Synthesis and application of tetraphosphane ligands in rhodium-catalyzed hydroformylation of terminal olefins: High regioselectivity at high temperature

Article abstract of DOI:10.1002/chem.200903109

A new class of substituted tetraphosphane ligands has been developed and applied in the rhodium-catalyzed regioselective hydroformylation of terminal olefins. The high regioselectivity (linear selectivity is above 97% for 1-octene and 1-hexene) at high temperature (140°C) shown by these tetraphosphane ligands is remarkable considering the low regioselectivity commonly observed under similar reaction conditions when other bisphosphane analogues are used. The steric and electronic effects of substituents on the diarylphosphane moiety have also been examined.

Full text of DOI:10.1002/chem.200903109

DOI: 10.1002/chem.200903109
Synthesis and Application of Tetraphosphane Ligands in Rhodium-Catalyzed
Hydroformylation of Terminal Olefins: High Regioselectivity at High
Temperature
Shichao Yu,[a] Xiaowei Zhang,[a] Yongjun Yan,[a] Chaoxian Cai,[a] Liyan Dai,*[a, b] and
Xumu Zhang*[a]
Abstract: A new class of substituted
tetraphosphane ligands has been devel-
oped and applied in the rhodium-cata-
lyzed regioselective hydroformylation
of terminal olefins. The high regioselec-
tivity (linear selectivity is above 97%
for 1-octene and 1-hexene) at high
temperature (1408C) shown by these
tetraphosphane ligands is remarkable
considering the low regioselectivity
commonly observed under similar reac-
tion conditions when other bisphos-
phane analogues are used. The steric
and electronic effects of substituents
on the diarylphosphane moiety have
also been examined.
Keywords: biaryls · hydroformyla-
tion · phosphane ligands · regiose-
lectivity · rhodium
Introduction
Xantphos,[3] Biphephos,[4] Naphos,[5] calix[4]arene bisphos-
phite,[6] pyrrole-based bisphosphoramidite,[7] and self-assem-
bled bisphosphane.[8] Hydroformylation with these catalytic
systems are generally carried out at a relatively low temper-
ature (below 1258C) to ensure high regioselectivity. Since
hydroformylation reactions at high temperatures afford
higher reaction rates, from the view of industrial applica-
tions, it is desirable to develop regioselective ligands for
high-temperature hydroformylation. Another challenge that
is important to industry is the hydroformylation of long-
chained olefins; in these cases, the produced aldehydes have
high boiling points and thus require high-temperature distil-
lation during the production process, which means that the
ligands used in the reaction must be tolerant towards high
temperatures. Herein, we would
Hydroformylation of olefins represents one of the most im-
portant reactions in industry. The reaction is catalyzed by
homogeneous catalysts and leads to products containing an
aldehyde group that are versatile intermediates and building
blocks for various pharmaceuticals, agrochemicals, commod-
ity and fine chemicals.[1] Production volumes obtained by
using this process are estimated to be over nine million tons
annually. Most commercial hydroformylation processes use
highly reactive rhodium catalysts that are modified with
either mono- or bisphosphorus ligands to address the issue
of regio- and stereoselectivity. Phosphane- and phosphite-
based systems giving highly regioselective linear aldehydes
have been reported. Some elegant examples include Bisbi,[2]
like to report the design and
synthesis of a new class of tetra-
phosphane ligands 1 that are
[a] Dr. S. Yu, X. Zhang, Dr. Y. Yan, C. Cai, Prof. L. Dai, Prof. X. Zhang
Department of Chemistry and Chemical Biology
& Pharmaceutical Chemistry, Rutgers
The State University of New Jersey
based on a biphenyl backbone,
and describe their application
in the highly regioselective hy-
droformylation of terminal ole-
Piscataway, New Jersey 08854 (USA)
Fax : (+1)732-445-6312
fins.[9]
E-mail: xumu@rci.rutgers.edu
One of the reasons for the reduced regioselectivity of Rh-
catalyzed hydroformylation reactions at high temperature is
the formation of unselective catalytic species due to the dis-
sociation of phosphorus ligands from the metal center. Car-
bonyl monoxide is a strong p acid that competes to bind to
the rhodium center with the phosphorus ligand; at high tem-
[b] Prof. L. Dai
College of Materials Science and Chemical Engineering
Zhejiang University, Hangzhou 310027
Zhejiang (P.R. China)
Fax : (+86)571-8795-2693
E-mail: dailiyan@zju.edu.cn
4938
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Chem. Eur. J. 2010, 16, 4938 – 4943

FULL PAPER
perature the exchange between the ligands is also accelerat-
ed. To ensure the formation of the selective catalytic species,
usually a large excess of monophosphorus ligands are used.
The development of bisphosphorus ligands affords higher
regioselectivity and requires lower amounts of ligand, which
may partly arise from the formation of more selective,
bulky, and robust catalytic species (Scheme 1). Thus, we en-
property of the N-pyrrolylphosphorus moiety.[7] Ligand 1
has similar coordination modes to those of the tetraphos-
phoramidite, but with more electron-rich phosphorus moiet-
ies. The latter character may reduce the extent of double-
bond isomerization during the hydroformylation process as
observed for electron-donating bisphosphanes such as
Bisbi.[2] Thus, we envisioned that ligand 1 could be a good
candidate for the regioselective hydrofor
nal olefins with low isomerization.
ACHUTGTNRENNmGU ylACHTUGNTRENaNUGN tion of termi-
Results and Discussion
The synthesis of ligand 1 was realized as shown in Scheme 3.
Starting from the ozonolysis of pyrene (2), reduction of bi-
phenyl-2,2’,6,6’-tetracarbaldehyde (3) by sodium borohy-
Scheme 1. Ligand dissociation in hydroformylation.
visaged that tetraphosphane ligand 1 should afford better re-
gioselectivity at high temperatures than its bisphosphane an-
alogue Bisbi for the following reasons: 1) Ligand 1 has a
higher concentration of the selective catalytic species due to
the presence of multiple chelating modes: a rhodium metal
center can form four possible equivalent bidentate com-
plexes. 2) When ligand 1 coordinates to the metal to form a
bidentate system, the nearby intramolecular free phosphorus
atoms can effectively increase the local phosphorus concen-
tration around the metal center and enhance the chelating
ability. When a phosphane moiety in the bidentate ligand
dissociates from the metal, two intermediates are formed by
recoordination of another two phosphane moieties to the
Rh center to reform the bidentate system (Scheme 2). Such
“enhanced multidentarity” has been demonstrated to en-
hanced the ligandsꢁ ability to stabilize catalytic systems and
promote their longevity in transition-metal-catalyzed cou-
pling reactions.[10]
Scheme 3. The synthesis of tetraphosphane ligand 1.
This multidentarity effect has also been observed in our
previously developed pyrrole-based tetraphosphoramidite li-
gands for the regioselective hydroformylation of internal
olefins, styrene and its derivatives, vinyl acetates, and dienes,
which all show exceptionally high regioselectivity towards
the formation of linear aldehydes.[11] The peculiar behavior
of those ligands was ascribed to the large bite angle formed
by coordination with the metal (nine-membered ring), the
multiple coordination modes increase the concentration of
the selective catalytic species, and the electron-withdrawing
dride, and bromination of 2,2’,6,6’-tetrakis(hydroxymethyl)-
biphenyl (4), tetrabromide 5 was prepared in high yields.[12]
Whereas the synthesis of Bisbi by reaction of lithium di-
ACHUTNGERNpNUG henAHCTUNGTRNENyUGN lphosphane with 2,2’-bisbromomethyl-1,1’-biphenyl
was reported to occur in high yield,[2a] the reaction of tetra-
bromide 5 with lithium diphenylphosphane gave a complex
mixture of unidentified products as monitored by 31P NMR
spectroscopy in situ. The reactivity of tetrabromide 5 was
thus very different from its cor-
responding dibromide, 2,2’-bis-
bromomethyl-1,1’-biphenyl. To
overcome this problem, we con-
verted tetrabromide 5 into the
less reactive tetrachloride 6 by
the reaction of the tetrabro-
mide with lithium chloride in
DMF at room temperature; the
Scheme 2. Enhanced chelating ability of 1 through multiple chelating modes and increased local phosphorus
concentration.
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4939

X. Zhang, L. Dai et al.
tetrachloride 6 was obtained in high yield (93%). We were
pleased to find that the reaction of tetrachloride 6 with lithi-
um diarylphosphane[13] cleanly afforded the desired tetra-
phosphane as indicated by a single peak in 31P NMR spectra,
which was recorded in situ. Since tetraphosphane 1 is an air-
sensitive compound, tetraphosphane 1 was protected in situ
with borane for purification. A simple deprotection of the
ing that low CO/H2 pressures facilitate the olefin isomeriza-
tion.
For comparison, bisphosphane ligand Bisbi was prepared
and employed in the hydroformylation of terminal olefins
under the same reaction conditions. The results, summarized
in Table 2, clearly show that, in all cases, the use of tetra-
borane with 1,4-diazabicycloACTHNUTRGENUGN[2.2.2]octane (DABCO) afford-
Table 2. Comparison of tetraphosphane and bisphosphane ligands.[a]
ed the desired tetraphosphane ligand 1 in 64–79% yield.
Hydroformylation of terminal olefins with the new ligand
1a was then investigated. The hydroformylation reaction
was conducted in toluene with 1-octene as the standard sub-
strate and decane as internal standard. The rhodium catalyst
was prepared in situ by mixing the ligand 1a with [Rh-
Substrate T
[8C]
Ligand n/i[b] Linear Isomerization TON[e] TOF[f]
[%][c] [%][d] [hÀ1
N
]
1
2
3
4
5
6
7
8
9
1-octene 140 1a
1-octene 140 Bisbi
1-octene 120 1a
1-octene 120 Bisbi 29.5 96.7
1-octene 100 1a 50.5 98.1
1-octene 100 Bisbi 45.2 97.8
1-hexene 140 1a
1-hexene 140 Bisbi
1-hexene 120 1a
45.2 97.8 6.5
24
1.8ꢂ103 9.3ꢂ103
1.5ꢂ103 6.2ꢂ103
1.8ꢂ103 7.3ꢂ103
1.8ꢂ103 5.7ꢂ103
1.8ꢂ103 2.5ꢂ103
1.6ꢂ103 3.4ꢂ103
1.8ꢂ103 9.5ꢂ103
1.6ꢂ103 8.7ꢂ103
1.8ꢂ103 6.6ꢂ103
1.8ꢂ103 6.0ꢂ103
1.8ꢂ103 3.3ꢂ103
1.7ꢂ103 2.6ꢂ103
2.4 70.6
ACHTUNGTRENNUNG(acac)(CO)2] (acac=acetylacetonate) in toluene. The sub-
49.8 98.0
5.8
8.7
5.6
6.7
7.7
strate/catalyst ratio was 2000 and the catalyst concentration
was 1.0 mm. The reaction was terminated after one hour.
The effects of the ligand/metal ratio on hydroformylation
of terminal olefins with the tetraphosphane ligand 1a were
examined. As shown in Table 1 (entries 1–4), a slight de-
crease in both the linear/branched (n/i) ratio and isomeriza-
tion were observed when the ligand/metal ratio was in-
creased from 1:1 to 6:1. The effects of reaction temperature
on the hydroformylation reaction were also investigated
(Table 1, entries 3, and 5–7). To our delight, only a slight de-
crease in the n/i ratio was observed when the reaction tem-
perature was increased from 100 to 1408C. As expected, hy-
droformylation at lower temperatures led to less olefin
43.8 97.8
4.9 83.1
48.5 98.0
20
7.1
9.1
6.6
9.4
10 1-hexene 120 Bisbi 35.8 97.3
11 1-hexene 100 1a 48.6 98.0
12 1-hexene 100 Bisbi 43.2 97.7
[a] Reagents and conditions: substrate/catalyst ratio=2000, [Rh]
(1.0 mm), ligand/Rh ratio=4:1, CO/H2 (10/10 atm), 1 h, toluene, decane
as internal standard. [b] Linear/branched ratio determined by GC analy-
sis. [c] Percentage of linear aldehyde in all aldehydes. [d] Isomerization
of internal olefin. [e] Turnover number, determined by GC analysis.
[f] Turnover frequency, determined by GC analysis, reaction time=
10 min.
isomACHTUNGTRENNUNGerization. Finally, the effects of CO/H2 pressure were
tested (Table 1, entries 3, 8–10). At high CO/H2 pressure,
the regioselectivities were low, however, the regioselectivi-
ties could be increased by lowering the CO/H2 pressure. The
highest regioselectivity (n/i ratio 66.7) was obtained under a
CO/H2 pressure of 5/5 atm. However, a significant amount
of isomerization was observed under this pressure, indicat-
phosphane ligand 1a afforded higher regioselectivity than
Bisbi under the same reaction conditions. It should be noted
that, at high temperature, a dramatic decrease in the regio-
selectivity and a high percentage of isomerization was ob-
served with bisphosphane ligand Bisbi (Table 2, entries 1, 2,
and 8). For example, in the hydroformylation of 1-octene,
the regioselectivity was much lower (n/i=2.4) and the
extent of isomerization was significant (24%) at 1408C with
Bisbi as ligand (Table 2, entry 2); whereas, the regioselectivi-
ty remained high (n/i=45.2) and the isomerization remained
low (6.5%) using tetraphosphane ligand 1a at the same
temperature (Table 2, entry 1). At lower temperature
(1008C), both tetraphosphane 1a and bisphosphane Bisbi af-
forded high regioselectivity and low isomerization, with n/i
ratios greater than 40 and isomerization less than 10%
(Table 2, entries 5, 6, 11, and 12). The similar performances
with both ligands at low temperature and dramatic differen-
ces observed at high temperature suggest that the superior
performance of ligand 1a at high temperature is indeed due
to the enhanced chelating ability of ligands 1. This result is
also important from the practical point of view because
highly regioselective hydroformylation can, under these con-
ditions, now be carried out at higher temperature, with sub-
sequently higher reaction rates.
Table 1. Optimization of reaction conditions for the hydroformylation of
1-octene with Rh/ligand (L) 1a.[a]
L/Rh
T
[8C]
CO/H2 n/i[b] Linear Isomerization TON[e]
[atm]
[%][c]
[%][d]
1
2
3
4
5
6
7
8
9
1:1
2:1
4:1
6:1
4:1
4:1
4:1
4:1
4:1
100
100
100
100
140
120
80
100
100
100
10/10
10/10
10/10
10/10
10/10
10/10
10/10
30/30
20/20
5/5
53.7
53.4
50.5
48.9
45.2
49.8
34.2
16.5
22.3
66.7
98.2
98.2
98.1
98.0
97.8
98.0
97.2
94.3
95.7
98.5
7.9
7.3
5.6
5.6
6.5
5.8
3.4
2.9
3.0
17.3
1.8ꢂ103
1.8ꢂ103
1.8ꢂ103
1.8ꢂ103
1.8ꢂ103
1.8ꢂ103
1.4ꢂ103
1.2ꢂ103
1.2ꢂ103
1.6ꢂ103
10 4:1
[a] Reagents and conditions: substrate/catalyst ratio=2000, [Rh]
(1.0 mm), toluene, 1 h, decane as internal standard. [b] Linear/branched
ratio determined by GC analysis. [c] Percentage of linear aldehyde in all
aldehydes. [d] Isomerization of internal olefin. [e] Turnover number, de-
termined by GC analysis.
Ligands 1b–f were then applied to rhodium-catalyzed hy-
droformylation of terminal olefins 1-hexene and 1-octene
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Chem. Eur. J. 2010, 16, 4938 – 4943

Tetraphosphane Ligands in Hydroformylation
FULL PAPER
Table 4. Hydroformylation of 1-octene by using tetraphosphane ligands
under a range of reaction temperatures (Tables 3 and 4). It
was found that the introduction of substituents at the di-
1b–f at a range of temperatures.[a]
ACHTUNGTRENNUNGphenACHTUNGTRENNUNGylphosphane moiety of 1a affected both the regioselec-
L
T
[8C]
n/i[b]
Linear
[%][c]
Isomerization
[%][d]
TON[e]
TOF
Table 3. Hydroformylation of 1-hexene by using tetraphosphane ligands
[f]
ACHTUNGTRENNUNG ]
[hÀ1
1b–f at a range of temperatures.[a]
1
2
3
4
5
6
7
8
1b
1b
1b
1c
1c
1c
1d
1d
1e
1e
1 f
1 f
140
120
100
140
120
100
140
120
140
120
140
120
47.4
53.7
77.9
17.9
33.5
63.2
24.4
38.9
42.8
67.3
52.4
64.1
97.9
98.2
98.7
94.7
97.1
98.4
96.0
97.5
97.7
98.5
98.1
98.4
5.7
5.4
4.9
7.1
6.8
5.2
7.7
7.4
5.4
4.5
5.6
5.1
1.9ꢂ103
1.9ꢂ103
1.8ꢂ103
1.9ꢂ103
1.9ꢂ103
1.9ꢂ103
1.6ꢂ103
1.2ꢂ103
1.9ꢂ103
1.9ꢂ103
1.9ꢂ103
1.8ꢂ103
1.0ꢂ104
9.1ꢂ103
7.4ꢂ103
9.7ꢂ103
7.9ꢂ103
5.3ꢂ103
6.3ꢂ103
5.5ꢂ103
1.2ꢂ104
9.1ꢂ103
1.4ꢂ104
1.1ꢂ104
L
T
[8C]
n/i[b]
Linear Isomerization TON[e]
TOF[f]
[hÀ1
[%][c]
[%][d]
N
]
1
2
3
4
5
6
7
8
9
1b 140
1b 120
1b 100
87.9 98.9
4.8
4.6
4.2
5.1
4.8
4.5
7.4
7.2
8.7
6.5
8.8
6.6
1.8ꢂ103 1.1ꢂ104
1.8ꢂ103 7.6ꢂ103
1.8ꢂ103 5.7ꢂ103
1.8ꢂ103 9.9ꢂ103
1.8ꢂ103 7.3ꢂ103
1.8ꢂ103 5.1ꢂ103
1.4ꢂ103 6.1ꢂ103
1.1ꢂ103 5.3ꢂ103
1.8ꢂ103 1.1ꢂ104
1.8ꢂ103 9.9ꢂ103
1.8ꢂ103 1.6ꢂ104
1.8ꢂ103 1.3ꢂ104
92.1 98.9
125.9 99.2
64.1 98.5
87.3 98.9
95.7 98.9
41.3 97.6
44.8 97.8
32.4 97.0
55.2 98.2
28.8 96.6
49.3 98.0
9
1c
1c
1c
140
120
100
10
11
12
1d 140
1d 120
[a] Reagents and conditions: substrate/catalyst ratio=2000, [Rh]
(1.0 mm), toluene, 1 h, decane as internal standard. [b] Linear/branched
ratio determined by GC analysis. [c] Percentage of linear aldehyde in all
aldehydes. [d] Isomerization of internal olefin. [e] Turnover number, de-
termined by GC analysis.
1e
140
120
140
120
10 1e
11 1 f
12 1 f
[a] Reagents and conditions: substrate/catalyst ratio=2000, [Rh]
(1.0 mm), toluene, 1 h, decane as internal standard. [b] Linear/branched
ratio determined by GC analysis. [c] Percentage of linear aldehyde in all
aldehydes. [d] Isomerization of internal olefin. [e] Turnover number, de-
termined by GC analysis.
Conclusion
A series of substituted tetraphosphane ligands 1, have been
designed, synthesized, and applied in the rhodium-catalyzed
hydroformylation of terminal olefins. Compared with the
low regioselectivity at high temperature commonly observed
when other bisphosphane analogues are used, the high per-
formance achieved by the tetraphosphane ligands 1 is re-
markable. The steric and electronic effects of substituents
on the diarylphosphane moiety were also examined. Further
applications of the ligands and studies on the mechanism
are under investigation and will be reported in due course.
tivity of the aldehydes and the activity of the catalytic
system. In both cases, the catalytic system with ligands 1b,
1c, 1e, and 1 f, which contain electron-withdrawing substitu-
ents, showed higher activity than with ligand 1d, which con-
tains an electron-donating group. The trend for those ligands
on the regioselectivity, however, was not as clear. Whereas
ligand 1b afforded the best linear to branch ratio at 1408C
for 1-hexene (87.9), ligand 1 f was found to be somewhat
better than 1b for 1-octene under similar reaction condi-
tions (52.4 versus 47.4) (see Table 3, entry 1, and Table 4, en-
tries 1 and 11). The position of the substituents may also
exert some influence on the regioselectivity. Ligand 1c, con-
taining a trifluoromethyl substituent at the para-position of
Experimental Section
General: All reactions and manipulations were performed either in a ni-
trogen-filled glove box or by using standard Schlenk techniques, unless
otherwise noted. Solvents were dried according to standard procedures
and degassed with N2. Column chromatography was performed with 200–
400 mesh silica gel supplied by Natland International Corporation. 1H,
13C, 19F, and 31P NMR spectra were recorded with either a Bruker ad-
vance 400 MHz NMR spectrometer or a Varian VNMRS 300 MHz spec-
trometer. GC analyses were conducted with a Helwett–Packard 6890 gas
chromatograph fitted with capillary columns.
the diACHTUNGTRENNUNGphenACHTUNGTRENNUNGylphosphane moiety, gave a higher linear to
branch ratio for the hydroformylation of the 1-hexene than
the corresponding ligand 1e with the same substituent at the
meta-position (see Table 3, entries 4 and 9). Apparently,
ligand 1e has a larger steric effect than ligand 1c. This
effect was reversed when 1-octene was examined (see
Table 4, entries 4 and 9). With one more trifluoromethyl
substituent at the meta-position of the diphenylphosphane
moiety, the increase in the regioselectivity observed for the
reaction with 1-octene was continued, whereas that with
1-hexene decreased (see Table 3, entry 11 and Table 4,
entry 11). From these results, it can clearly be seen that
subtle changes in the substrate chain length can require a
change in the choice of suitable ligand.
Synthesis of 4: LiCl (2.82 g, 67.2 mmol) was added to a solution of 3
(2.2 g, 4.2 mmol) in DMF (80 mL). The reaction mixture was stirred at
RT for 6 h then cooled to 08C and an aqueous solution of HCl (5%,
30 mL) was added carefully. After stirring for 5 min, the mixture was ex-
tracted with diethyl ether (4ꢂ40 mL) and washed with a saturated aque-
ous solution of NaCl (80 mL). The organic layer was separated, dried
over Na2SO4, and concentrated to dryness. Pure product was obtained as
a white solid by recrystallization from CH2Cl2/hexanes (1.35 g, 93%
1
yield). H NMR (300 MHz, CD2Cl2): d=7.74–7.62 (m, 4H), 7.59–7.56 (m,
2H), 4.28 ppm (s, 8H); 13C NMR (75 MHz, CD2Cl2): d=137.0, 135.8,
131.2, 130.2, 45.0 ppm; HRMS (EI+): m/z: calcd for C16H14Cl4: 345.9853
[M]+; found: 345.9850.
Chem. Eur. J. 2010, 16, 4938 – 4943
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4941

X. Zhang, L. Dai et al.
Synthesis of 5a: Typical procedure: nBuLi (5.28 mL, 2.5m in hexane,
13.2 mmol) was added dropwise to a cooled (À788C) solution of diphen-
ylphosphane (2.32 mL, 13.2 mmol) in THF (10 mL). After stirring for
10 min, the reaction mixture was allowed to warm to RT and stirred for
30 min. The reaction mixture was cooled to À788C and (1.05 g,
1.6 g, 4.6 mmol), and BH3 (1.0m in THF, 200 mL, 200 mmol). Yield: 4.9 g
(68.9%); white solid; H NMR (400 MHz, CDCl3): d=7.84 (t, J=6.4 Hz,
1
G
ACHTUNGTRENNUNG
16H), 7.66 (d, J=6.4 Hz, 16H), 6.99 (t, J=7.6 Hz, 2H), 6.63 (d, J=
7.6 Hz, 4H), 3.52 (d, J=13.6 Hz, 8H), 1.40–0.60 ppm (brs, 12H);
13C NMR (100 MHz, CDCl3): d=138.6 (t, J=7.7 Hz), 134.3 (d, J=
52.3 Hz), 133.3 (qd, 1J=33.6, 2J=2.3 Hz), 132.5 (d, J=9.5 Hz), 129.7 (d,
J=1.5 Hz), 128.5, 126.0 (dd, 1J=9.8, 2J=3.8 Hz), 123.3 (q, J=270.1 Hz),
29.6 ppm (d, J=33.7 Hz); 19F NMR (376 MHz, CDCl3): d=À63.4 ppm;
31P NMR (161 MHz, CDCl3): d=16.2 ppm; HRMS (ESI): m/z: calcd for
C72H58B4F24P4: 1546.3478 [M]+; found: 1546.3466.
4
3 mmol) in THF (10 mL) was added dropwise. After addition, the reac-
tion mixture was allowed to warm to RT slowly and stirred overnight.
The reaction mixture was cooled to 08C and a cold solution of BH3
(1.0m in THF, 132 mL, 132 mmol) was added dropwise. The mixture was
allowed to warm to RT and stirring was continued for 4 h. The reaction
mixture was cooled to 08C and water (20 mL) was added carefully to
quench the excess BH3. Volatile material was removed under vacuum
and CH2Cl2 (50 mL) and water (50 mL) were added to the residue. The
mixture was stirred for 10 min until all of the residue dissolved. The or-
ganic phase was separated and the aqueous phase was extracted with
CH2Cl2 (2ꢂ25 mL). The combined organic phase was washed with a satu-
rated aqueous solution of NaCl (50 mL) and dried with Na2SO4. The sol-
vent was removed under reduced pressure to obtain an off-white solid.
EtOAc (10 mL) was added to the crude solid and the resulting suspen-
sion was stirred for 30 min and filtered. The residue was washed with
cold EtOAc (2ꢂ5 mL) to give the pure borane-protected title compound
5a as a colorless solid (2.5 g, 73.8%). 1H NMR (300 MHz, CDCl2): d=
7.58–7.52 (m, 16H), 7.45–7.39 (m, 8H), 7.36–7.31 (m, 16H), 7.03–6.97 (m,
2H), 6.87–6.84 (m, 4H), 3.16 (d, J=13.4 Hz, 8H), 1.53–0.75 ppm (brs,
12H); 13C NMR (75 MHz, CD2Cl2): d=133.1, 132.5 (d, J=9.1 Hz), 131.5,
131.3, 130.6, 130.4, 129.2 (d, J=9.9 Hz), 127.5, 30.2 ppm (d, J=30 Hz);
31P NMR (146 Hz, CD2Cl2): d=15.2 ppm; HRMS (ES+): m/z: calcd for
C64H66NaP4B4: 1025.4385 [M+Na+]; found: 1025.4431.
Compound 1c: Prepared according to the typical procedure by using
complex 5c (773 mg, 0.5 mmol) and DABCO (0.448 g, 4.0 mmol). Yield:
559 mg (75.0%); white solid; 1H NMR (400 MHz, CDCl3): d=7.42 (d,
J=7.6 Hz, 16H), 7.21 (t, J=18.2 Hz, 16H), 6.97 (t, J=7.6 Hz, 2H), 6.70
(d, J=7.6 Hz, 4H), 3.20 ppm (s, 8H); 13C NMR (100 MHz, CDCl3): d=
142.7 (t, J=26.4 Hz), 138.6, 136.2 (d, J=10.8 Hz), 133.2 (d, J=30.0 Hz),
131.4 (q, J=33.5 Hz), 128.7 (d, J=4.5 Hz), 128.2, 125.4 (t, J=3.1 Hz),
123.8 (q, J=270.2 Hz), 34.9 ppm (dd, 1J=10.2, 2J=5.4 Hz); 19F NMR
(376 MHz, CDCl3): d=À62.9 ppm; 31P NMR (146 MHz, CDCl3): d=
À14.1 ppm; HRMS (ESI): m/z: calcd for C72H47F24P4: 1491.2245
AHCTUNGTRENNUNG
[M+H+]; found: 1491.2237.
Complex 5d: Prepared according to the typical procedure by using di-
AHCTUNGERTG(NNUN 4-methylphenyl)phosphane (9.1 g, 42.8 mmol), nBuLi (2.5m in hexane,
17.2 mL, 42.8 mmol), 2,2’,6,6’-tetrakis(chloromethyl)biphenyl (3.4 g,
9.7 mmol), and BH3 (1.0m in THF, 200 mL, 200 mmol) in THF (250 mL).
Yield: 7.6 g (71.2%); white solid; 1H NMR (400 MHz, CDCl3): d=7.48
(t, J=9.2 Hz, 16H), 7.13–7.08 (m, 16H), 6.97 (t, J=7.8 Hz, 2H), 6.85 (d,
J=7.8 Hz, 4H), 3.17 (d, J=13.6 Hz, 8H), 2.35 (s, 24H), 1.15–0.85 ppm
(brs, 12H); 13C NMR (100 MHz, CDCl3): d=141.1 (d, J=2.2 Hz), 138.8
(d, J=7.7 Hz), 132.9, 132.0 (d, J=9.4 Hz), 129.7 (d, J=5.0 Hz), 127.9,
127.4, 127.1, 29.9 (d, J=35 Hz), 21.3 ppm; 31P NMR (161 MHz, CDCl3):
d=13.3 ppm; HRMS (ESI): m/z: calcd for C72H82B4P4: 1114.5722 [M]+;
found: 1114.5739.
Synthesis of ligand 1a: Typical procedure: Compound 5a (501 mg,
0.5 mmol) was added in portions to a solution of DABCO (448 mg,
4 mmol) in toluene (10 mL). The resulting suspension was stirred for
30 min at RT then slowly heated to 608C. Stirring was continued for 6 h
at 608C then the reaction mixture was cooled to RT and additional tolu-
ene (10 mL) was added. The diluted solution was charged on a short
silica gel column by cannula and eluted with toluene (40 mL). The sol-
vent was removed under vacuum to give the desired ligand 1a as a white
solid (376 mg, 79.4%). 1H NMR (300 MHz, CDCl2): d=7.32–7.22 (m,
40H), 6.91–6.86 (m, 2H), 6.76–6.74 (m, 4H), 3.24 ppm (s, 8H); 13C NMR
(75 MHz, CD2Cl2): d=139.6, 139.3, 137.1, 137.0, 133.5, 133.3, 128.9, 128.7,
Compound 1d: Prepared according to the typical procedure by using
complex 5d (1.10 g, 1.0 mmol) and DABCO (0.896 g, 8.0 mmol). Yield:
1
825 mg (78.0%); white solid; H NMR (400 MHz, CDCl3): d=7.16 (t, J=
7.2 Hz, 16H), 7.04 (d, J=7.2 Hz, 16H), 6.90 (t, J=7.6 Hz, 2H), 6.78 (d,
J=7.6 Hz, 4H), 3.16 (s, 8H), 2.33 ppm (s, 24H); 13C NMR (100 MHz,
CDCl3): d=138.1, 136.8 (d, J=11.4 Hz), 135.9 (d, J=14.5 Hz), 133.0 (d,
J=20.1 Hz), 129.4 (d, J=10.1 Hz), 129.0 (d, J=6.8 Hz), 128.0 (d, J=
5.1 Hz), 126.9, 34.7 (d, J=14.1 Hz), 21.3 ppm; 31P NMR (146 MHz,
CDCl3): d=À16.4 ppm; HRMS (ESI): m/z: calcd for C72H71P4: 1059.4501
[M+H+]; found: 1059.4522.
31
127.4, 35.0 ppm (d, J=25.8 Hz); P NMR (146 Hz, CD2Cl2): d=À15.3;
HRMS (ES+): m/z: calcd for C64H55P4: 947.3254 [M+H]+; found:
947.3237.
Complex 5b: Prepared according to the typical procedure by using
di(3,5-difluorophenyl)phosphane (7.9 g, 30.6 mmol), nBuLi (2.5m in
hexane, 12.3 mL, 30.6 mmol), 2,2’,6,6’-tetrakis(chloromethyl)biphenyl
(2.4 g, 6.9 mmol), and BH3 (1.0m in THF, 300 mL, 300 mmol). Yield:
Complex 5e: Prepared according to the typical procedure by using di-
(m-trifluoromethylphenyl)phosphane (8.3 g, 25.7 mmol), nBuLi (2.5m in
hexane, 10.3 mL, 25.7 mmol), 2,2’,6,6’-tetrakis(chloromethyl)biphenyl
(2.0 g, 5.8 mmol), and BH3 (250 mL, 1.0m in THF, 250 mmol). Yield:
6.0 g (67.1%); white solid; 1H NMR (400 MHz, CD2Cl2): d=7.98 (d, J=
10.8 Hz, 8H), 7.88 (t, J=8.8 Hz, 8H), 7.75 (t, J=8.8 Hz, 8H), 7.57 (td,
1J=7.6 Hz, 2J=2.0 Hz, 8H), 6.96 (t, J=8.0 Hz, 2H), 6.62 (d, J=8.0 Hz,
4H), 3.47 (d, J=13.2 Hz, 8H), 1.51–0.60 ppm (brs, 12H); 13C NMR
(100 MHz, CD2Cl2): d=139.3 (t, J=7.8 Hz), 135.9 (d, J=7.8 Hz), 132.5
(d, J=66.2 Hz), 132.2 (qd, 1J=32.7, 2J=10.9 Hz), 130.6, 130.4 (d, J=
9.3 Hz), 130.3 (dd, 1J=6.0, 2J=1.0 Hz), 129.4 (dt, 1J=11.9, 2J=3.6 Hz),
1
5.1 g (64.1%); white solid; H NMR (400 MHz, CDCl3): d=7.25–7.14 (m,
16H), 7.12 (t, J=8.0 Hz, 2H), 6.99–6.92 (m, 16H), 6.74 (d, J=8.0 Hz,
4H), 3.34 (d, J=13.6 Hz, 8H), 1.45–0.52 ppm (brs, 12H); 13C NMR
(100 MHz, CDCl3): d=163.1 (ddd, 1J=254.2, 2J=16.1 Hz, 3J=11.8 Hz),
138.1, 133.5 (dt, 1J=52.3, 2J=8.0 Hz), 132.1, 129.9 (dd, 1J=4.6, 2J=
1.5 Hz), 128.8, 115.1 (ddd, 1J=18.5, 2J=10.5, 3J=8.6 Hz), 107.8 (t, J=
24.9 Hz), 29.8 ppm (d, J=33.6 Hz); 19F NMR (376 MHz, CDCl3): d=
À105.2 ppm; 31P NMR (161 MHz, CDCl3): d=19.0 ppm; HRMS (ESI):
m/z: calcd for C64H50B4F16P4: 1290.298 [M]+; found: 1290.296.
1
2
129.2 (t, J=4.3 Hz), 128.8, 121.4 (qd, J=270.2, J=1.7 Hz), 30.6 ppm (d,
J=33.8 Hz); 19F NMR (376 MHz, CD2Cl2): d=À63.2 ppm; 31P NMR
(161 MHz, CD2Cl2): d=17.0 ppm; HRMS (ESI): m/z: calcd for
C72H58B4F24P4: 1546.3478 [M]+; found: 1546.3463.
Compound 1b: Prepared according to the typical procedure by using
complex 5b (1.3 g, 1.0 mmol) and DABCO (0.896 g, 8.0 mmol). Yield:
1
901 mg (73.0%); white solid; H NMR (400 MHz, CDCl3): d=7.10 (t, J=
7.6 Hz, 2H), 6.85–6.72 (m, 28H), 3.21 ppm (s, 8H); 13C NMR (100 MHz,
CDCl3): d=141.8, 138.3 (d, J=24 Hz), 135.6 (dd, 1J=5.5, 2J=3.2 Hz),
130.9, 129.1, 128.9 (q, J=2.8 Hz), 128.5, 128.2, 125.3, 115.4 (td, 1J=14,
2J=7.3 Hz), 105.0 (t, J=24.8), 35.0 ppm (q, J=5.8 Hz); 19F NMR
(376 MHz, CDCl3): d=À108.1 ppm; 31P NMR (146 MHz, CDCl3): d=
À11.1 ppm; HRMS (ESI): m/z: calcd for C64H39F16P4: 1235.8634
Compound 1e: Prepared according to the typical procedure by using
complex 5e (1.5 g, 1.0 mmol) and DABCO (0.896 g, 8.0 mmol). Yield:
1
954 mg (64.0%); white solid; H NMR (400 MHz, CDCl3): d=7.58 (t, J=
6.4 Hz, 8H), 7.48 (d, J=3.2 Hz, 8H), 7.42–7.33 (m, 16H), 6.98 (t, J=
7.6 Hz, 2H), 6.64 (d, J=7.6 Hz, 4H), 3.28 ppm (s, 8H); 13C NMR
(100 MHz, CDCl3): d=150.6, 139.4 (d, J=8.0 Hz), 138.4, 136.0 (d, J=
74.4 Hz), 134.1, 131.0 (q, J=32.7 Hz), 129.5 (d, J=20.8 Hz), 129.0, 128.6,
128.1, 127.9, 125.8 (d, J=3.7 Hz), 121.4 (q, J=397.7 Hz), 35.4 ppm (dd,
1J=33.8, 2J=5.1 Hz); 19F NMR (376 MHz, CDCl3): d=À62.8 ppm;
ACHTUNGTRENNUNG
[M+H]+; found: 1235.8623.
Complex 5c: Prepared according to the typical procedure by using di-
(p-trifluoromethylphenyl)phosphane (6.5 g, 20.3 mmol), nBuLi (2.5m in
hexane, 8.1 mL, 20.3 mmol), 2,2’,6,6’-tetrakis(chloromethyl)biphenyl (5c;
4942
www.chemeurj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 4938 – 4943

Tetraphosphane Ligands in Hydroformylation
FULL PAPER
31P NMR (146 MHz, CDCl3): d=À13.1 ppm; HRMS (ESI): m/z: calcd
for C72H47F24P4: 1491.2245 [M+H+]; found: 1491.2233.
ner, E. Herdtweck, P. Kiprof, Inorg. Chem. 1991, 30, 4271; c) C. P.
Casey, G. T. Whiteker, M. G. Melville, L. M. Lori, J. A. Gavney, Jr.,
D. R. Powell, J. Am. Chem. Soc. 1992, 114, 5535; d) W. A. Herr-
mann, R. Schmid, C. W. Kohlpaintner, T. Priermeier, Organometal-
lics 1995, 14, 1961; e) C. P. Casey, E. L. Paulsen, E. W. Beuttenmuel-
ler, B. R. Proft, L. M. Petrovich, B. A. Matter, D. R. Powell, J. Am.
Chem. Soc. 1997, 119, 11817.
Compound 1 f: The corresponding borane complex has poor solubility in
toluene and other commonly used solvents. Thus, this ligand was synthe-
sized directly without protection of the borane. Compound 1 f was pre-
pared according to the typical procedure by using di(3,5-ditrifluoro
ACHTUNGTNERmNUNG eth-
ACHTUNGTRENNUNGylphenyl)phosphane (3.7 g, 8.0 mmol), nBuLi (2.5m in hexane, 3.2 mL,
[3] Xantphos=4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; a) M.
Kranenburg, Y. E. M. van der Burgt, P. C. J. Kamer, P. W. N. M. van
Leeuwen, Organometallics 1995, 14, 3081; b) L. A. Van der Veen,
M. D. Boele, F. R. Bregman, P. C. Paul, P. W. N. M. van Leeuwen, K.
Goubitz, J. Fraanje, H. Schenk, C. Bo, J. Am. Chem. Soc. 1998, 120,
11616; c) J. J. Carbꢃ, F. Maseras, C. Bo, P. W. N. M. van Leeuwen, J.
Am. Chem. Soc. 2001, 123, 7630.
[4] Biphephos=2,2’-bis(diphenylphosphino)-1,1’-biphenyl; a) E. Billig,
A. G. Abatjoglou, D. R. Bryant, (UCC) US Patent 4769498, 1988;
b) G. D. Cuny, S. Buchwald, J. Am. Chem. Soc. 1993, 115, 2066.
8.0 mmol), and 2,2’,6,6’-tetrakis(chloromethyl)biphenyl (635.0 mg,
1.8 mmol). Yield: 3.0 g (81.7%); white solid; 1H NMR (400 MHz,
[D8]THF): d=8.10 (s, 8H), 7.77 (s, 16H), 7.21 (t, J=7.2 Hz, 2H), 6.88 (d,
J=7.2 Hz, 4H), 3.61 ppm (s, 8H); 13C NMR (100 MHz, [D8]THF): d=
141.8 (d, J=12.4 Hz), 139.4, 137.4, 134.0, 133.3 (q, J=35.1 Hz), 130.2 (d,
J=19.1 Hz), 124.8, 124.3 (q, J=271 Hz), 36.3 ppm (d, J=24.1 Hz);
19F NMR (376 MHz, [D8]THF): d=À64.3 ppm; 31P NMR (146 MHz,
C4D8O): d=À10.0 ppm; HRMS (ESI): m/z: calcd for C80H39F48P4:
2035.1236 [M+H+]; found: 2035.1231.
General procedure for the regioselective hydroformylation of terminal
olefins with 1: A 2 mL vial containing a magnetic stirring bar was
charged with ligand 1 (4 mmol) and [RhACHTNUGRTNE(NUG acac)(CO)2] (1 mmol in 0.1 mL
[5] Naphos=2,2’-bis[(diphenylphosphino)methyl]-1,1’-binaphthyl;
H.
Klein, R. Jackstell, K.-D. Wiese, C. Borgmann, M. Beller, Angew.
Chem. 2001, 113, 3505; Angew. Chem. Int. Ed. 2001, 40, 3408.
[6] R. Paciello, L. Siggel, M. Rçper, Angew. Chem. 1999, 111, 2045;
Angew. Chem. Int. Ed. 1999, 38, 1920.
[7] S. C. van der Slot, J. Duran, J. Luten, P. C. J. Kamer, P. W. N. M. van
Leeuwen, Organometallics 2002, 21, 3873.
[8] a) V. F. Slagt, J. N. H. Reek, P. C. J. Kamer, P. W. N. M. van Leeu-
wen, Angew. Chem. 2001, 113, 4401; Angew. Chem. Int. Ed. 2001,
40, 4271; b) B. Breit, W. Seiche, J. Am. Chem. Soc. 2003, 125, 6608;
c) V. F. Slagt, P. W. N. M. van Leeuwen, J. N. H. Reek, Angew.
Chem. 2003, 115, 5777; Angew. Chem. Int. Ed. 2003, 42, 5619;
d) V. F. Slagt, P. C. J. Kamer, P. W. N. M. van Leeuwen, J. N. H.
Reek, J. Am. Chem. Soc. 2004, 126, 1526; e) B. Breit, W. Seiche,
Angew. Chem. 2005, 117, 1666; Angew. Chem. Int. Ed. 2005, 44,
1640.
toluene). The mixture was stirred for 5 min then 1-octene (2 mmol) was
added followed by decane (0.1 mL) as the internal standard. Additional
toluene was added to bring the total reaction volume to 1 mL. The reac-
tion mixture was transferred to an autoclave, which was sealed and
purged with nitrogen three times and subsequently charged with CO
(10 atm) and H2 (10 atm). The autoclave was then heated to 1408C (oil
bath) and the pressure was adjusted to 20 atm. After 1 h, the autoclave
was taken out of the oil bath and cooled in ice-cold water. The pressure
was carefully released in a well-ventilated hood and the reaction mixture
was immediately analyzed by GC.
[9] A preliminary communication has been reported, see: Y. Yan, X.
Zhang, X. Zhang, Adv. Synth. Catal. 2007, 349, 1582–1586.
[10] a) D. Evrard, D. Lucas, Y. Mugnier, P. Meunier, J. C. Hierso, Orga-
nometallics 2008, 27, 2643–2653; b) J.-C. Hierso, M. Beaupꢄrin, P.
Meunier, Eur. J. Inorg. Chem. 2007, 3767–3780; c) J. C. Hierso,
R. V. Smaliy, R. Amardeil, P. Meunier, Chem. Soc. Rev. 2007, 36,
1754–1769; d) J. C. Hierso, R. Amardeil, E. Bentabet, R. Broussier,
B. Gautheron, P. Meunier, P. Kalck, Coord. Chem. Rev. 2003, 236,
143–206.
Acknowledgements
We thank the National Institutes of Health (GM58832) and Dow Chemi-
cal Inc. for financial support. The Bruker 400 MHz NMR spectrometer
used in these studies was purchased with grant no. 1S10RR023698-01A1
from the National Center for Research Resources (NCRR), a component
of NIH.
[11] a) Y. Yan, X. Zhang, X. Zhang, J. Am. Chem. Soc. 2006, 128, 16058;
b) S. Yu, Y. Chie, Z. Guan, X. Zhang, Org. Lett. 2008, 10, 3469–
3472; c) S. Yu, Y. Chie, Z. Guan, Y. Zou, W. Li, X. Zhang, Org.
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[12] I. Agranat, M. Rabinovitz, W. Shaw, J. Org. Chem. 1979, 44, 1936.
[13] The lithium diarylphosphane used was prepared in situ by the drop-
wise addition of the butyl lithium/hexane solution to the related di-
[1] For recent reviews and monographs, see: a) Rhodium-Catalyzed Hy-
droformylation (Eds.: C. Claver, P. W. N. M. van Leeuwen), Kluwer
Academic, Dordrecht, 2000; b) P. Pino, F. Piacenti, M. Bianchi in
Organic Syntheses via Metal Carbonyls (Eds.: I. Wender, P. Pino),
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Monoxide (Ed.: J. Falbe), Springer, Berlin, 1980, pp. 1–225; d) C. W.
Kohlpaintner, C. D. Frohning in Applied Homogeneous Catalysis
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Asymmetry 2004, 15, 2113–2122; h) B. Breit, W. Seiche, Synthesis
2001, 1.
AHCTUNGERTGaNNUN rylphosphanes, which were prepared according to Busaccaꢁs proto-
col: C. A. Busacca, J. C. Lorenz, N. Grinberg, N. Haddad, M. Hrap-
chak, B. Latli, H. Lee, P. Sabila, A. Saha, M. Sarvestani, S. Shen, R.
Varsolona, X. Wei, C. H. Senanayake, Org. Lett. 2005, 7, 4277–4280.
[2] Bisbi=2,2’-bis[diphenylphosphino]methyl)-1,1’-biphenyl;
a) T. J.
Devon, G. W. Phillips, T. A. Puckette, J. L. Stavinoha, J. J. Vander-
Received: November 12, 2009
bilt, US Patent 4694109, 1987; b) W. A. Herrmann, C. W. Kohlpaint-
Published online: March 25, 2010
Chem. Eur. J. 2010, 16, 4938 – 4943
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4943