Gem-Dialkyl Effect in Diphosphine Ligands: Synthesis, Coordination Behavior, and Application in Pd-Catalyzed Hydroformylation

Article abstract of DOI:10.1021/acscatal.9b03007

A series of palladium complexes with C₃-bridged bidentate bis(diphenylphosphino)propane ligands with substituents of varying steric bulk at the central carbon have been synthesized. The size of the gem-dialkyl substituents affects the C-C-C bond angles within the ligands and consequently the P-M-P ligand bite angles. A combination of solid-state X-ray diffraction (XRD) and density functional theory (DFT) studies has shown that an increase in substituent size results in a distortion of the 6-membered metal-ligand chair conformation toward a boat conformation, to avoid bond angle strain. The influence of the gem-dialkyl effect on the catalytic performance of the complexes in palladium-catalyzed hydroformylation of 1-octene has been investigated. While hydroformylation activity to nonanal decreases with increasing size of the gem-dialkyl substituents, a change in chemoselectivity toward nonanol via reductive hydroformylation is observed.

Full text of DOI:10.1021/acscatal.9b03007

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Article
The gem-Dialkyl Effect in Diphosphine Ligands: Synthesis, Coordination
Behavior and Application in Pd-catalyzed Hydroformylation
Dillon W. P. Tay, James D. Nobbs, Charles Romain, Andrew J. P. White,
Srinivasulu Aitipamula, Martin van Meurs, and George J.P. Britovsek
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b03007 • Publication Date (Web): 03 Dec 2019
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ACS Catalysis
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The gem-Dialkyl Effect in Diphosphine Ligands: Synthesis,
Coordination Behavior and Application in Pd-catalyzed
Hydroformylation
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Dillon W. P. Tay, James D. Nobbs,† Charles Romain, Andrew J. P. White, Srinivasulu
Aitipamula,† Martin van Meurs,† George J. P. Britovsek.*
Department of Chemistry, Imperial College London, Molecular Sciences Research Hub, White City Campus, 80
Wood Lane, W12 0BZ, United Kingdom. †Institute of Chemical and Engineering Sciences, Agency for Science,
Technology & Research, Jurong Island, Singapore 627833.
ABSTRACT: A series of palladium complexes with C3-bridged bidentate bis(diphenylphosphino)propane ligands with
substituents of varying steric bulk at the central carbon have been synthesized. The size of the gem-dialkyl substituents
affects the C–C–C bond angles within the ligands and consequently the P–M–P ligand bite angles. A combination of solid
state XRD and DFT studies has shown that an increase in substituent size results in a distortion of the 6-membered
metal-ligand chair conformation towards a boat conformation, in order to avoid bond angle strain. The influence of the
gem-dialkyl effect on the catalytic performance of the complexes in palladium-catalysed hydroformylation of 1-octene has
been investigated. While hydroformylation activity to nonanal decreases with increasing size of the gem-dialkyl
substituents,
a change in chemo-selectivity towards nonanol via reductive hydroformylation is observed.
KEYWORDS: Thorpe-Ingold, hydroformylation, gem-dialkyl, chelate, bidentate, diphosphine
phosphines.8 This natural bite angle βn can provide a
1. INTRODUCTION
quantitative measure of the relationship between ligand
backbone structure and catalytic performance. It has been
used to show how ligand bite angles can influence the
catalytic cycle by stabilizing (or destabilizing) initial or
final reaction intermediates and transition states,9
thereby effecting significant changes in catalyst activity
and selectivity.10
Advancements in transition metal co-ordination
chemistry and in understanding organometallic reaction
mechanisms have led to continual improvements in
homogeneous catalyst development.1 Despite the
importance typically placed on the identity of the
transition metal in catalyst design, the characteristics of
the ancillary ligand can be critical for catalyst stability,
controlling reaction rates and determining chemo- and
regioselectivity.2 Ligand -donor and -acceptor
properties influence the electronic environment at the
metal center, while ligand structure and co-ordination
geometry impose steric constraints that affect the spatial
environment. For monodentate phosphines, these steric
and electronic parameters are classically quantified via
the Tolman electronic parameter, χ, and ligand cone
angle, θ.3-5 In the case of bidentate ligands, these
parameters are insufficient to account for the additional
nuances introduced by ligand backbone structure and
bidentate chelation.6-7 In order to capture this, Casey and
Whiteker introduced the concept of natural bite angle,
βn,8 which gives an indication of the preferred chelation
angle determined by ligand backbone rigidity in bidentate
A straightforward way to modify ligand bite angle is to
adjust the length of the ligand backbone, since longer
backbones typically result in larger bite angles, but with
increased flexibility.7 Conversely, a rigid ligand backbone
such as 1,2-phenylene can be employed to enforce a
certain bite angle.11 A less direct and more subtle
modification, which has been investigated here, is to
manipulate the bite angle through gem-dialkyl
substitution at the ligand backbone (see Figure 1).
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corresponding electrophilic precursors with lithium
diphenyl phosphide, as shown in Figure 2.
steric repulsion
1
2
3
4
5
6
7
8


R
R
gem-dialkyl
R
R
R
R
R
R
effect
2 LiPPh2
- 2 LiX
P
P
P
P
R = alkyl
M = metal
X
X
Ph2P
PPh2
M
M
X = leaving group
R = alkyl
Figure 1. The gem-dialkyl effect in diphosphine ligands.
Precursors:
Steric repulsion between geminal alkyl groups (R) can
simultaneously widen the R-C-R  bond angle and
compress the C-C-C  bond angle, thereby indirectly
altering the P-M-P bite angle and the steric environment
around the metal centre. An electronic effect from the
geminal dialkyl groups on the phosphine donors is also
possible, but is expected to be relatively minor compared
to the steric effects, due to the remoteness and weak
electron-donating properties of the alkyl groups. A gem-
dialkyl effect in diphosphine ligands has been observed
previously, for example to modify reaction rates,12-13
regioselectivity14 or substitution behavior.15
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R
R
R
R
R
R
O
O
O
TsO
OTs
X
X
S
X = Cl or Br
O
Type I
(Tosylate)
Type II
(Halide)
Type III
(Cyclic
Sulfate)
R = H, Me, iso-propyl or iso-propyl/iso-pentyl
Figure 2. General synthetic pathway ligands L2-L4.
Three classes of electrophiles were investigated:
tosylates (Type I), halides (Type II) and cyclic sulfates
(Type III). These functionalities were selected for their
weak conjugate basicity implying good leaving group
ability, and in the case of tosylates and cyclic sulfates, for
their ability to activate 1,3-diols toward nucleophilic
substitution.
In organic synthesis, the gem-dialkyl effect, better
known as the Thorpe-Ingold effect, has been known for
over a century to accelerate cyclization reactions by
favoring reactive rotamers and stabilizing ring
structures.16-18 In contrast, there is comparatively little
insight into its role and impact on ligands in coordination
chemistry and
catalysis. As
a
well-established
phenomenon in organic synthesis, previous studies on the
gem-dialkyl effect can provide a basis for predicting how
ligand structure and subsequent co-ordination bahaviour
may be influenced. However, extrapolating to how this
might affect catalytic performance remains non-trivial.
Ph2P
PPh2
Ph2P
PPh2
L1
L2
In this paper, we report the synthesis and
characterization
of
a
series
of
bidentate
bis(diphenylphosphine)propane ligands L1-L4 with
different geminal dialkyl groups at the central carbon of
the ligand backbone (Chart 1). A detailed conformational
analysis of the ligand binding modes, effects on
coordination environment and space around the metal
center has been carried out using structural and
computational techniques. The diphosphine ligands have
been applied in the hydroformylation of 1-alkenes,
arguably one of the most important applications in
homogeneous catalysis.19-20 In the case of Pd-catalyzed
hydroformylation of 1-octene, we show that gem-dialkyl
substitution reduces hydroformylation activity and alters
chemoselectivity to favor reductive hydroformylation.
Reductive hydroformylation, the direct conversion of
Ph2P
PPh2
Ph2P
PPh2
L3
L4
Chart 1. Series of Bidentate Bis(diphenylphosphino)propane
Ligands L1-L4.
Ligand Precursors
Hydrogenation followed by
a
cross-Cannizzaro
reaction with formaldehyde22 yielded asymmetric iso-
propyl/iso-pentyl diol from commercially available 2-
isopropyl-5-methyl-2-hexanal. This was then used to
make precursors 1-3 (see Figure 3).
alkenes
to
alcohols
using
a
combined
hydroformylation/hydrogenation protocol, has seen
renewed interest in recent years.21
(a)
TsCl, Pyridine
2. RESULTS AND DISCUSSION
Synthesis and Characterisation
OTs OTs
OH OH
The synthesis of the ligand series was envisioned to
proceed via SN2 nucleophilic substitution of the
1
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generated lithium diphenyl phosphide and the results are
(b)
(c)
PPh3, Br2
1
2
3
4
5
6
7
8
summarized in Table 1.
Br Br
OH OH
Table 1. Synthesis of gem-Dialkyl Substituted
Bidentate Bis(diphenylphosphino)propane Ligands.
2
R1 R2
(i) nBuLi
(i) Et3N, SOCl2
H-PPh2
2
O
O
O
O
(ii) NaIO4, RuCl3
OH OH
(ii) Electrophile
PPh2 PPh2
S
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3
1
2
1
2
L1
L2
L3
L4
: R = R = H
: R = iPr, R = iPent
1
2
1
2
: R = R = Me
: R = R = iPr
Figure 3. (a) Synthesis of tosylate 1. (b) Synthesis of bromo-
analog 2. (c) Synthesis of cyclic sulfate 3.
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L
Electrophile
R1
R2
Time / h
Yield*
/ %
Both tosylate 1 and cyclic sulfate 3 were prepared via
L2
L2
L3
L3
L4
Type I
Type II (Cl)
Type II (Br)
Type III
Me
Me
iPr
iPr
iPr
Me
Me
24
24
0
96
16
14
11
known procedures,23-25 while bromo-analog
prepared via the Appel reaction.
2
was
iPent
iPent
iPr
72
96
168
O
O
O
O
(i) NaH
(ii)
Type III
EtO
OEt
EtO
OEt
EtO
Conditions: H-PPh2 (2.1 eq), electrophile (1 eq), nBuLi (2.1 eq),
THF, 65 oC. *Isolated yields.
Br
4
The 31P{1H} NMR spectrum of the reaction mixture
from the synthesis of L2 from Type I tosylate precursor
showed a major phosphorus product (ca. 48%) as a singlet
at -15.0 ppm, which suggests Ph2P-PPh2 (literature value26
= -15.2 ppm). No desired product L2 was observed, and
22% of the starting tosylate was recovered. This is
consistent with an earlier report by Eberhard, who
demonstrated that undecorated C3-bridged di-tosylates
could be used to prepare bidentate diphosphine ligands
through treatment with lithium phosphides. However,
upon gem-dimethylation of the central carbon, P-P
bonded species were obtained as major by-products.27
Earlier work by Harris and Pretzer on the synthesis of P-P
diphosphines from alkyl halides reported a proposed
mechanism for the formation of these species.28 In order
to avoid these side reactions, subsequent synthetic efforts
were focused on Type III cyclic sulfate precursors that
did not possess the halide groups that were implicated in
their formation.
O
O
(i) NaH
(ii)
LiAlH4
OEt
Br
OH OH
6
5
Et3N, SOCl2
O
O
O
NaIO4, RuCl3
S
O
7
Figure 4. Synthesis of di-iso-propyl cyclic sulfate 7.
The synthesis of precursor 7 required a different
approach (see Figure 4). The synthesis of di-iso-propyl
malonate 5 required excess isopropyl bromide to go to
completion. This was attributed to deprotonated
malonate 4 acting as a base (E2 mechanism) instead of a
nucleophile (SN2 mechanism) on isopropyl bromide to
give propene because of its sterically hindered tertiary
carbanion. Despite this, 99% conversion to di-iso-propyl
substituted malonate 5 was achieved through repeated
additions of isopropyl bromide in excess. Subsequent
reduction of malonate 5 with LiAlH4 yielded diol 6 that
was then converted to di-iso-propyl cyclic sulfate 7 using
the methodology employed previously for iso-propyl/iso-
pentyl analog 3.
The synthesis of asymmetric iso-propyl/iso-pentyl
ligand L3 from Type III cyclic sulfate precursor gave a
reaction mixture that had a 31P{1H} NMR spectrum
containing L3 as a singlet at -25.3 ppm (ca. 60%) with a
single major by-product as a singlet at -16.3 ppm (ca.
36%). The mixture was protected with BH3, separated via
column chromatography, and deprotected with refluxing
EtOH to give L3 in modest yield (14%).29 A similar
procedure yielded the di-iso-propyl ligand L4 in modest
yield (11%). Subsequent modifications attempting to
improve yield using LiPPh2 with Type II (Br) precursor
resulted in a product mixture with similar 31P signals. This
suggests that the identity of the leaving group does not
play a significant role in the occurring side reaction, and
Diphosphine Ligand Synthesis
The synthesis of ligands L2-L4 was accomplished via
SN2 substitution of the ligand precursors with in-situ
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that it may be a problem with the synthetic strategy in
general. A possible alternative to circumvent this could
involve an Umpolung-type reversal of polarities,
generating di-Grignards from 1,3-dihalides as the
nucleophile to attack chlorophosphine electrophiles
instead.30
Page 4 of 12
R1 R2
R1 R2
PPh2 PPh2
1
1
2
3
4
5
6
7
8
Pd(COD)Cl2
DCM, rt
Ph2P
PPh2
Pd
Cl
Cl
2
L2
R = R = Me, Pd( )Cl2: 97% yield
1
2
L3
R = iPr, R = iPent, Pd( )Cl2: 96% yield
1
2
L4
R = R = iPr, Pd( )Cl2: 99% yield
Palladium Complexes
Figure 5. Synthesis of Pd(L)Cl2 complexes.
The ligands L2-L4 were combined with [Pd(COD)Cl2]
to give the corresponding [Pd(L)Cl2] complexes in
excellent yield (see Figure 5 and Supporting Information
for details). Single crystals suitable for XRD analysis were
grown either via layering of pentane on a DCM solution of
the complex or via slow diffusion of cyclohexane into a
DCM solution of the complex (Figure 6).
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Figure 6. Crystal structures of Pd(L)Cl2 complexes of L2 (left), L3 (middle) and L4 (right) with displacement ellipsoids shown at
50% probability. Hydrogen atoms omitted, and only selected atoms labelled for clarity.
Table 2. Selected Bond Lengths (Å) and Angles (°) of Pd(L)Cl2.a
There is a 2° decrease between L2 and L3 as the  angle
remains essentially the same at the ideal tetrahedral value
of 109.5°. It is noteworthy that despite a lack of change in
 angle between L2 and L3, the gem-dialkyl effect still
Pd(L1)Cl2
-
Pd(L2)Cl2
109.5 (3)
110.1 (3)
Pd(L3)Cl2
109.5 (3)
Pd(L4)Cl2
111.74 (19)
107.27 (19)
94.69 (2)
90.95 (3)
86.66 (2)
87.69 (3)
2.2386 (7)
2.2433 (6)
2.3586 (7)
2.3435 (7)
C4-C2-C5 ()
C1-C2-C3 ()
P1-Pd1-P2
Cl1-Pd1-Cl2
P2-Pd1-Cl2
P1-Pd1-Cl1
P1-Pd1
117.0 (5)
90.58 (5)
90.78 (5)
91.10 (5)
87.74 (5)
2.249 (2)
2.244 (1)
2.351 (1)
2.358 (2)
108.2 (3)
95.84 (3)
91.59 (3)
84.49 (3)
88.09 (3)
2.2371 (9)
2.2423 (9)
2.3391 (9)
2.3570 (9)
96.29 (4)
91.85 (4)
shows
a
 angle compression. This bond angle
modification is due to a distortion in the 6-membered
chelate ring comprising of the C3 backbone, both P donor
atoms and the Pd metal center. The original chair
conformation adopted in the case of L1 and L2 distorts
towards a half-chair in L3, with the Pd metal atom
moving upwards toward planarity with the P donor
atoms, while maintaining the square planar geometry
expected of a Pd(II) d8 complex.
86.37 (4)
85.59 (4)
2.2452 (11)
2.2449 (11)
2.3480 (10)
2.3381 (12)
P2-Pd1
Pd1-Cl2
Pd1-Cl1
There is an increase in P-Pd-P ligand bite angle from
91° (L1) to 95-96° (L2-L4). It is clear from this study that
this parameter alone is not sufficient to describe the
ligand system. Due to distortions in the 6-membered
chelate ring, the relationship between gem-dialkyl group
size and ligand bite angle is complicated. The
perturbation of the P-Pd-P bite angle is accommodated
without altering the Cl-Pd-Cl bond angle, which remains
constant at 90-91° across the series. Instead, a distortion
a Values for [Pd(L1)Cl2] taken from literature.31
Comparison of  angles in the solid state structures of
[Pd(L)Cl2] across the series shows a decreasing trend
going from 117° (L1) to 107° (L4) (see Table 2). From L3 to
L4, the gem-dialkyl effect of concurrent  angle
expansion and  angle compression is clearly noticeable.
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of the square planar geometry of the Pd(II) complex Falivene and co-workers have introduced
a
more
1
2
3
4
5
6
7
8
occurs, which is shown in Figure 7 as a twisting of the
chlorides out of the P-Pd-P plane.
comprehensive computational tool to probe the
coordination sphere around a metal center, with a
parameter termed ligand buried volume (%V_Bur).32 The
percentage ligand buried volume is defined as the amount
of space occupied by the ligand of interest in a sphere of a
specified radius around a given coordination center,
which in our case, is the Pd metal atom. Comparison of
the calculated %V_Bur of the diphenyl ligand series
shows a trend of increasing steric congestion from L1
(38.9%), L2 (41.1%), L3 (41.8%) and finally L4 (42.2%) in a
sphere of radius 5 Å around the Pd center (see Figure 8).
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Computational DFT Study
All theoretical calculations were carried out with
Gaussian 16.33 In addition to the [Pd(L)Cl2] complexes of
the four synthesized bis(diphenylphosphino)propane
ligands R = H (L1), Me (L2), iPr/iPent (L3) and iPr (L4), the
diethyl (LEt) and di(tert.-butyl) (LtBu) ligands have been
calculated for comparison (see Figure 8). Final geometry
optimizations were carried out with hybrid functional
B3LYP34-35 in combination with triple-ζ DEF2TZVPP36-37
basis set for C, H, O and P atoms and the Stuttgart-
Dresden (SDD) effective core potential (ECP) with the
corresponding basis set for Pd. All calculations were
performed at 298.15 K and at 423.15 K with Grimme
dispersion correction38 and Becke-Johnson damping.39-40
Figure 7. Overlaid crystal structures of Pd(L1)Cl2 (orange)
and Pd(L2)Cl2 (red).
There are also subtle changes in the overall spatial
orientation of the ligand that influence the coordination
sphere around the metal center. Classical methods of
quantifying ligand steric bulk such as the Tolman cone
angle3 are not sufficient to probe these nuances since it
measures the substituents directly connected to the P
donor atom. The gem-dialkyl effect acts as an indirect
modification via the ligand backbone to influence the
overall structure of the complex without modifying the
substituents directly attached to the P donor atoms.

R
R

H
H
Ph2P P-Pd-P PPh2
Pd
R =
(Et)
(iPr/iPent) (iPr)
(tBu)
(Me)
(H)
Cl
Cl
%V_Bur
5
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Figure 8. Graphs of Pd(L)Cl2 parameters with error bars at 99.7% confidence. (i) Top Left:  angle vs. R group (ii) Top Right: 
angle vs. R group (iii) Bottom Left: P-Pd-P angle vs. R group (iv) Bottom Right: %V_Bur vs. R group.
The calculated α angle increases with increasing steric
bulk of the geminal R groups, from 109° in the dimethyl
ligand (L2) to 115° for the di-tert-butyl ligand. Conversely,
the β angles decrease from 115° for the plain ligand (L1,
where R = H) to 107° for the di-iso-propyl ligand (L4).
This simultaneous α angle expansion and β angle
compression follows what is expected of the gem-dialkyl
effect. Interestingly, the calculated β angle appears to
increase to 110° for the bulkiest di-tert-butyl ligand (LtBu).
Upon closer inspection of the structures, it appears that
the steric repulsion of the larger gem-dialkyl groups twists
the 6-membered chelate ring instead of solely
compressing the  bond angle. This results in a distortion
of the initial chair conformation seen for R = H, Me
towards a half-boat (R = Et, iPr/iPent) and ultimately to a
twist-boat conformation for R = iPr and tBu, as illustrated
in Figure 9. These calculations were performed at 298.15
K and calculations at elevated temperature (423.15 K) have
shown very similar distortions (see Figure S52).
Figure 9. [Pd(L)Cl2] structures calculated at room temperature and arranged by increasing steric bulk of gem-dialkyl
substituents showing 6-member chelate conformations (side view across P–C bonds). Phenyl groups and hydrogen atoms
removed for clarity.
The calculated P-Pd-P ligand bite angles follow
closely the experimentally determined angles based on
XRD data, reaching a maximum at 97° for R = Me and Et.
For these smaller R groups (R = Me, Et), the gem-dialkyl
effect alters the spatial environment by introducing steric
bulk to the C3-bridge that prompts a rearrangement of the
phosphorus substituents (see Figure 7) and widens the
is an accompanying distortion in the 6-membered chelate
ring that results in a decrease of the P-Pd-P ligand bite
angle. The accumulation of these three effects: (1) R-C-R
 bond angle increase, (2) C-C-C
 bond angle
compression and (3) twisting of the 6-membered chelate
ring, complicates the relationship between the gem-
dialkyl effect and P-Pd-P ligand bite angle, thereby
making it difficult to extract clear trends between them.
t
ligand bite angle. For larger R groups (R = iPr, Bu), there
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However, %V_Bur calculations indicate unambiguously
that there is a general trend toward greater restriction of
coordination space around the Pd metal center as R group
size increases.
1
2
3
4
5
6
7
Table 3. Pd-Catalyzed Hydroformylation of Octene.
O
H2
Hydroformylation
H
OH
CO/H2
+ branched isomers
+ branched isomers
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Isomerization
H2
H2
PPh2 PPh2
PPh2 PPh2
PPh2 PPh2
PPh2 PPh2
+ Z-isomers
L4
L2
L3
L1
Olefin Yield (Relative to
All Olefins) / %
#
1
Olefin
L
L/
Pd
Time Conv
/ h
1-
Oct
2-
Oct
3-
4-
Oct
Oct
Nonanal
Nonanolb Activi
Mole
Bal / %
/ %
Oct
ane (lin.)a / % (lin.)a / %
tyc
1-octene
L1
2.4
5
99
1
(2)
1
21
17
8
(17)
8
4
7
8
4
5
6
9
0
0
1
46 (73)
36 (72)
16 (67)
25 (84)
24 (84)
42 (72)
18 (70)
67 (70)
51 (70)
34 (67)
30 (67)
18 (71)
2 (90)
1 (91)
450
99
100
96
93
(44) (37)
26 20
(47) (36)
33 22
(50) (34)
2
3
1-octene
1-octene
1-octene
1-octene
1-octene
1-octene
1-octene
1-octene
1-octene
1-octene
L2 2.4
5
5
99
98
72
84
99
97
99
99
99
99
37
450
450
400
450
450
450
600
550
550
550
200
100
(2)
2
(15)
9
L3
L1
2.4
2.4
6 (91)
(3)
28
(44)
16
(26)
1
(13)
3
4d
5d
6
5
26
(40)
28
7
(11)
5
0 (n.a.)
0 (n.a.)
1 (91)
(5)
14
L2 2.4
5
92
99
100
97
94
95
(44)
23
(8)
18
(22)
9
L1
L3
L1
L2
L3
L4
L1
1.1
1.1
1.1
1.1
1.1
1.1
2.4
5
(2)
3
(46) (35)
38 23
(53) (32)
10 12
(17)
8
7
5
2 (94)
2 (88)
2 (89)
9 (91)
(4)
1
(11)
5
8
24
24
24
24
5
(2)
1
(37) (42) (19)
9
16
(40) (41)
21 20
17
7
(17)
9
(2)
1
10
11
(2)
1
(41) (40) (17)
22
(41)
63
22
(41)
10
8
(16)
4
0
4
4
0
0
9 (90)
<1 (n.d.)
<1 (n.d.)
1 (83)
92
100
97
94
90
(2)
1
12
13
14
15
trans-2-
octene
(1)
1
(81)
73
(13)
9
(5)
3
trans-2-
octene
L2 2.4
5
27
58
48
7 (69)
(1)
1
(85) (10)
(4)
42
trans-4-
octene
L1
1.1
1.1
24
24
11
12
27 (66)
14 (65)
300
250
(1)
1
(17)
11
(18) (64)
11 52
(15) (69)
trans-4-
octene
L2
1 (82)
(1)
(15)
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Thermodynamic Distribution of Octene
Isomers41
1
39
33
27
1
2
3
4
5
6
7
8
Conditions: Olefin, ligand, Pd(OAc)2 (0.17 mol%), CF3CO2H (Acid/Pd = 50), 60 bar CO/H2 (1:1), diglyme (0.9 M), 125 oC. Yields
were determined via gas chromatography using anisole as an internal standard. Statistical error analysis based on triplicate runs:
± 3%. n.d. = not determined. n.a. = not applicable. a Linearity = 1-isomer / sum of all regioisomers. b Derivatives of alcohol
products (i.e. esters/ethers) included. c Activity = moles of isomerization and carbonylation products / moles of catalyst. d
Acid/Pd = 5. Note: In all runs minor amounts (<1%) of by-products such as C17 ketones and diglyme-derived esters were detected.
percentage increase is limited considering the much
longer reaction time. Monitoring reactor pressures
showed that the rate of syngas uptake decreases over time
9
Pd-catalyzed Hydroformylation
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The bidentate bis(diphenylphosphine)propane ligands
as expected, and that most syngas uptake occurs during
L1-L4 were evaluated in Pd-catalyzed hydroformylation of
the first 5 hours (see Figure 10). Initial rates determined
1-octene and the results have been summarized in Table 3.
from these curves gave a relative order for the four
The catalyst was formed in-situ by mixing Pd(OAc)2 with
ligands L1-L4 of 2.5: 2.0: 1.6: 1.0.
ligand in diglyme followed by addition of CF3COOH (see
experimental section for details). The reaction conditions
were based on a previous study by Drent and Budzelaar.
42-43
Initial hydroformylation experiments of 1-octene were
carried out over 5 hours with a L/Pd ratio of 2.4 and 50
equiv. CF3COOH as a co-catalyst. The product spectrum
consists of octane, a mixture of linear octenes, a mixture
of linear and branched nonanal isomers, as well as some
linear and branched nonanol isomers. Comparing L1-L3,
while conversions are all high (>98%), a decrease in the
formation of nonanal and a greater proportion of internal
olefins was observed (runs 1-3). The increase in steric bulk
at the ligand backbone appears to reduce the rate of
hydroformylation. The ratio of linear versus branched
hydroformylation products is hardly affected by the
different ligands. The composition of the olefin mixture is
close to the expected thermodynamic composition in all
cases (1:39:33:27 for 1-, 2-, 3- and 4-octene at room
temperature).41 This indicates that the rate of
isomerization must be fast in all cases relative to the rate
of hydroformylation. In the case of L3, more
hydrogenation to nonanol is observed. The lower
hydroformylation activity for L3 suggests that reductive
hydroformylation from 1-octene to 1-nonanol can be
favored by increasing the gem-dialkyl effect. The alcohol
linearity is generally higher than aldehyde linearity,
indicating that the hydrogenation step favors primary
over secondary aldehyde substrates. A mechanism for the
homogeneously catalyzed reduction of aldehydes to
alcohols has been proposed by Zhou and co-workers.44
Figure 10. Pressure profile for hydroformylation runs 8-11.
After a reaction time of 24 hours, similar trends as
before are seen in going from L1-L4: increasing steric bulk
in the ligand backbone reduces nonanal formation, and
reductive hydroformylation to alcohols increases for the
bulkier ligands L3 and L4. Internal alkenes (trans-2-
octene and trans-4-octene) were also investigated as
substrates using L1 and L2. Both substrates can be
hydroformylated,
indicating
that
isomerizing
hydroformylation is indeed possible with these ligands,
albeit with lower conversion compared to 1-octene (runs
12-15). Hydroformylation of internal alkenes will be
inherently slower than terminal alkenes, as the linear
aldehyde remains the major product irrespective of the
octene isomer that is used as the substrate. Isomerization
from the internal octenes to 1-octene will need to occur
prior to hydroformylation,45-46 which seems to be equally
fast for both ligands according to the olefin composition.
The subsequent hydroformylation of 1-octene is faster for
L1 than for L2, as seen in runs 1-2.
Lowering the amount of acid to 5 equiv. CF3COOH
results in lower conversions and less isomerization to
internal olefins (runs 4-5). Isolation of the spent catalyst
after the hydroformylation reaction revealed the
formation of a bis(ligand) complex [Pd(L1)2](CF3COO)2
(see Supporting Information). The formation of
bis(ligand) complexes could be a potential catalyst
deactivation pathway. However, lowering the L/Pd ratio
to 1.1 gave very similar performance for ligands L1 and L3
(cf. run 6 vs. 1 and run 7 vs. 3), and subsequent runs were
therefore carried out using this lower ratio. Extending the
reaction time from 5 to 24 hours results in increased
hydroformylation yields (runs 8-11), though the
The mechanism for the palladium-catalysed
hydroformylation reaction has been little studied, in
contrast to rhodium-catalysed hydroformylation.19,20
Based on the currently available information, the
formation of [Pd(L)(CO)H]+ under the reaction
conditions (p(CO/H2) = 60 bar) is assumed as the starting
point in the catalytic cycle, formed from [Pd(L)X2]
through heterolytic activation of H2 and CO
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substituents, to affect catalyst performance. Further
coordination.47,48 An associative substitution with the
alkene substrate will give [Pd(L)(alkene)H]+, which
undergoes further insertion to a palladium alkyl complex.
studies into this intriguing effect with other ligands
applied in different catalytic processes are currently
underway.
1
2
3
4
Preliminary
DFT
calculations
(see
Supporting
Information) of these initial steps in the catalytic
hydroformylation cycle for the complexes with ligands L1,
L2 and the ditert.-butyl ligand LtBu have shown that the
gem-dialkyl effect does not affect the overall energy
barriers for alkene coordination and insertion (+25.3,
+25.7 and +24.7 kcal/mol for L1, L2 and LtBu respectively.
This is in agreement with the fast alkene isomerization
seen with all catalysts. The resting state is most likely a
palladium(II) acyl complex [Pd(L)(acyl)(CO)]+, as seen in
other palladium catalyzed carbonylation reactions
AUTHOR INFORMATION
5
6
7
8
Corresponding Author
*Email: g.britovsek@imperial.ac.uk
Notes
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The authors declare no competing financial interest.
Supporting Information
(alternating
CO-olefin
copolymerization,
olefin
methoxycarbonylation, etc.) and the final hydrogenolysis
step is presumed to be rate-determining in this case,
similar to methanolysis and hydrolysis reactions in
methoxy- and hydroxycarbonylation.49-50 Further studies
Experimental details, NMR spectra, computational
details, crystallographic details.
regarding
the
mechanism
of
Pd-cataylsed
ACKNOWLEDGMENTS
hydroformylation and the effect of gem-dialkyl
substituents on the selectivity are ongoing.
We gratefully acknowledge the Agency for Science,
Technology & Research (A*STAR) for the funding of this
research. We would like to thank Angeline Seo for mass
spectrometry and elemental analysis.
3. CONCLUSION
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