Directing Selectivity to Aldehydes, Alcohols, or Esters with Diphobane Ligands in Pd-Catalyzed Alkene Carbonylations

Article abstract of DOI:10.1021/acs.organomet.1c00228

Phenylene-bridged diphobane ligands with different substituents (CF3, H, OMe, (OMe)2, tBu) have been synthesized and applied as ligands in palladium-catalyzed carbonylation reactions of various alkenes. The performance of these ligands in terms of selectivity in hydroformylation versus alkoxycarbonylation has been studied using 1-hexene, 1-octene, and methyl pentenoates as substrates, and the results have been compared with the ethylene-bridged diphobane ligand (BCOPE). Hydroformylation of 1-octene in the protic solvent 2-ethyl hexanol results in a competition between hydroformylation and alkoxycarbonylation, whereby the phenylene-bridged ligands, in particular, the trifluoromethylphenylene-bridged diphobane L1 with an electron-withdrawing substituent, lead to ester products via alkoxycarbonylation, whereas BCOPE gives predominantly alcohol products (n-nonanol and isomers) via reductive hydroformylation. The preference of BCOPE for reductive hydroformylation is also seen in the hydroformylation of 1-hexene in diglyme as the solvent, producing heptanol as the major product, whereas phenylene-bridged ligands show much lower activities in this case. The phenylene-bridged ligands show excellent performance in the methoxycarbonylation of 1-octene to methyl nonanoate, significantly better than BCOPE, the opposite trend seen in hydroformylation activity with these ligands. Studies on the hydroformylation of functionalized alkenes such as 4-methyl pentenoate with phenylene-bridged ligands versus BCOPE showed that also in this case, BCOPE directs product selectivity toward alcohols, while phenylene-bridge diphobane L2 favors aldehyde formation. In addition to ligand effects, product selectivities are also determined by the nature and the amount of the acid cocatalyst used, which can affect substrate and aldehyde hydrogenation as well as double bond isomerization.

Full text of DOI:10.1021/acs.organomet.1c00228

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Article
Directing Selectivity to Aldehydes, Alcohols, or Esters with
Diphobane Ligands in Pd-Catalyzed Alkene Carbonylations
Dillon W. P. Tay, James D. Nobbs, Srinivasulu Aitipamula, George J. P. Britovsek,*
and Martin van Meurs*
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ABSTRACT: Phenylene-bridged diphobane ligands with different
t
substituents (CF3, H, OMe, (OMe)2, Bu) have been synthesized
and applied as ligands in palladium-catalyzed carbonylation
reactions of various alkenes. The performance of these ligands in
terms of selectivity in hydroformylation versus alkoxycarbonylation
has been studied using 1-hexene, 1-octene, and methyl pentenoates
as substrates, and the results have been compared with the
ethylene-bridged diphobane ligand (BCOPE). Hydroformylation
of 1-octene in the protic solvent 2-ethyl hexanol results in a
competition between hydroformylation and alkoxycarbonylation,
whereby the phenylene-bridged ligands, in particular, the
trifluoromethylphenylene-bridged diphobane L1 with an electron-
withdrawing substituent, lead to ester products via alkoxycarbony-
lation, whereas BCOPE gives predominantly alcohol products (n-nonanol and isomers) via reductive hydroformylation. The
preference of BCOPE for reductive hydroformylation is also seen in the hydroformylation of 1-hexene in diglyme as the solvent,
producing heptanol as the major product, whereas phenylene-bridged ligands show much lower activities in this case. The
phenylene-bridged ligands show excellent performance in the methoxycarbonylation of 1-octene to methyl nonanoate, significantly
better than BCOPE, the opposite trend seen in hydroformylation activity with these ligands. Studies on the hydroformylation of
functionalized alkenes such as 4-methyl pentenoate with phenylene-bridged ligands versus BCOPE showed that also in this case,
BCOPE directs product selectivity toward alcohols, while phenylene-bridge diphobane L2 favors aldehyde formation. In addition to
ligand effects, product selectivities are also determined by the nature and the amount of the acid cocatalyst used, which can affect
substrate and aldehyde hydrogenation as well as double bond isomerization.
catalyst without degradation becomes a significant chal-
lenge,14,15 and less costly Co-based catalysts still tend to
dominate production, despite their lower activity.16
Hydroformylation and alkoxycarbonylation are mechanisti-
cally closely related, with different nucleophiles (H2 or ROH)
attacking a common acyl intermediate to give either aldehydes
or esters (see Figure 1).9,17 Although the latter process is well-
established for Pd catalysts,18−21 Pd-catalyzed hydroformyla-
tion is comparatively much rarer.7
The direct production of alcohols from olefins, termed
reductive hydroformylation, is desirable for certain applica-
tions.22 For example, Co-based catalysts for reductive hydro-
formylation developed by Shell use 9-phosphabicyclo[3.3.1]-
INTRODUCTION
■
Carbonylation of alkenes is an important process to produce
bulk and fine chemicals. This is exemplified by olefin
hydroformylation, one of the largest applications of homoge-
neously catalyzed reactions in the chemical industry.1,2
Examples of hydroformylation products include butyraldehyde
(75% of global aldehyde use, plasticizer alcohol precursors),
midchain C6−C13 aldehydes (plasticizer alcohol precursors),
and C12−C18 aldehydes (for detergent alcohols). Due to its
scale and commercial importance, hydroformylation has been
investigated extensively by industry and academia, in order to
improve upon current processes and explore its applications to
new products.3
Hydroformylation catalysts are generally based on Group 9
metals, with both Co and Rh being employed industrially.4−6
Other metals, most notably Pd, have also shown some
success,7−12 but Rh-catalyzed hydroformylation is generally
regarded as state-of-the-art owing to its high activity and
regioselectivity.13 However, when it comes to higher boiling
hydroformylation products, the separation of the expensive Rh
Received: April 9, 2021
Published: June 7, 2021
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products. Furthermore, hydroformylation of the functionalized
alkenes methyl 4-pentenoate and methyl 2-pentenoate has
been investigated.35,37,38 These substrates can be prepared
from the methoxycarbonylation of C4 feedstocks39 or from
renewable sources such as unsaturated fatty esters or γ-
valerolactone (GVL).40,41 Hydroformylation products such as
methyl 5-formylpentanoate and methyl 6-hydroxyhexanoate
are of great interest as monomers for the synthesis of
polyamides and poly(hydroxyalkanoates) (PHAs), which are
important biodegradable polymers.42,43
Figure 1. Various carbonylation reactions of olefins.
LIGAND SYNTHESIS
nonane (PhobPR) ligands for the production of detergent
alcohols directly via in situ reduction of the intermediate
aldehyde (see Figure 2).23 A related example is the Co-based
catalyst system containing limonene-derived phosphine ligands
(LimPR) reported by Sasol and their application in reductive
hydroformylation.24−27
■
The synthesis of phenylene-bridged diphobane L2 has been
previously described by Drent and co-workers.44 This
procedure was adapted to synthesize a series of diphobanes
with functionalized aryl bridges with electron-withdrawing
t
(CF3) or electron-donating (MeO, Bu) substituents (Table
1).
a
Table 1. Synthesis of Substituted Aryl-Bridged Diphobanes
Figure 2. Examples of phobane (PhobPH) and related ligands.
Noteworthy in the context of the present work is the Pd-
based catalyst system that uses the bidentate diphobane ligand
BCOPE to perform tandem isomerizing reductive hydro-
formylation of internal olefins to linear alcohols (Figure 2).10
The strained C−P−C bridgehead in phobane and related
ligands affects the p-character of the lone pair orbital, thereby
altering the HOMO energy and modulating σ-donor and π-
acceptor properties of the P donor atom. As a result, these
ligands are generally weaker σ-donors and better π-acceptors.28
Surprisingly few reports of these ligand systems have been
reported,29,30 perhaps in part due to the nontrivial syntheses of
the PhobPH and LimPH precursors, which involve the
reaction of pyrophoric PH3 with 1,5-cyclooctadiene or
limonene, respectively, at elevated temperatures.31,32
A significant drawback of reductive hydroformylation is the
often competing olefin hydrogenation to low-value paraf-
fins.33,34 This becomes even more problematic for higher-value
olefinic substrates with additional functionalities, for example,
alkenoate esters.12,35 Hence, in addition to increasing alcohol
yield and minimizing catalyst loss, a significant focus in the
commercial development of reductive hydroformylation
catalysts has been toward limiting alkene hydrogenation side
reactions.36
In this work, we describe the synthesis and characterization
of a series of phenylene-bridged diphobane ligands with
various substituents on the aryl ring. These ligands have been
evaluated in the Pd-catalyzed hydroformylation of simple
aliphatic as well as functionalized olefins to study the effect of
systematic ligand variation on product selectivity. We have
found that remote modifications of the C2 backbone in these
diphobane ligands can alter product selectivity in Pd-catalyzed
olefin hydroformylation. When conducted in an alcohol
solvent such as 2-ethyl hexanol, the solvent is non-innocent,
resulting in a competition between olefin hydroformylation
and alkoxycarbonylation. Electron-donating substituents favor
reductive hydroformylation to alcohols, while electron-with-
drawing substituents favor alkoxycarbonylation to give ester
b
Ligand
R1
R2
Yield/%
31P/δ (ppm)
L1
L2
L3
L4
L5
L6
CF3
H
OMe
OMe
tBu
H
H
H
OMe
H
47
58
54
33
32
37
−15.7, −16.2
−17.3
−16.7, −18.7
−17.7
−16.7, −18.3
3.8
a
Conditions: Substituted dibromobenzene (1 equiv), [3.3.1]- or
[4.2.1]-phobane HP(C8H14) (2.1 equiv), [Pd(PPh3)4] (0.1 equiv),
1,4-diazabicyclo[2.2.2]octane (5 equiv), xylenes, 140 °C, 72 h.
b
CDCl3.
Pd-catalyzed cross-coupling between secondary phobane,
HP(C8H14), and the corresponding 1,2-dibromobenzene
precursor generated a series of substituted aryl-bridged
diphobanes (Table 1). No diphobane product was obtained
when a nitro-substituted precursor (R1 = H, R2 = NO2) was
used, possibly due to the significant electron-withdrawing
effect of the nitro group deactivating the aryl dihalide toward
Pd-catalyzed cross-coupling.45
31P NMR spectra of L1−L5 revealed chemical shifts
between −16 to −18 ppm (CDCl3), a surprisingly narrow
range but in line with the range of chemical shifts observed for
related 1,2-bis(diphenylphosphino)benzene (−12.7 ppm,
CDCl3)46 and 1,2-bis(diphenylphosphino)-4,5-dimethoxyben-
zene (−12.9 ppm, CDCl3).47 The introduction of a single
OMe substituent on the aryl-bridge to give L3 renders the P
atoms inequivalent. The electron-withdrawing inductive effect
of the OMe substituent in the meta position results in a
deshielding of the P donor, whereas the positive mesomeric
effect of the para OMe substituent leads to an overall shielding
effect (Figure 3).
For dimethoxylated ligand L4, the meta electron-with-
drawing inductive effect appears to balance out the para
electron-donating mesomeric effect due to its symmetrical
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Figure 3. Inductive and resonance effects in L3.
substitution, resulting in a chemical shift very similar to that of
the unsubstituted ligand L2. The electron-withdrawing CF3
group in L1 appears to deshield each P atom proportionate to
the distance between them, resulting in two chemical shifts
both downfield from that of the unsubstituted ligand L2. A
more significant deshielding effect is observed when changing
the [3.3.1]-phobane to [4.2.1]-phobane substituents in L6,
resulting in a downfield shift of more than 20 ppm.
Figure 5. Molecular structure of [Pd(BCOPE)Cl2]. Selected bond
angles (deg) and lengths (Å). P1−Pd1−P2, 85.48(5); P2−C2−C1,
108.7(5); C2−C1−P1, 107.4(5); C2−P2−Pd1, 106.1(2); C1−P1−
Pd1, 106.0(2); C3−P1−C7, 96.4(3); C11−P2−C15, 96.6(3); P1−
Pd1, 2.2840(15); P2−Pd1, 2.2752(15); C1−P1, 1.824(7); C2−P2,
1.834(6); C1−C2, 1.500(9).
PALLADIUM DIPHOBANE COMPLEXES
■
Palladium(II) complexes of L2, L6, and BCOPE have been
prepared by reacting equimolar amounts of the corresponding
diphobane ligand with [Pd(COD)Cl2] in CH2Cl2 at room
temperature to give [Pd(L2)Cl2], [Pd(L6)Cl2], and [Pd-
(BCOPE)Cl2] in excellent yields (Figure 4). The addition of 1
Figure 6. Molecular structure of [Pd(L2)Cl2] complex. Selected bond
angles (deg) and lengths (Å). P1−Pd1−P2, 82.31(3); P2−C2−C1,
115.2(2); C2−C1−P1, 115.5(2); C2−P2−Pd1, 99.93(11); C1−P1−
Pd1, 99.59(11); C7−P1−C11, 95.52(15); C19−P2−C22, 95.95(15);
P1−Pd1, 2.2817(8); P2−Pd1, 2.2484(8); C1−P1, 1.855(3); C2−P2,
1.823(4); C1−C2, 1.405(5).
arrangement by twisting its Cl atoms, with Cl1 being 0.22 Å
and Cl2 being 0.19 Å away from the Pd−P1−P2 plane on
opposite sides. The P−Pd−P bite angles in [Pd(BCOPE)Cl2]
of 85.48(5)° and 84.94(2)°/84.31(2)° for the dinuclear
complex [Pd2(BCOPE)2(μ-Cl)2](O3SCH3)2 are comparable
to those of 84.20(4)° and 84.36(3)° reported for the related
complexes [Pd(BCOPE)(H2O)2](OTf)2 and [Pd(BCOPE)-
(MeOH)2](OTf)2.9,48 Differences in ligand bite angles can
have implications for catalytic performance. Studies into ligand
bite angle effects on catalytic activity and selectivity in
carbonylation catalysis have been reported by van Leeuwen
and co-workers.49−51 The P−Pd−P ligand bite angles in the
phenylene-bridged complexes [Pd(L2)Cl2] and [Pd(L6)Cl2]
were determined as 82.31(3)° and 82.18(2)°, considerably
smaller than 85.48(5)° for [Pd(BCOPE)Cl2]. The rigid
phenylene backbone results in a well-defined “envelope”
conformation with Cs symmetry for the 5-membered chelate
formed between ligand and metal center, giving a P1−C1−
C2−P2 dihedral angle of 5.8° for [Pd(L2)Cl2] and 4.3° for
[Pd(L6)Cl2]. The more flexible ethylene backbone in
[Pd(BCOPE)Cl2] allows twisting into a C2 symmetric “half-
Figure 4. Palladium chloride complexes with diphobane ligands.
equiv of Ag(O3SCH3) to [Pd(BCOPE)Cl2] in CDCl3 removes
one of the chloride ligands and results in a chloro-bridged
dinuclear complex [Pd2(BCOPE)2(μ-Cl)2](O3SCH3)2, which
was also isolated and crystallographically characterized (see
Supporting Information). Their molecular structures, along
with selected bond angles and lengths, are shown in Figures 5
and 6 and in the Supporting Information for [Pd(L6)Cl2] and
[Pd2(BCOPE)2(μ-Cl)2](O3SCH3)2.
All complexes are 4-coordinate in the solid state and adopt
square planar geometries characteristic of d8 metal complexes.
[Pd(BCOPE)Cl2] exhibits C2 symmetry, whereas [Pd(L2)Cl2]
shows Cs symmetry and the square planar geometries are
slightly distorted in different ways. [Pd(L2)Cl2] tends toward a
square pyramidal geometry with Cl1−P1−P2−Cl2 lying within
0.09 Å of the same plane and Pd1 displaced 0.20 Å away from
the plane. [Pd(BCOPE)Cl2] distorts toward a tetrahedral
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a
Table 2. Pd-Catalyzed Carbonylation of 1-Octene
isomerization
hydroformylation
alkoxycarbonylation
b
b
b
b
internal octenes
nonanal sel. %
[lin. %]
nonanol sel. %
2-ethylhexyl nonanoate sel. %
b
c
ligand
L1
L2
L3
L4
conv. %
sel. %
[lin. %]
[lin. %]
chemoselectivity
TON
99
99
99
99
99
99
51
54
55
57
59
35
9 [68]
12 [65]
14 [66]
5 [69]
8 [63]
1 [73]
4 [79]
17 [73]
17 [76]
20 [72]
14 [72]
61 [74]
35 [82]
16 [76]
13 [77]
17 [78]
18 [80]
2 [72]
27/73
65/35
70/30
60/40
55/45
97/3
950
900
900
850
850
L5
BCOPE
1300
a
Conditions: 1-Octene (80.6 mmol), Pd(OAc)2 (0.04 mmol), Ligand (L/Pd = 1.4), CH3SO3H (Acid/Pd = 40), aqueous NaCl solution (NaCl/Pd
= 0.4, 1 mL), 60 bar CO/H2 (1:2), 2-Ethyl hexanol (20 mL), 100 °C, 2 h. Yields were determined via gas chromatography using anisole as an
b
internal standard. Note: Trace amounts nonyl nonanoate and nonanoic acid were detected in all runs. sel.: selectivity = product/all products; lin.:
c
linearity = linear/linear+branched products. chemoselectivity = ratio hydroformylation/alkoxycarbonylation. TON (turnover number) = moles of
carbonylation products/moles of catalyst.
chair” conformation, giving a larger P1−C1−C2−P2 dihedral
angle of 56.7°. Both complexes exhibit similar phobane
geometries, with the quaternary bridgehead atoms held in a
strained position to give C−P−C angles of about 96° for
[3.3.1]-phobane ligands and 93° for [4.2.1]-phobane ligands.
The propylene bridges are folded away from the P atom as
observed in [3.3.1]-phobane, HP(C8H14).28 This restricted
geometry has been proposed as one of the reasons for the
unique properties of phobane-based ligands.52,53
[Pd(BCOPE)2]2+ to the active species [Pd(BCOPE)-
(DMSO)2]2+, as seen previously in studies with related ligand
systems.55
HYDROFORMYLATION VERSUS
ALKOXYCARBONYLATION
■
The ligands L1−L5 have been evaluated in Pd-catalyzed
carbonylation reactions of 1-octene, and the results are
summarized in Table 2. Results obtained with BCOPE have
been included for comparison. The catalysts were formed in
situ via the sequential combination of diphobane ligand,
Pd(OAc)2, CH3SO3H, and aqueous NaCl in 2-ethyl hexanol.
2-Ethyl hexanol, a common industrial solvent,56 was chosen in
order to benchmark previous reports where this solvent was
used.10 As will be shown, the alcohol solvent is non-innocent
and can participate in competing alkoxycarbonylation reactions
to form ester products.
Analysis by 31P NMR spectroscopy in CD2Cl2 solution
shows a singlet at 51.3 ppm for [Pd(BCOPE)Cl2], at 38.2 ppm
for [Pd(L2)Cl2] and 65.1 ppm for [Pd(L6)Cl2]. In d6-DMSO,
a singlet at 70.2 ppm is observed for [Pd(BCOPE)Cl2], most
likely due to the exchange of the chloro ligands for DMSO
ligands.54 Similar chemical shifts have been reported for
[Pd(BCOPE)(MeOH)2](OTf)2 (74 ppm) and [Pd-
(BCOPE)(H2O)2](OTf)2 (73.11 ppm) complexes.9,48
The in situ catalyst system was prepared by combining the
diphobane ligand, Pd(OAc)2 and CH3SO3H. The combination
of diphosphine ligands (P−P) and Pd(OAc)2 generally leads
initially to the formation of the kinetic product, a bis-chelate
complex [Pd(P−P)2]2+, which is catalytically inactive.55 Upon
addition of acid (HX), this bis-chelate complex is slowly
converted to the catalytically active monochelate complex
[Pd(P−P)X2], where X can be the anion derived from HX or a
solvent ligand.48 A mixture of BCOPE and Pd(OAc)2 (ratio
1:1.4) and an excess of CH3SO3H in d6-DMSO at room
temperature showed initially the formation of two species
according to 31P NMR analysis: a singlet at 54.5 ppm assigned
to the bis-chelate complex [Pd(BCOPE)2]2+ and a singlet at
70.2 ppm assigned to the monochelate complex [Pd(BCOPE)-
(DMSO)2]2+ in a ratio of 2:1. This ratio changed after 24 h at
room temperature to 1:3, indicating a slow conversion of
The addition of substoichiometric amounts of NaCl with
respect to Pd has been reported to improve yields and
selectivity toward alcohol products in reductive hydro-
formylation reactions.10 The reason for this halide effect is
believed to involve heterolytic H2 activation during the
hydrogenolysis step of the palladium acyl intermediate. We
briefly explored this NaCl effect in the hydroformylation of 1-
hexene using BCOPE, and we could confirm a promotional
effect with respect to heptanol formation (vide infra). In order
to promote reductive hydroformylation, we used NaCl as an
additive in all our hydroformylation studies.
High conversions were achieved in all runs, but there is a
marked difference in the product distribution obtained with
BCOPE, which predominantly favors alcohols (95% selectiv-
ity), and the aryl-bridged diphobanes L1−L5 that give
significant amounts of both hydroformylation and alkoxycar-
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bonylation products. The unsubstituted L2 ligand gave a
product distribution consisting of similar amounts of nonanal,
nonanol, and 2-ethylhexyl nonanoate esters. With L1, there is a
change in chemoselectivity in favor of alkoxycarbonylation to
give 2-ethylhexyl nonanoate as the major product (73%
selectivity). The electron-withdrawing effect conferred by CF3
appears to bias the mechanism toward alcoholysis, yielding
nearly three times more alkoxycarbonylation than hydro-
formylation products.17
According to the mechanism for alcoholysis proposed by van
Leeuwen and co-workers, deprotonation of a coordinated
alcohol species to form a Pd-alkoxy intermediate is followed by
reductive elimination to yield the ester product (Figure 7).17
Figure 8. Proposed mechanism for Pd-catalyzed reduction of heptanal
to heptanol, adapted from the literature.57
comparison, and the promotional effect of the addition of
NaCl on conversion and product selectivity is seen in the last
two runs in Table 3.
Also in this case, high conversions were achieved in all runs.
Pd black formation was not observed in any of the product
mixtures, indicating catalyst robustness under these reaction
conditions. Hydroformylation activity was in the order
BCOPE > L2−L5 > L1,L6. Comparison of the product
compositions between the aryl-bridged diphobanes L1−L6
and BCOPE show that L1−L6 give more internal hexenes,
while BCOPE favors reductive hydroformylation to heptanol
(89% selectivity). Product linearities were similar (ca. 77%)
across the entire series despite the variety of electron-donating
and electron-withdrawing substituents, suggesting that regio-
selectivity is not determined by electronic effects in this case.
Drent and Budzelaar reported similar findings, showing instead
a direct correlation between Pd-catalyzed hydroformylation
product linearity and ligand steric bulk.58
The diphobanes L2−L5 yielded similar amounts of
hydroformylation products (ca. 60%), while the CF3-
substituted L1 and the [4.2.1]-diphobane ligand L6 were
markedly less active (35−43% hydroformylation product). L1
and L6 also demonstrated poorer reductive hydroformylation
ability compared to L2−L5. The unsubstituted ligand L2,
OMe-substituted L3, and tBu-substituted L5 all showed similar
reductive hydroformylation abilities (ca. 30%). However, for
L4 with two OMe substituents, reductive hydroformylation
activity increased to favor nonanol as the major product (68%
selectivity). These results suggest again that electron-rich
donor ligands and hence a more electron-rich Pd center favor
reductive hydroformylation of olefins to alcohols.
Figure 7. Alcoholysis mechanism adapted from van Leeuwen and co-
workers.17
The CF3 group in L1 draws electron density away from the
P donors and consequently results in a more electrophilic Pd
center. This in turn should polarize the O−H bond of a
coordinated 2-ethyl hexanol ligand, facilitate its deprotonation,
and accelerate the alcoholysis of the Pd-acyl species to favor
the formation of 2-ethylhexyl esters. When an electron-
donating OMe substituent is introduced in L3, there is no
significant impact upon product selectivity compared to L2. It
is only upon the introduction of a second OMe group in L4
that an increase in reductive hydroformylation activity is
observed.
Zhou and co-workers have proposed a mechanism for the
homogeneous Pd-catalyzed reduction of aldehydes to alcohols
(Figure 8).57 In the proposed mechanism, Pd-hydride attacks
the carbonyl group in heptanal to give a Pd-alkoxy species that
is protonated by CH3SO3H to yield the heptanol product. An
increase in electron density at the P donor atoms and, hence, at
the Pd center may facilitate this process by increasing the
nucleophilicity of the hydride ligand in the Pd-hydride
complex. If the nucleophilic attack of Pd-hydride on heptanal
is rate-determining, reductive hydroformylation activity would
then directly correlate with electron density, and more
electron-rich ligands such as L4 and BCOPE should yield
more alcohol product, which is indeed observed.
1-HEXENE HYDROFORMYLATION
1-OCTENE METHOXYCARBONYLATION
■
■
The series of aryl-bridged diphobane ligands L1−L6 has been
evaluated in Pd-catalyzed hydroformylation of 1-hexene in the
aprotic solvent diglyme, which avoids competing alkoxycarbo-
nylation, and the results are summarized in Table 3. The
catalysts were formed in situ by the sequential combination of
diphobane ligand, Pd(OAc)2, CH3SO3H, and aqueous NaCl in
diglyme. Results obtained with BCOPE have been included for
The series of aryl-bridged diphobane ligands L1−L5 has been
evaluated for Pd-catalyzed methoxycarbonylation of 1-octene
and the results obtained are summarized in Table 4. Results
obtained with BCOPE have been included for comparison.
Methoxycarbonylation activity follows the order L1 > L2 −
L5 > BCOPE. In contrast to the excellent performance in Pd-
catalyzed 1-hexene reductive hydroformylation (89% heptanol,
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a
Table 3. Pd-Catalyzed Hydroformylation of 1-Hexene
b
b
b
c
d
ligand
L1
L2
L3
L4
L5
L6
BCOPE
BCOPE
conv. %
internal hexenes sel. %
heptanal sel. % [lin. %]
heptanol sel. % [lin. %]
chemosel. al/ol
TON
98
100
100
100
100
100
100
95
55
40
34
38
38
65
5
38 [77]
42 [75]
45 [75]
19 [69]
40 [72]
34 [69]
4 [81]
5 [82]
16 [78]
19 [79]
41 [76]
20 [77]
1 [71]
88/12
72/28
70/30
32/68
67/33
97/3
850
1150
1200
1300
1200
700
89 [78]
52 [68]
4/96
5/95
1850
1050
e
45
3 [84]
a
Conditions: 1-Hexene (161 mmol), Pd(OAc)2 (0.05 mol %), Ligand (L/Pd = 1.4), CH3SO3H (Acid/Pd = 40), aqueous NaCl solution (NaCl/Pd
= 0.4, 1 mL), 60 bar CO/H2 (1:2), diglyme (60 mL), and 100 °C, 2 h. Yields were determined via gas chromatography using anisole as internal
b
c
standard. sel.: selectivity = product/all products; lin.: linearity = linear/linear+branched products. chemosel.: chemoselectivity = ratio
d
hydroformylation/reductive hydroformylation = heptanal/heptanol. TON (turnover number) = moles of heptanal and heptanol/moles of catalyst.
Note: trace amounts of C13 ketones and heptanoic acids were detected in all runs. No NaCl added.
e
a
Table 3), BCOPE demonstrates poor methoxycarbonylation
activity. Olefin isomerization appears to be facile in all cases,
with the majority of the starting substrate 1-octene isomerizing
to a thermodynamic distribution of internal olefins with a 1:49
ratio of 1-octene:internal octenes.59 As previously observed in
Table 2, L1 possessing the electron-withdrawing CF3
substituent exhibits the greatest activity of the diphobane
ligand series for Pd-catalyzed olefin alkoxycarbonylation (56%
methyl nonanoate).
Table 4. Pd-Catalyzed Methoxycarbonylation of 1-Octene
We also investigated briefly the effect of the addition of
aqueous NaCl on the methoxycarbonylation performance of
L2. As can be seen in Table 4, the addition of aqueous NaCl
does lead to fewer internal olefins and an improved yield of
methyl nonanoate from 12% to 35%. However, even better
results were obtained when only water was added, although the
mole balance was incomplete in this case, possibly due to some
additional hydroxycarbonylation or hydrogenation activity.
Catalytic improvement in methoxycarbonylation reactions
upon addition of small amounts of water has been reported
previously.60
b
internal octenes methyl nonanoate sel. %
c
ligand
L1
L2
L3
L4
conv. %
sel. %
[lin. %]
TON
98
98
99
99
99
100
99
99
42
82
87
84
84
96
62
35
56 [73]
16 [74]
12 [76]
15 [77]
15 [76]
3 [77]
1150
300
250
300
300
50
HYDROFORMYLATION OF METHYL PENTENOATE
■
Reductive hydroformylation of the functionalized alkene
methyl 4-pentenoate was investigated next. These studies
follow on from previous work by some of us on the Pd-
catalyzed hydroxycarbonylation of methyl pentenoic acid
mixtures to bioadipic acid.61 Similar reaction conditions were
employed here, using diglyme as the solvent and methane
sulfonic acid (MSA) or trifluoroacetic acid (TFA) as the
cocatalyst. L2 and BCOPE have been compared using both
methyl 4-pentenoate (M4P) and methyl 2-pentenoate (M2P)
as the substrate, and the results are summarized in Table 5.
Initial attempts with M4P and excess methanesulfonic acid
(MSA/Pd = 40, Table 5) gave near-quantitative conversions
with both BCOPE and L2. When BCOPE was employed, 54%
of the undesired hydrogenated olefin product (methyl
L5
BCOPE
d
L2
35 [75]
55 [73]
700
1100
e
L2
a
Conditions: 1-Octene (80.6 mmol), Pd(OAc)2 (0.05 mol%), Ligand
(L/Pd = 1.4), CH3SO3H (Acid/Pd = 40), 50 bar CO, MeOH (20
mL), 100 °C, 2 h. Yields were determined via gas chromatography
using anisole as an internal standard. selectivity = product/all
products. lin.: linearity = linear/linear+branched products. TON
(turnover number) = moles of methyl nonanoate/moles of catalyst.
With addition of aqueous NaCl solution (NaCl/Pd = 0.4, 1 mL).
b
c
d
e
With addition of water (1 mL).
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a
Table 5. Pd-Catalyzed Hydroformylation of Methyl Pentenoate
b
b
bc
,
methyl valerate
sel. %
aldehyde sel. %
alcohol sel. %
[lin. %]
d
substrate
ligand
BCOPE MSA (40 equiv)
L2 MSA (40 equiv)
BCOPE MSA (4 equiv)
L2 MSA (4 equiv)
BCOPE TFA (40 equiv)
L2 TFA (40 equiv)
BCOPE TFA (40 equiv)
L2 TFA (40 equiv)
acid (w.r.t. Pd) conv. % M2P % M3P % M4P %
[lin. %]
TON
e
M4P
M4P
M4P
M4P
M4P
M4P
M2P
M2P
100
99
0
4
9
0
3
3
0
<1
1
54
5
11
<1
1
<1
10
2
0
32 [71]
75 [74]
68 [63]
4 [80]
3 [72]
1 [76]
2 [43]
0
650
1450
1550
1500
1000
950
f
3 [79]
8 [76]
70 [79]
47 [79]
47 [82]
23 [73]
1
99
92
99
60
48
5
1
18
1
52
95
16
30
10
12
2
8
1
40
1
<1
500
<10
a
Conditions: Methyl pentenoate (40.3 mmol), Pd(OAc)2 (0.05 mol %), Ligand (L/Pd = 1.4), 60 bar CO/H2 (1:2), diglyme, 100 °C, 4 h. Yields
b
were determined via gas chromatography using anisole as internal standard. sel.: selectivity = product/all products; lin.: linearity = linear/branched
product. Inclusive of ε-caprolactone. TON (turnover number) = moles of aldehyde and alcohol/moles of catalyst. Suspected ketone or alcohol
derivative side-products (14%). Dimethyl adipate (7%) detected. w.r.t. = with respect to. MSA = methanesulfonic acid. TFA = trifluoroacetic acid.
c
d
e
f
valerate) was obtained together with only 32% of the desired
alcohol. In contrast, the run employing L2 gave significantly
less methyl valerate (5%) and a much greater proportion of
alcohol (75%). Decreasing the amount of MSA from 40 to 4
equiv with respect to Pd lowered olefin hydrogenation even
further to 11% and <1% methyl valerate in the runs using
BCOPE and L2, respectively. These results suggest that MSA
plays an active role in the catalytic cycle to influence olefin
hydrogenation, instead of simply acting as a spectator
counterion. Beller and co-workers demonstrated previously
that the identity and concentration of the acid cocatalyst can
affect catalytic activity and linear selectivity in Pd-catalyzed
olefin hydroformylation.62 Drent and Budzelaar also demon-
strated that varying the acid cocatalyst can affect product
selectivity in Pd-catalyzed olefin hydroformylation reactions.58
At MSA/[Pd] = 4, a remarkable difference in product
selectivity is observed. BCOPE primarily favors reductive
hydroformylation to alcohols (68% selectivity), but L2 favors
aldehyde (70% selectivity) instead. This is in line with our
prior observations in the hydroformylation of 1-hexene (Table
3), where BCOPE favored reductive hydroformylation of 1-
hexene to heptanol.
Changing from MSA (pKa = −1.86) to the less acidic
trifluoroacetic acid (TFA, pKa = 0.23) as the acid cocatalyst
(TFA/[Pd] = 40, Table 5), both BCOPE and L2 yield similar
amounts of aldehyde (47%) and minor amounts of methyl
valerate or alcohol, although the conversion in the case of L2
was significantly lower at 60% versus 99% for BCOPE. There
appears to be a significant role played by the acid cocatalyst in
the hydrogenation of both the starting olefin substrate and the
in situ generated aldehyde intermediate. Furthermore, the
isomerization ability of the two ligands appears to be different.
BCOPE demonstrated facile isomerization of M4P to its
internal isomers, leaving only 1% of the starting M4P in the
final product mixture, whereas with L2, 40% of the starting
M4P was found in the final product mixture. This difference in
isomerization ability is also seen when the internal olefin M2P
is used as the substrate. BCOPE gave 48% conversion in this
case (23% aldehyde), whereas L2 was essentially inactive,
leaving most of the starting M2P (95%) unreacted. The poorer
isomerizing ability of L2 to convert M2P to the more reactive
substrate M4P is likely responsible for this observed lack of
reactivity.
Drent and co-workers noted previously that ligand steric
bulk affects catalytic activity in the Pd-catalyzed hydro-
formylation of internal olefins.10 Bulkier ligands give a more
congested coordination sphere at the metal center, which is
expected to hinder the formation of sterically demanding
branched Pd-alkyl intermediates from the insertion of internal
olefin substrates. We have determined ligand steric bulk by
measuring the amount of space occupied by each ligand in a
sphere of a given radius around the Pd center (i.e., the “ligand
buried volume”).63,64 BCOPE shows a smaller ligand buried
volume (36.3%) compared to L2 (37.2%), which may explain
its greater isomerization ability (see Supporting Information
for details on ligand buried volume calculations).
The distribution of methyl pentenoate isomers in the
product mixtures for L2 (MSA/[Pd] = 4, Table 5) and
BCOPE (TFA/[Pd] = 40, Table 5) favored M3P, although the
conjugated ester M2P is the thermodynamically most stable
product.35 The Pd-alkyl precursors to M3P are likely to be
stabilized by 5- or 6-membered chelates as shown in Figure 9,
which would result in M3P as the kinetically preferred
isomerization product. Such chelates have been proposed
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Hydrogenolysis with H2 results in aldehydes (hydro-
formylation), whereas alcoholysis with MeOH yields esters
(methoxycarbonylation). As a third alternative, a second
methyl pentenoate molecule can coordinate and insert into
the Pd-acyl species to give a secondary Pd-alkyl intermediate
(hydroacylation). This Pd-alkyl intermediate can undergo
hydrogenolysis with H2 to give a saturated ketone or perform
β-hydride elimination to yield an unsaturated ketone.10,58
Indeed, aside from the aldehyde and alcohol products obtained
with BCOPE (MSA/[Pd] = 40, Table 5), for example, smaller
amounts of side products with higher molecular weight were
observed by GC analysis. Further analysis by GC/MS
indicated the formation of ketone side products, but their
exact identity could not be established (see Supporting
Information for details). Since M4P can insert in a 1,2- or
2,1-fashion, or isomerize to M2P/M3P prior to insertion,
several structural isomeric ketones can be obtained (Figure
11). Formation of ketone side products in Pd-catalyzed
hydroformylation has been observed previously using 1-
pentene as the substrate.65 Interestingly, the selectivity of
aldehyde versus ketone products was affected by the nature of
the acid cocatalyst. When trifluoroacetic acid was replaced with
the more acidic trifluoromethanesulfonic acid as the cocatalyst,
more ketone side products were observed, which was ascribed
to the weakly coordinating ability of trifluoroacetate versus the
noncoordinating triflate anion.
Figure 9. Five- and six-membered Pd-alkyl chelate.
previously in our study on Pd-catalyzed hydroxycarbonylation
of pentenoic acids, where a similarly unexpected preference for
isomerization to the 3-position was observed.61
SIDE PRODUCTS − MECHANISTIC
CONSIDERATIONS
■
The mechanism for Pd-catalyzed alkene carbonylation is
assumed to proceed according to the catalytic cycle shown in
Figure 10.58 M4P coordinates to a cationic Pd-hydride
complex before undergoing migratory insertion to give a Pd-
alkyl intermediate. Subsequent coordination and migratory
insertion of CO yields the key Pd-acyl intermediate from
which several different products can be derived.
Figure 10. Competing mechanistic pathways in Pd-catalyzed alkene hydroformylation.
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Figure 11. Possible ketone products derived from the linear Pd-acyl intermediate in Pd-catalyzed hydroformylation of methyl 4-pentenoate.
Other side products can arise from the alcohol products
produced via reductive hydroformylation of methyl pente-
noate. For example, methyl 6-hydroxyhexanoate could react
further in four main pathways as shown in Figure 12: (a) as
intramolecular ring-closing reaction to form caprolactone.
MeOH and caprolactone were indeed observed by GC/MS
analysis and are most likely formed from such trans-
esterification and cyclization reactions. In order to revert
these various derivatives of the alcohol product back to methyl
6-hydroxyhexanoate (and isomers), the product mixtures were
refluxed in MeOH overnight before GC analysis. Some of the
MeOH produced may also engage in methoxycarbonylation
and 7% dimethyl adipate was indeed observed for L2 (MSA/
[Pd] = 4, Table 5). Drent and co-workers were able to
circumvent this issue by using MeOH as a cosolvent in order
to out-compete the alcohol product in side reactions (b) and
(d).12 This, however, may lead to methoxycarbonylation in
addition to hydroformylation. It is clear from the study that
these side reactions in Pd-catalyzed hydroformylation result in
complications which make comprehensive analysis of the
product mixture rather difficult. Further studies are underway
to address these challenges.
CONCLUSIONS
■
A series of substituted aryl-bridged diphobane ligands L1−L5
have been prepared. Crystallographic analyses of the palladium
dichloride complexes have shown some differences in their
coordination compared to the ethylene-bridged BCOPE
ligand. The rigid bridge in [Pd(L2)Cl2] enforces a constrained
geometry that results in a smaller P−Pd−P ligand bite angle of
82° compared to 85° found in [Pd(BCOPE)Cl2]. Perhaps
more important than the change in bite angle is the change in
symmetry, with [Pd(BCOPE)Cl2] showing C2 symmetry,
whereas [Pd(L2)Cl2] has Cs symmetry.
Figure 12. Possible alcohol-derived side reactions: (a) alcoholysis, (b)
transesterification, (c) hemiacetal formation, and (d) cyclization.
The ligands L1−L5 have been applied in Pd-catalyzed
hydroformylation of 1-octene in the presence of 2-ethyl
hexanol solvent. The solvent is non-innocent, resulting in a
competition between hydroformylation and alkoxycarbonyla-
tion. BCOPE directs product selectivity to nonanol (97%
selectivity), whereas L1−L5 give a mix of nonanal, nonanol,
and nonanoate esters. Electron-withdrawing CF3-substituted
L1 favored alkoxycarbonylation to esters (73% selectivity).
The preference for alkoxycarbonylation by electrophilic Pd
centers may be related to the deprotonation of a coordinated
alcohol species to generate Pd-alkoxy complexes that can
reductively eliminate ester products.
ROH in the alcoholysis of Pd-acyl intermediates, (b) in
transesterification with methyl esters to release MeOH, (c) as
ROH in hemiacetal formation to release H2O, and (d) in
intramolecular cyclization to form caprolactone.
Quantification of the desired alcohol product, methyl 6-
hydroxyhexanoate, is therefore complicated by the various
possible side reactions. In Figure 12 reaction (a), the alcohol
product can engage in alcoholysis to give an ester. In reaction
(b), the alcohol product can attack itself or other methyl esters
present such as methyl 4-pentenoate to produce oligomeric
esters. In reaction (d), the alcohol product can undergo an
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The Pd-catalyzed hydroformylation of 1-hexene in diglyme
gave an activity order of BCOPE > L2−L5 > L1. BCOPE
predominantly favored reductive hydroformylation to heptanol
(89% selectivity), whereas L1−L5 gave mixtures of heptanal
and heptanol products, whereby the dimethoxy-substituted L4
favored reductive hydroformylation activity to heptanol.
Electron-donating groups give rise to more electron-rich Pd
centers that can facilitate the nucleophilic attack of Pd-hydride
on in situ generated aldehydes to yield alcohols. Similar linear
selectivity (ca. 77%) across the series, despite the variety of
substituents, suggests that regioselectivity is not significantly
influenced by electronic effects, but is more likely a result of
sterics.
Island, Singapore 627833; orcid.org/0000-0002-8816-
3458; Email: martin_meurs@ices.a-star.edu.sg
Authors
Dillon W. P. Tay − Institute of Chemical and Engineering
Sciences, Agency for Science, Technology and Research, Jurong
Island, Singapore 627833
James D. Nobbs − Institute of Chemical and Engineering
Sciences, Agency for Science, Technology and Research, Jurong
Island, Singapore 627833; orcid.org/0000-0002-4237-
2772
Srinivasulu Aitipamula − Institute of Chemical and
Engineering Sciences, Agency for Science, Technology and
Research, Jurong Island, Singapore 627833; orcid.org/
0000-0001-7640-9513
For Pd-catalyzed methoxycarbonylation of 1-octene, the
activity observed was in the order L1 > L2−L5 > BCOPE,
which was the inverse of that observed for 1-octene
hydroformylation.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.organomet.1c00228
Comparison of BCOPE and L2 in Pd-catalyzed hydro-
formylation of the functionalized olefin 4-methyl pentenoate
revealed that the nature and the amount of acid cocatalyst play
a significant role in olefin and aldehyde hydrogenation activity.
The use of L2 resulted in a decrease in hydrogenation activity,
yielding less hydrogenated byproduct (methyl valerate), and
the main carbonylation product was the aldehyde (95%) when
TFA was used. Increased olefin isomerization was observed for
BCOPE compared to L2, which may be attributed to the less
congested coordination sphere that allows for the formation of
sterically demanding branched Pd-alkyl intermediates. As a
result, BCOPE was found to be more active than L2 in Pd-
catalyzed hydroformylation of the internal olefin 2-methyl
pentenoate (M2P).
These investigations indicate that remote ligand modifica-
tions such as the backbone variation investigated here can have
significant implications on product selectivity. The application
of such ligand modifications in the lesser established field of
Pd-catalyzed hydroformylation can serve to provide insight and
inform future efforts in the development of such catalytic
systems.
Author Contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the Agency for Science, Technol-
ogy and Research (A*STAR) for the funding of this research.
We thank Rhodia (now Solvay) for the donation of Phobane
(PhobPH). We thank Dr. Martin Schreyer for help with XRD
analysis.
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* Supporting Information
The Supporting Information is available free of charge at
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■
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