using the computational PM6 Hamilto-
nian. Their rhodium complexes formed in situ showed remarkable catalytic activity in the hydro-
formylation of hindered phenylpropenes, under relatively mild reaction conditions, with full
chemoselectivity for aldehydes, high regioselectivity, however with low enantioselectivity. The ether
substituents at the ligand affected considerably the catalytic activity on the hydroformylation of 1,1- and
1,2-disubstituted aryl olefins. The kinetics of the hydroformylation of trans-1-phenyl-1-propene, using
tris[(R)-20-benzyloxy-1,10-binaphthyl-2-yl]phosphite as model ligand, was investigated. A first order
dependence in the hydroformylation initial rate with respect to substrate and catalyst concentrations
was found, as well as a positive order with respect to the partial pressure of H2, and a slightly negative
order with respect to phosphite concentration and CO partial pressure.
Article history:
Received 25 July 2011
Received in revised form
28 September 2011
Accepted 5 October 2011
Keywords:
Tris-binaphthyl monophosphite
Cone angle
Rhodium complexes
Hydroformylation
Hindered olefins
Kinetics
Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction
the recent interest in chiral monodentate ligands in asymmetric
catalysis [21e24], there are only a few reports concerning the use of
Hydroformylation is among the most significant CeC bond
forming reactions and represents an important synthetic tool for
the manufacture of aldehydes [1e4]. There is a significant interest
in the catalytic hydroformylation of vinylarenes [5e12], since aryl
alkanals are important intermediates with high synthetic value,
namely in pharmaceutical industry [6,7]. Although it is well known
that the hydroformylation of disubstituted or internal double
bounds is troublesome and usually requires harsh reaction condi-
tions [13], remarkable exceptions are Rh(I)/bulky monophosphite
catalysts that are able to promote the hydroformylation of sterically
hindered substrates, under relatively mild conditions [14e19].
Bulky phosphite ligands proved to enhance rhodium-catalyzed
hydroformylation reaction rates, when compared to rhodium/
phosphine systems [20], due to steric and electronic effects. Despite
chiral monophosphite [25,26] and phosphoramidite [27] ligands in
the asymmetric rhodium-catalyzed hydroformylation. Further-
more, the kinetics and mechanistic studies on catalytic hydro-
formylation are essentially limited to terminal and/or cyclic olefins
[15,16,19,20,28e35]. In fact, the asymmetric hydroformylation of
disubstituted olefins has received much less attention than their
monosubstituted counterparts [8e12]. The synthesis and charac-
terization of C3-symmetric binaphthyl-based chiral mono-
phosphites, of general formula P(OeBINeOR)3 (BIN¼(R)-2,20-
binaphthyl; R ¼ Me, Bn, CHPh2), has been recently developed by
our group [36]. Similar phosphite ligands of type P(OeBINeO2CR)3
(R ¼ Bn, 1-adamantyl) have been also reported, as well as their
efficient application in the asymmetric Rh-catalyzed hydrogenation
of homoallylic alcohols [37].
Herein, we report the synthesis and characterization of a new
monophosphite P(OeBINeOR)3, (R ¼ 1-adamantyl) and the cata-
lytic evaluation of a set of phosphite ligands (R ¼ Me, Bn, CHPh2, 1-
adamantyl) in the asymmetric Rh-catalyzed hydroformylation of
disubstituted aryl olefins, in our endeavour to recognize the effect
of the ligand’s ether substituent in catalysts activity and selectivity.
* Corresponding author. Tel.: þ351239854474; fax: þ351239827703.
** Corresponding author.
E-mail addresses: joancarles.bayon@uab.es (J.C. Bayón), mmpereira@qui.uc.pt
(M.M. Pereira).
0022-328X/$ e see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2011.10.007

R.M.B. Carrilho et al. / Journal of Organometallic Chemistry 698 (2012) 28e34
29
The ligand’s cone angles were calculated using the semi-empirical
PM6 Hamiltonian, and 31P NMR spectroscopic studies in solution
were performed for Rh/phosphite complexes. Furthermore, kinetic
studies were carried out for the hydroformylation of trans-1-
mp: 158e160 ꢀC; [
CDCl3):
a
]
25:ꢁ160 (c 2.0, CH2Cl2). 1H NMR (400 MHz,
D
d
(ppm)]1.32e1.42 (m, 33H), 1.80 (br s, 12H), 6.44 (d,
J ¼ 8.8 Hz, 3H), 6.77 (d, J ¼ 8.4 Hz, 3H), 6.89e7.22 (m, 18H), 7.29 (d,
J ¼ 8.8 Hz, 3H), 7.64 (d, J ¼ 8.4 Hz, 3H), 7.68 (d, J ¼ 7.6 Hz, 3H), 7.70
phenyl-1-propene
with
the
Rh/tris[(R)-20-benzyloxy-1,10-
(d, J ¼ 8.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d (ppm)]29.9, 35.0,
binaphthyl-2-yl]phosphite catalyst, whereas the effects of reaction
parameters in reaction rate and selectivity are discussed.
42.1, 77.7, 119.2, 119.3, 122.3, 122.3, 122.8, 122.9, 123.4, 124.3, 124.5,
124.8, 125.4, 125.5, 126.5, 126.6, 127.1, 127.5, 128.9, 129.0, 132.7,
133.0, 146.7, 146.7, 150.9; 31P NMR (161 MHz, CDCl3):
d (ppm)]
2. Experimental
132.17; HRMS (ESI): (m/z) calcd for C90H81O6PNa [M þ Na]þ,
1311.5663; found, 1311.5628.
2.1. Material and methods
Tris[(S)-20-(benzyloxy)-1,10-binaphthyl-2-yl]phosphite ((S)-4b). The
1H, 13C and 31P NMR spectra were recorded in CDCl3 solutions on
a Bruker Avance 400 MHz spectrometer. Chemical shifts for 1H and
13C are expressed in ppm, relatively to an internal standard of TMS,
while for 31P, a solution of phosphoric acid 85% was used as external
standard. GCeMS was carried out on HP-G1800A mass selective
detector apparatus, equipped with capillary HP-5 column and ESI
detector. GC was carried out on Agilent-6890 and Konik
HRGCe3000C apparatus equipped, respectively, with capillary
product was obtained as a white solid (yield: 87%, 2.315 g); mp:
112e114 ꢀC; [
a
]
25: ꢁ15 (c 1.0, toluene).
D
2.3. General hydroformylation procedure
The autoclave was charged with the appropriate amount of
phosphite (14.5$10ꢁ3 mmol) and the system was purged by three
cycles of vacuum and syngas. A solution of [Rh(CO)2(acac)] (0.75 mg,
2.9$10ꢁ3 mmol) in toluene was introduced, under vacuum. Then, the
reactor was pressurized with 40 bar of an equimolar mixture of CO/
H2, and kept at 80 ꢀC for 1 h to ensure the formation of the Rh/
phosphite complex. After this incubation period, the autoclave was
slowly depressurized and set to the working temperature. The
substrate (2.32 mmol), previously passed through an aluminium
oxide (grade I) column was introduced through the inlet cannula.
Then, pressure was set to the desired value for each catalytic
experiment. For kinetic studies, samples were taken at no more than
20% conversions of alkenes into aldehydes in order to determine the
initial rates, without product interferences. The conversion, chemo-
and regioselectivity throughout the reactions were determined by
gas chromatography analysis of aliquots from the reaction mixture.
Enantiomeric excesses (ee) were determined by GC equipped with
a chiral capillary column, through the injection of the aldehydes or
the respective carboxylic acids obtained from aldehydes oxidation,
with potassium permanganate. Final products of all catalytic reac-
tions were identified by the appropriate analytical techniques.
column HP-5 and chiral capillary column Supelco b-Dex 120, both
with FID detectors. Enantiomerically pure (R)-BINOL (99% ee) and
all reagents were from commercial origin.
2.2. Ligands synthesis
2.2.1. Chiral mono-alkyl ethers
(S) or (R)-BINOL (1) was dried azeotropically with toluene. To
a stirred solution of 1 (5.0 g, 17 mmol), PPh3 (4.5 g, 17 mmol) and
the desired alcohol 2aed (20 mmol) in dry THF (100 mL), diethyl
azodicarboxylate (DEAD) (40% in toluene, 7.5 mL, 17 mmol) was
dropwise added at 0 ꢀC. After 48 h at room temperature, the solvent
was evaporated and the mono-alkyl ethers 3aed were isolated by
silica gel column chromatography, using dichloromethane/n-
hexane (1:1) as eluent, and the products were further purified by
recrystallization from toluene/n-hexane. Spectroscopic data of
3aec were in good agreement with those previously reported [38]
(Note: DEAD is highly toxic, so the appropriate safety proce-
dures were taken for its manipulation. R: 5-11-20-36/37/38-48/20-
63-65-67; S: 26-36/37-62).
2.4. Computational calculation of monophosphite ligand cone
angles
(R)-20-(adamantyloxy)-1,10-binaphthyl-2-ol (3d). The product was
obtained as a white solid (yield: 52%, 3.71 g); mp: 85e87 ꢀC;
In order to measure the monophosphite cone angles, the
MOPAC2009 [39] semi-empirical molecular modelling software and
the molecular editors AVOGADRO [40] and MOLDEN [41] were used.
The first step was the optimization of the monophosphite ligands
4aed molecular geometries for anti conformations, i.e. with the OR
substituents positioned straight opposite to the phosphorus lone
electron pair. After the geometric optimization for a large number of
possibleanticonformers, the most stablewasselected, usingthePM6
semi-empirical Hamiltonian [42] in all calculations. The structure
was then read by the molecular editor, in which a reference point (X)
was defined at a distance of 2.28 Å from the P atom, corresponding to
the centre of the apex angle of Tolman’s [43] cylindrical cone. Since
we were dealing with symmetrical ligands, this point lied along their
C3 axis of symmetry. The farthest H atom from the C3 axis was used to
[
a
]
25: ꢁ130 (c 2.0, CH2Cl2). 1H NMR (400 MHz, CDCl3):
d (ppm)]1.20
D
(d, J ¼ 12.0 Hz, 3H),1.31 (d, J ¼ 12.4 Hz, 3H), 1.46 (br s, 6H), 1.80 (br s,
3H), 5.53 (s, 1H), 6.99 (d, J ¼ 8.4 Hz, 1H), 7.04e7.25 (m, 6H), 7.33 (d,
J ¼ 9.2 Hz, 1H), 7.69e7.76 (m, 4H). 13C NMR (100 MHz, CDCl3):
d
(ppm)]30.9, 35.9, 43.0, 80.6, 117.0, 118.4, 123.1, 123.9, 124.9, 124.9,
125.9, 126.0, 126.4, 126.6, 128.0, 128.2, 129.0, 129.1, 129.5, 129.7,
130.9, 133.8, 133.9, 151.7, 151.9. HRMS (ESI) (m/z): calcd for
C30H28O2Na [M þ Na]þ, 443.1982; found, 443.1988.
2.2.2. Chiral tris-binaphthyl monophosphites
A dried Schlenk flask was charged with the desired monop-
rotected BINOL ether 3aed (6.9 mmol), then placed under nitrogen
atmosphere and dry triethylamine (15 mL) was added. The solution
was cooled to 0 ꢀC and PCl3 (0.2 mL, 2.3 mmol) was slowly added.
After stirring for 3 h, the solvent was evaporated, the phosphites
4aed wereisolated through silica gel column chromatography using
dichloromethane/n-hexane (1:1) as eluent, and further purified by
recrystallization in ethyl ether/n-hexane. Spectroscopic data of 4aec
were in good agreement with those previously reported [36].
measure the P-X-H angles (
convert them into cone angles (
tion [43], considering the van der Waals surfaces, the half cone angle
/2) was calculated by the expression:
a), using the atomic centres. In order to
q), consistent with Tolman’s defini-
(q
q
ð =2Þ ¼
a
þ 180=
p
ꢂ sinꢁ1ðrH=dÞ
(1)
Tris[(R)-20-(adamantyloxy)-1,10-binaphthyl-2-yl]phosphite
4d). The product was obtained as a white solid (yield: 76%, 2.25 g);
((R)-
where rH is the van der Waals radius of hydrogen and d is the
distance XeH [44].

30
R.M.B. Carrilho et al. / Journal of Organometallic Chemistry 698 (2012) 28e34
Scheme 1. Synthesis of tris-binaphthyl monophosphite ligands.
3. Results and discussion
place very slowly to give the BINOL ether 3d in 50% isolated yield.
Therefore, as expected, the nature of the R substituent strongly
affects the rate of etherification. In all cases, the formation of BINOL
bis-ethers was negligible (less than 4%). In the second step of the
synthesis, the phosphorylation of mono-ethers 3aed with PCl3 was
performed in triethylamine, yielding 83%, 81%, 77% and 76% of the
corresponding phosphites, respectively. The use of Et3N as solvent
and, simultaneously, as base in this reaction, rendered clean and
reproducible syntheses.
3.1. Synthesis of chiral tris-binaphthyl monophosphite ligands
The synthetic strategy for chiral monophosphites of general
formula P(OeBINeOR)3, (R ¼ Me, Bn, CHPh2), (R)-4aec has been
previously optimized [36], through the mono-etherification of (R)-
BINOL 1, via modified Mitsunobu reaction [38], using primary and
secondary alcohols, followed by PCl3 phosphorylation (Scheme 1).
In order to expand the study of the effect of the size and structure of
the ligand R group, the monophosphite 4d (R ¼ 1-adamantyl), was
also synthesized following the same approach.
3.2. Ligand cone angles
Reactions of BINOL with methanol 2a or benzyl alcohol 2b, gave
good yields (84e87%) of the desired BINOL mono-ethers 3aeb. The
reaction proceeded at a much slower rate with diphenylmethanol
2c than with primary alcohols, but the mono-ether 3c was obtained
in a satisfactory yield (63%), with full recovery of the non-reacted
BINOL. However, with 1-adamantanol 2d, the etherification took
The cone angles (q) of the new tris-binaphthyl phosphite ligands
were determined, using computational chemistry software and
involving Tolman’s standard definition, as described in section 2.4.
Firstly, the cone angles (q) of trimethyl phosphite P(OMe)3, tri-
phenylphosphite P(OPh)3 and tris(o-tertbutylphenyl)phosphite
P(OeoetBuPh)3 were determined, using the described method-
ology, with the results being consistent with those values previ-
ously reported in the literature [43]. Therefore, the described
Table 1
Calculation of ligand cone angles for optimized anti conformers.
strategy was applied to estimate the cone angles (q) of phosphite
Ligand
Calculated
96ꢀ (107ꢀ)
q (Lit. *)
ligands (R)-4aed, always assuming their anti conformations and
threefold symmetry with P helical orientation [45]. Furthermore, in
the case of ligand (S)-4b, computational calculations were also
performed assuming M helical orientation.
The results in Table 1 show that there is only a slight influence
of the relatively remote OR substituents in the calculated cone
angle for the optimized anti geometries of monophosphite
ligands 4aed, attaining values higher than 200ꢀ in all cases
(239e271ꢀ). In Fig. 1, the front and back views of PM6 optimized
P(OMe)3
P(OPh)3
P(OeoetBuPh)3
(R)-4a
(R)-4b
(S)-4b
123ꢀ (121ꢀ)
188ꢀ (175ꢀ)
239ꢀ
253ꢀ
252ꢀ
(R)-4c
(R)-4d
271ꢀ
249ꢀ
*Literature values [43].
Fig. 1. Front and back views of PM6 optimized structures for monophosphites 4aed anti conformers. a) P(O-BIN-OMe)3; b) P(O-BIN-OBn)3; c) R ¼ P(O-BIN-OCHPh2)3; d) P(O-BIN-
OAdamantyl)3.

R.M.B. Carrilho et al. / Journal of Organometallic Chemistry 698 (2012) 28e34
31
structures for anti conformers of monophosphites 4aed are
illustrated.
Ligands 4a and 4b, with considerable conformational flexibility
on their OR groups, present cone angles of 239 and 253ꢀ, respec-
tively, with the binaphthyl scaffold being the main feature that
determines the ligand cone angle, as it is shown in Fig. 1a and b. The
highly restraining bulkiness of the diphenylmethoxy groups in
ligand 4c push the binaphthyl groups towards the P atom, Fig. 1c,
which causes an increased cone angle of 271ꢀ. The adamantyloxy
groups of monophosphite 4d can easily accommodate opposite to P
atom, with the cone angle (249ꢀ) being also controlled by the
binaphthyl framework.
Scheme 3.
(R ¼ CHPh2). The rates achieved with catalytic systems Rh/4a and
Rh/4b were within those obtained with Rh/4d and Rh/4c. Complete
chemoselectivity was reached for aldehydes, together with
a substrate controlled regioselectivity (ꢄ99% to the linear aldehyde
8), while the stereoselectivity was low (equal or below 15% in all
cases). The Rh/phosphite catalysts were then applied to the
hydroformylation of trans-1-phenyl-1-propene 7, using the same
reaction conditions (Table 2, entries 7e10). From these results, we
observed that the 1,2-disubstituted olefin 7 hydroformylates faster
than the 1,1-disubstituted olefin 6, which is in agreement with the
established relative reactivity of olefins [47], with catalyst Rh/4d
being again the one that achieved the highest rate, with
TOF ¼ 256 hꢁ1; 96% of conversion in 3 h (Table 2, entry 10). The
rates shown for Rh/4aed catalysts followed the same trend for the
substrate 7 (i.e. 4d > 4a z 4b > 4c).
This result becomes evident in Fig. 2 that shows the evolution of
the hydroformylation of 7 along the time, catalyzed with Rh/4aed.
Despite the similar conversions observed using Rh/4c system and
the unmodified Rh catalyst (Table 2, entries 6 and 9) the concom-
itant increased regioselectivity in the presence of the ligand
suggests the formation of a complex with a high sterical hindrance
caused by the diphenylmethoxy groups, which may enclose the
metal, making difficult the olefin approach. Slight differences were
observed in the regioselectivity for 2-phenylbutanal 9 in the range
84e90% with all catalytic systems and, independently of the OR
substituent at the ligand, the enantiomeric excesses were equal or
below 20% (R). As it was expected, the use of phosphite (S)-4b as
ligand in the hydroformylation of 7, produced similar results to
those obtained with its (R)-BINOL based counterpart, however with
3.3. NMR studies of [Rh(acac)(CO)(phosphite)] complexes in
solution
The NMR studies in solution, carried out with equimolar
amounts of [Rh(CO)2(acac)] and phosphites 4aed in CDCl3, at
298 K, revealed in all cases the presence of one major species,
presenting a 31P NMR doublet in the range 120e125 ppm, with
1J(103Rhe31P ¼ 289e292 Hz) attributed to [Rh(acac)(CO)(phos-
phite)] (5aed) (Scheme 2), and a non-identified minor compo-
nent (<10%), showing a doublet in the range
d
¼ 131e134 ppm
and JRhꢁP within 260e265 Hz. When a twofold excess of ligand
was used, the NMR spectra of the complexes remained
unchanged, and only the typical signal of the non-coordinated
phosphite ligand, as a singlet in the range 131e134 ppm, was
observed. Furthermore, when Rh/4a and Rh/4b complexes were
isolated, only the main doublet was observed in the 31P NMR
spectra at 120e125 ppm, a single IR signal at 2005 ꢃ 2 cmꢁ1 was
found, and the exact mass analysis indicated the presence of
rhodium complexes with one carbonyl group and a single phos-
phite ligand, HRMS-ESI [M-acac]þ ¼ 1059.1914 (Rh/4a); [M-
acac]þ ¼ 1287.2882 (Rh/4b). These results are consistent with
those obtained from the previously reported related complex
Rh(acac)(CO)(P(OPh)3) (
d
¼ 122.1 ppm; 1J(103Rh, 31P) ¼ 293 Hz;
IR(CO)
¼
2006 cmꢁ1
)
[46] and the similar Rh/phosphite
complexes of type [Rh(P(OeBINeO2CR)3)(COD)]OTf [37].
3.4. Hydroformylation of hindered phenylpropenes with Rh/chiral
monophosphite catalysts
Table 2
Catalysts prepared in situ from rhodium precursor [Rh(CO)2(a-
cac)] and ligands 4aed, in the presence of syngas, were evaluated in
the hydroformylation of 2-phenyl-1-propene 6 and trans-1-phenyl-
1-propene 7 (Scheme 3).
Table 2 collects the results of the hydroformylation of substrates
6 and 7.
Evaluation of Rh/monophosphite catalysts in hydroformylation of 2-phenyl-1-
propene 6 and trans-1-phenyl-1-propene 7.
Entry
Substrate
Ligand
time
(h)
Conv.a
(%)
TOFb
Regio.
(%)
ee (%)
(hꢁ1
)
1
2
3
4
5
6
no ligand
(R)-4a
(R)-4b
(R)-4c
18
18
18
18
18
41
78
71
47
94
18
35
32
21
42
98c
e
99c
10 (R)e
15 (R)e
8 (R)e
10 (R)e
In the hydroformylation of 2-phenyl-1-propene 6, at 80 ꢀC and
30 bar of syngas, Rh/4aed catalysts reached conversions of 78, 71,
47 and 94%, respectively, after 18 h of reaction, while a conversion
of 41% was obtained without addition of ligand (Table 2, entries
1e5). Thus, a significant ligand effect was observed on the reaction
rates, being the most active catalyst the one with ligand 4d
(R ¼ adamantyl), which was twice as fast as catalyst with ligand 4c
100c
100c
99c
(R)-4d
6
7
8
9
10
11
7
no ligand
(R)-4a
(R)-4b
(R)-4c
(R)-4d
(S)-4b
3
3
3
3
3
3
25
81
72
33
97
74
67
216
192
88
259
197
62d
84d
88d
90d
84d
89d
e
16 (R)f
20 (R)f
11 (R)f
12 (R)f
20 (S)f
Reaction conditions: [Rh(CO)2(acac)] ¼ 0.193 mM, 15 mL toluene; substrate/Rh/
ligand ¼ 800:1:5; P (CO/H2) ¼ 30 bar; T ¼ 80ꢀC.
a
% of substrate converted at the indicated time.
Turnover frequency: mol of substrate converted per mol of Rh per hour.
Regioselectivity: % of 8 with respect to the total amount of aldehydes.
Regioselectivity: % of 9 with respect to the total amount of aldehydes.
% Enantiomeric excesses measured for 8.
% Enantiomeric excesses measured for 9; Chemoselectivity was always ꢄ99% for
b
c
d
e
f
Scheme 2.
aldehydes.

32
R.M.B. Carrilho et al. / Journal of Organometallic Chemistry 698 (2012) 28e34
Table 3
100
80
60
40
20
0
Effect of temperature in the catalytic hydroformylation of trans-1-phenyl-1-propene
7 with Rh/4b
Rh/(R)-4a
Rh/(R)-4d
Rh/(R)-4b
T (ꢀC)
TOFa (hꢁ1
)
Regio.b (%)
50
60
70
80
90
40
144
176
208
232
97
95
91
89
80
Rh/(R)-4c
Reaction conditions: [Rh(CO)2(acac)] ¼ 0.193 mM, 15 mL toluene; 7/Rh ¼ 800, 4b/
Rh ¼ 5; P ¼ 30 bar (CO/H2).
a
Turnover frequency calculated until ca. 20% conversion.
Regioselectivity for 2-phenylbutanal 9. Chemoselectivity was always ꢄ99% for
Rh/no ligand
b
aldehydes.
the occurrence of a required stage for formation/regeneration of the
active catalytic species after the first incubation period, or simply
due to scarce catalytic activity of Rh/4b to carry out the hydro-
formylation of the disubstituted olefin at temperatures below 60 ꢀC.
The regioselectivity for 9 increased from 80 to 97% when the
temperature was diminished from 90 to 50 ꢀC, similar to the results
reported by Lazzaroni et al. [48] in rhodium-carbonyl catalyzed
0
50
100
150
200
250
300
350
time (min)
Fig. 2. Evolution on the hydroformylation of
conditions: [Rh(CO)2(acac)]
P ¼ 30 bar (CO/H2); T ¼ 80 ꢀC.
7
catalyzed by Rh/4aed. Reaction
0.193 mM, 15 mL toluene; 7/Rh/ligand 800:1:5;
¼
¼
hydroformylation of styrene, and attributed to slower b-elimina-
inverse absolute configuration of the products (Table 2, entry 11). In
order to evaluate the catalysts performance in the hydro-
formylation of a terminal aryl olefin, the Rh/4aed catalytic systems
were also applied to styrene. At a temperature of 40 ꢀC and syngas
pressure of 25 bar, regardless of the phosphite used, complete
conversions (>90%) were achieved after 3 h reaction, with TOF’s in
the order of 260 hꢁ1, full chemoselectivity for aldehydes and 96% of
regioselectivity for the branched aldehyde. It should be noticed that
the OR substituent at the ligand did not affect the catalytic activity,
contrarily to the results using substituted olefins as substrates.
Furthermore, using (R)-4b as model ligand, the hydroformylation of
styrene was also performed at 80 ꢀC and 25 bar, achieving complete
conversion after 25 min, with a TOF of 1.9$103 hꢁ1, which is within
the order of the most active catalytic systems reported so far [16].
Despite this remarkable activity, enantiomeric excesses were in the
range 12e20% in all cases. The monodentate nature of the rhodium/
phosphite complexes, as well as the possible equilibrium between P
and M conformations of the ligands in solution [37], which causes
the loss of C3 symmetry and the subsequent chirality, might explain
the low enantiodiscrimination of the catalytic species.
tion. Furthermore, the chemoselectivity was ꢄ99% for aldehydes in
all cases.
The effect of the ligand/Rh molar ratio in the catalyst perfor-
mance was also investigated. The molar ratio was changed from 1
to 20, keeping the rest of parameters in the standard conditions of
this study.
The results summarized in Table 4 indicate that the formation of
the active catalytic species requires from 2.5 to 5 mol of phosphite
per Rh, since in this interval the maximum rate is achieved. Further
increase of the phosphite concentration leads to a drop in the rate.
Remarkably, the regioselectivity for aldehyde 9 scarcely changes
when the phosphite/Rh ratio was increased from 5 to 20. Other
reports of Rh(I) catalysts, modified with naphthyl [18] and biphenyl
[19] based monodentate phosphites, showed a dependence on the
ligand concentration in the reaction rate and selectivity.
The effect of trans-1-phenyl-1-propene concentration on the
rate of the hydroformylation reaction was studied varying the
substrate initial concentration from 38.7 to 309.3 mM, while the
rest of reaction conditions were kept constant. Results are shown in
Fig. 3, where the plot of the TOF versus the initial concentration of
substrate nicely fits with a straight line, indicating that the reaction
is first order with respect to the substrate. Moreover, the chemo-
selectivity for aldehydes was always up to 99% and nearly constant
regioselectivity (88e89%) for 9 was observed in all experiments.
Next, the effect of catalyst concentration on hydroformylation
initial rate was analysed. A substrate concentration of 154.7 mM
was used, keeping constant the standard conditions for this study.
3.5. Kinetic study of hydroformylation of trans-1-phenyl-1-propene
with Rh/4b catalyst
As mentioned above, hydroformylation kinetic studies are
mainly focused on a limited number of model olefins, like styrene
and various terminal linear or cyclic internal alkenes. Nevertheless,
the hydroformylation of disubstituted aryl olefins is actually much
less studied and most of the described catalytic systems require the
use of severe reaction conditions [8e12]. In this context, the olefin
trans-1-phenyl-1-propene 7 was chosen as model substrate and 4b
as model ligand from this threefold symmetry phosphite family, in
order to investigate the effects of the reaction parameters
(temperature, P/Rh ratio, concentrations of substrate and catalyst
and partial pressures of H2 and CO) on the hydroformylation initial
rate and selectivity.
To study the effect of temperature, experiments were performed
in the range 50 to 90 ꢀC, keeping constant the rest of reaction
parameters. Results presented in Table 3 show a sharp increase of
the reaction rate (3.5 times) when the temperature is raised from
50 to 60 ꢀC. Above 60 ꢀC, the rate steadily increases linearly with
temperature. This non-Arrhenius behaviour might be attributed to
Table 4
Effect of 4b/Rh molar ratio in the catalytic hydroformylation of trans-1-phenyl-1-
propene 7.
L/Rh
[ligand] (mM)
TOFa (hꢁ1
)
Regio.b (%)
1
2.5
5
15
20
0.193
0.483
0.965
2.895
3.860
184
216
208
160
144
85
88
89
90
90
Reaction conditions: [Rh(CO)2(acac)] ¼ 0.193 mM, 15 mL toluene; 7/Rh ¼ 800;
P ¼ 30 bar (CO/H2); T ¼ 80 ꢀC.
a
Turnover frequency calculated until ca. 20% conversion.
Regioselectivity for 2-phenylbutanal 9. Chemoselectivity was always ꢄ99% for
b
aldehydes.

R.M.B. Carrilho et al. / Journal of Organometallic Chemistry 698 (2012) 28e34
33
Table 6
Effects of H2 and CO partial pressures on the catalytic hydroformylation of trans-1-
phenyl-1-propene 7 with Rh/4b
400
300
200
100
0
Entry
P(CO) (bar)
P(H2) (bar)
TOFa (hꢁ1
)
Regio.b (%)
1
2
3
4
5
6
7
8
10
10
10
10
20
20
20
20
5
5
10
20
30
2
102
200
376
552
66
112
176
360
277
156
313
340
84
85
88
88
82
88
88
90
81
95
81
86
5
10
20
10
10
20
20
9
10
11
12
25
2
5
Reaction conditions: [Rh(CO)2(acac)]¼0.193mM, 15 mL toluene; 7/Rh¼800, 4b/
Rh¼5; T¼80ꢀC.
0
50
100
150
200
250
300
a
Turnover frequency calculated until ca. 20% conversion.
Regioselectivity for 2-phenylpropanal 9. Chemoselectivity was always ꢄ99% for
b
[
trans-1-phenyl-1-propene] (mM)
aldehydes.
Fig. 3. Effect of the initial substrate concentration on hydroformylation TOF with Rh/
4b. Reaction conditions: [Rh(CO)2(acac)] ¼ 0.193 mM, 15 mL toluene; 4b/Rh ¼ 5;
P ¼ 30 bar (CO/H2); T ¼ 80 ꢀC.
different isomeric aldehydes 9 and 10 formation rates dependence
with p(H2) and p(CO). Thus, considering the experiments involving
p(CO) ¼ 10 bar and varying p(H2) from 10 to 30 bar (Table 6, entries
2e4), as well as p(H2) ¼ 10 bar and varying p(CO) from 10 to 25 bar
(Table 6, entries 2,7 and 10), the experimental rate expression (2)
for the hydroformylation of trans-1-phenyl-1-propene with the Rh/
phosphite 4b catalyst, obtained from the plots of log (TOF) as
function of the several parameters, can be written as:
The results collected in Table 5 show that the reaction is also first
order with respect to the catalyst concentration. Also no consid-
erable changes were observed in regioselectivity with variation of
initial catalyst concentration, while chemoselectivity was always
ꢄ99% for aldehydes.
The effects of CO and H2 partial pressures were then appraised
in the initial rate and selectivity of the reaction, using the Rh/4b
catalyst and the results are summarized in Table 6.
d½aldehydeꢅ=dt ¼ k½Rhꢅ½phosphiteꢅꢁ0:3½substrateꢅ½H2ꢅ½COꢅꢁ0:3
(2)
The results show a linear dependence of the reaction rate with
the partial pressure of H2, for constant partial pressures of CO, at
both 10 and 20 bar (Table 6, entries 1e8). The regioselectivity for
aldehyde 9 does not depend on p(H2) when a partial pressure of CO
of 10 bar is used (Table 6, entries 1e4) however, when a higher
p(CO) of 20 bar is used, an increase from 82 to 90% is observed in
the regioselectivity, varying p(H2) from 2 to 20 bar (Table 6, entries
5e8).
A more complex effect was observed for CO partial pressure on
the reaction rate. At a constant H2 partial pressure of 10 bar, the
increase of p(CO) from 5 to 25 bar produced a decrease in reaction
rates (Table 6, entries 2,7,9,10). At a constant H2 partial pressure of
20 bar, the increase of p(CO) from 2 to 10 bar caused a slight
increase in reaction rates (Table 6, entries 3,11,12), however a slight
decrease in the rate was observed varying CO partial pressure from
10 to 20 bar (Table 6, entries 3 and 8). Moreover, significant increase
in the regioselectivity for aldehyde 9 was observed when p(CO) was
raised, for both H2 partial pressures of 10 and 20 bar (Table 6,
entries 2,7,9,10 and entries 3,8,11,12). Since both H2 and CO partial
pressures have a significant effect in the reaction regioselectivity,
the complex effects depicted in Table 6 may be explained by the
This expression applies exclusively to the standard conditions
used in this study, [Rh] ¼ 0.2e0.6 mM, phosphite/Rh ꢄ 5,
[substrate] ¼ 30e300 mM and CO and H2 pressures ꢄ 10 bar. The
partial negative orders for the CO pressure and ligand, combined
with a positive order with respect to the substrate are reminiscent
of the expressions found for the hydroformylation of 1-alkenes
with Rh/PPh3 catalysts [33e35,49]. However, the most striking
result of the kinetic expression for the hydroformylation of trans-1-
phenyl-1-propene with the Rh/phosphite 4b catalyst is the positive
order for both the substrate and the H2 pressure, suggesting that
either the olefin coordination/insertion or the oxidative addition of
H2 to the Rh/acyl intermediate may be the rate determining step.
This ambiguous behaviour may be attributed to an intermediate
situation, implying that there is not a clear rate limiting step, since
two of more steps proceed at similar rate, or rather due to the
presence of dinuclear metal resting state species, whose fast
equilibrium with the active catalytic species depends on H2 pres-
sure [50e52].
4. Conclusions
Table 5
An efficient and clean two-step synthesis of a family of chiral
bulky monophosphite ligands was developed, and the cone angles
for PM6 optimized anti structures were calculated based on original
Tolman’s definition, achieving values in the range 239e271ꢀ. The
rhodium/phosphite complexes, prepared in situ, showed remark-
able catalytic activity in the hydroformylation of hindered phenyl-
propenes, under relatively mild reaction conditions, with full
chemoselectivity for aldehydes. A significant effect of the ether
substituent R at the ligand was observed in the catalytic activity,
following the trend R ¼ adamantyl > R ¼ Me z R ¼ Bn > R ¼ CHPh2,
when both 1,1- and 1,2-substituted aryl olefins were used as
substrates. Regardless of the ligands’ structure, regioselectivities in
Effect of Rh concentration in the catalytic hydroformylation of trans-1-phenyl-1-
propene 7 with Rh/4b
[Rh(CO)2(acac)] (mM)
Initial ratea (mmol substrate$hꢁ1
)
Regio.b (%)
0.193
0.386
0.580
0.603
1.253
1.810
89
92
91
Reaction conditions: [7] ¼ 154.7 mM, 15 mL toluene; 4b/Rh ¼ 5; P ¼ 30 bar (CO/H2);
T ¼ 80 ꢀC.
a
Initial rate in mmol of substrate converted into aldehydes per hour until ca. 20%
conversion.
b
Regioselectivity for 2-phenylbutanal 9. Chemoselectivity was always ꢄ99% for
aldehydes.

34
R.M.B. Carrilho et al. / Journal of Organometallic Chemistry 698 (2012) 28e34
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