Highly regioselective hydroformylation of 1,5-hexadiene to linear dialdehyde catalyzed by rhodium complexes with tetraphosphorus ligands

Article abstract of DOI:10.1016/j.tetlet.2009.07.066

Rhodium-catalyzed hydroformylation of 1,5-hexadiene to corresponding dialdehydes was investigated using tetraphosphorus ligands. These ligands showed a high regioselectivity for linear aldehydes (linear to branch ratio up to 98%) in very good yield (up to 87%). It was found that the introduction of the substituents at the ortho position of the biphenyl moiety has little effect on the regioselectivity and the electron-donating substituents retard the reaction somewhat.

Full text of DOI:10.1016/j.tetlet.2009.07.066

Tetrahedron Letters 50 (2009) 5575–5577
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Tetrahedron Letters
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Highly regioselective hydroformylation of 1,5-hexadiene to linear
dialdehyde catalyzed by rhodium complexes with tetraphosphorus ligands
Shichao Yu a, Yu-ming Chie a, Xiaowei Zhang a, Liyan Dai b, Xumu Zhang a,
*
a Department of Chemistry and Chemical Biology and Department of Pharmaceutical Chemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
b College of Materials Science and Chemical Engineering, Zhejiang University, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Rhodium-catalyzed hydroformylation of 1,5-hexadiene to corresponding dialdehydes was investigated
using tetraphosphorus ligands. These ligands showed a high regioselectivity for linear aldehydes (linear
to branch ratio up to 98%) in very good yield (up to 87%). It was found that the introduction of the sub-
stituents at the ortho position of the biphenyl moiety has little effect on the regioselectivity and the elec-
tron-donating substituents retard the reaction somewhat.
Received 7 July 2009
Revised 11 July 2009
Accepted 14 July 2009
Available online 18 July 2009
Ó 2009 Published by Elsevier Ltd.
Keywords:
Hydroformylation
Rhodium
Dialdehyde
Phosphorus ligand
Hydroformylation of alkenes represents a highly attractive
method to prepare aldehydes and alcohols, and is one of the most
important reactions in industry catalyzed by homogeneous cata-
lysts. Production is estimated over 9 million tons annually.1 Many
efforts have been devoted to the development of systems with im-
proved regioselectivity toward the formation of the industrially
more important linear aldehydes.2 Both phosphine- and phos-
phite-based systems giving high regioselectivities to linear alde-
hydes for the hydroformylation of terminal and internal alkenes
have been reported.3 Recently, there has been increased interest
in the regioselective hydroformylation of ready available function-
alized alkenes.4 One of such cheap, useful feedstock is 1,n-diolefins.
Double hydroformylation of 1,n-diolefins would produce dial-
dehydes, which are valuable intermediates for the preparation of
a variety of commercially important products such as bicarboxylic
acids and their derivatives,5 diamines,6 alicyclic, and heterocyclic
compounds having different structures.7 Particularly important is
the use of the dialdehydes as cross-linking agents for polymers
such as proteins,8 polysaccharides,9 and other functionalized mac-
romolecular compounds.10 However, only in particular cases this
method appears capable to give acceptable results. In most cases,
a complex mixture of monoaldehydes and dialdehydes, arising
from the consequent hydroformylation–isomerization–hydrofor-
mylation of the two double bonds was obtained, which made this
process less practical (1,5-hexadiene as example, Scheme 1).
In 1964 Morikawa reported some interesting results concerning
the oxo-reaction on 1,4-pentadiene and 1,5-hexadiene: the yield of
linear dialdehydes, however, did not exceed 40% and in some cases
the formed pimelaldehyde is transformed in the reaction medium
CHO
CHO
9
8
7
olefin
olefin
isomeri-
zation
isomeri-
zation
CHO
olefin
CHO
6
olefin
isomeri-
zation
isomeri-
zation
hydroformylation
CHO
CHO
1
2
hydrofor-
mylation
hydrofor-
mylation
CHO
4
CHO
CHO
CHO
OHC
3
5
CHO
* Corresponding author. Fax: +1 732 445 6312.
E-mail address: xumu@rci.rutgers.edu (X. Zhang).
Scheme 1. Hydroformylation of 1,5-hexadiene.
0040-4039/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2009.07.066

5576
S. Yu et al. / Tetrahedron Letters 50 (2009) 5575–5577
starting material was almost completely consumed. A mixture of
L1
L2
L3
L4
L5
L6
L7
R = H
olefin isomers (formed via the isomerization of the carbon–carbon
double bond of the original diolefins, 1,4-hexadiene was the main
isomer), monoaldehydes (6-hepten-1-al 1 and 2-methyl-5-hexen-
1-al 2, and isomers 6–9 from the migration of the double bond of
the original monoaldehydes 1 and 2, 6 was the main isomer) and
dialdehyde compounds (1,8-octanedial 3, 2-methyl-1,7-heptane-
dial 4, and 2,5-dimethyl-1,6-hexanedial 5) was obtained in 14.4%,
11.5% (1/2 = 96.3/3.7), 26.2%, and 47.9% (3/4/5 = 94.1/5.3/0.6)
yields, respectively. The effect of syngas pressure was then investi-
gated. It was found that the syngas pressure has a significant influ-
ence on the yield of dialdehydes (entries 2–5). With the increased
pressure from 10 (CO/H2 = 1) to 80 atm (CO/H2 = 1), the amounts of
olefin isomers and monoaldehydes decreased steadily, along with
the increasing yield of the dialdehydes (up to 87%). Meanwhile,
the product distribution almost not changed under the reaction
conditions used. It was also found that the decrease of temperature
from 100 °C to 60 °C has little effect on the product distribution
(entries 6 and 7).
Based on the optimal reaction condition for ligand L1 (100 °C,
H2/CO = 40/40 atm, t = 2 h), 1,5-hexadiene was then hydroformy-
lated using the complex formed in situ from Rh(acac)(CO)2 and
L2–L7. The results are summarized in Table 2. In our previous stud-
ies, we have found that the introduction of substituents at the
3,30,5,50-position of the biphenyl moiety would greatly increase
the regioselectivity for the linear aldehydes.13b,c Surprisingly, the
effect of these substituents on the regioselectivities was not as
remarkable as observed before. In all the cases, a high linear to
branch ratio was obtained for both the monoaldehydes and the
dialdehydes. This phenomenon may hint that the big natural bite
instead of the steric of the biphenyl moiety controlled the regiose-
lectivity. However, these substituents did have some effects on the
yields of dialdehydes 6–9, which decreased with the introducing of
electron-donating groups such as Me, Et, and p-MePh (Table 2, en-
tries 2–4 and 6).
R = Cl
N
P
N R
R
R = Me
R = Et
P
N
N
N
O
O
O
P
O
R = Ph
R = p-F-Ph
R = Tolyl
N
P
N
N R
R
Scheme 2. Ligands used in this study.
into cyclohexancarboxaldehyde through intramolecular aldol con-
densation.5 Later, other groups investigated this reaction using dif-
ferent catalytic systems or in special reaction media.11 The real
breakthrough was made by Marchetti who found that 1,5-hexadi-
ene could be converted to the corresponding linear dialdehydes
selectively in over 80% yield when RhH(CO)(PPh)3 was combined
with Xanphos.12 Other methods known to transform various func-
tionalities into the aldehyde group, which has been successfully
used for the preparation of monoaldehydes, only in a few cases
can be conveniently extended to the preparation of dialdehydes.
The chemoselectivities are often unsatisfactory due to the forma-
tion of other products such as cyclic lactones and other side reac-
tions. Thus, it is highly desirable to develop new, economic, and
efficient process for the synthesis of linear dialdehyde.
Recently, we have reported the synthesis and application of a
class of new tetraphosphorus ligands (Scheme 2), which showed
to promote an exceptionally high regioselectivity toward the for-
mation of linear aldehydes in the rhodium-catalyzed hydroformyl-
ation of olefins.13 The peculiar behavior of these ligands was
ascribed to the large ‘natural’ bite angle formed by coordination
with the metal (nine-member ring), the multiple coordination
modes keeping the formation of the selective catalytic species in
the greatest degree,14 and the electron-withdrawing property of
N-pyrrolylphosphorus moiety.15 The high regioselectivity and
reactivity prompted us to assess our ligands further in the hydro-
formylation of 1,n-diolefins. Herein, we wish to disclose our recent
studies on the hydroformylation of 1,5-hexadiene.
In summary, we have shown that the hydroformylation of 1,5-
hexadiene can be achieved with essentially high regioselectivity
(linear selectivity is up to 98%) by using tetraphosphorus-based
Rhodium catalyst. It was found that the introducing of the substit-
uents at the ortho position of the biphenyl moiety has little effect
on the regioselectivity and the electron-donating substituents re-
tard the reaction somewhat. Further ligands applications and
mechanism studies are now under investigation and will be re-
ported in due course.
Initially, 1,5-hexadiene was subjected to rhodium-catalyzed
hydroformylation in toluene at 100 °C and 10 atm (CO/H2 = 1) for
2 h using ligand L1 (Table 1).16 Under this reaction condition, the
Table 1
Hydroformylation of 1,5-hexadiene using ligand L1 under different reaction conditionsa
Entry
Pressure H2/CO (atm)
Temperature (°C)
Conv.b (%)
Yield (%)
Olefin isomerc (%)
Monoaldehydes
1+2 (1/2)d
Dialdehydes 3+4+5 (3/4/5)f
6–9e
1
2
3
4
5
6
7
5/5
100
100
100
100
100
80
>99
>99
>99
>99
>99
>99
>99
14.4
3.3
1.2
<1
<1
<1
11.5(96.3/3.7)
7.4(96.8/3.4)
4.7(97.1/2.9)
3.5(97.2/2.8)
5.6(96.2/3.8)
3.6(97.4/2.6)
6.0(97.6/2.4)
26.2
17.9
13.5
8.2
6.3
8.3
47.9(94.1/5.3/0.6)
71.3(95.2/4.3/0.5)
80.6(96.7/2.9/0.4)
87.3(97.4/2.3/0.3)
87.6(97.4/2.3/0.3)
87.4(97.4/2.3/0.3)
86.8(97.5/2.2/0.2)
10/10
20/20
30/30
40/40
40/40
40/40
60
<1
6.7
a
S/C = 1,000, Rh/L = 4/1, [Rh] = 1.0 mM, t = 2 h, toluene as solvent, decane as internal standard. The oxo-products were identified by GC–mass spectroscopy. Compound 1:
MS: m/z (%) 39 (47), 41 (100), 42 (32), 43 (31), 55 (45), 67 (49), 68 (78), 79 (30). 81 (16), 86 (11), 112 (1). Compound 2: MS: m/z (%) 41 (88), 55 (58), 57 (27), 58 (100), 112 (2).
Compound 3: MS: m/z (%) 41 (100), 42 (27), 43 (61), 44 (65), 54 (41), 55 (67), 57 (88), 80 (26), 81 (79), 98 (13), 110 (17), 142 (5). Compound 4: MS: m/z (%) 41 (100), 43 (69), 55
(35), 57 (60), 58 (83), 69 (29), 112 (15), 124 (21), 142 (2). Compound 5: MS: m/z (%) 41 (61), 43 (100), 55 (67), 57 (49), 58 (77), 71 (40), 84 (51), 96 (21), 124 (14), 142 (1).
b
Conversion of 1,5-hexadiene, determined on the basis of GC.
The yield of 1,5-hexadiene isomerization products, determined on the basis of GC.
Determined on the basis of GC analysis.
Total yield of the monoaldehydes 6, 7, 8, and 9.
c
d
e
f
Determined on the basis of GC.

S. Yu et al. / Tetrahedron Letters 50 (2009) 5575–5577
5577
Table 2
Hydroformylation of 1,5-hexadiene using ligand L2–L7 under optimized pressure and temperaturea
Entry
L
Yield (%)
Olefin isomerb (%)
Monoaldehydes
Dialdehydes 3+4+5 (3/4/5)e
1+2 (1/2)c
6–9d
1
2
3
4
5
6
L2
L3
L4
L5
L6
L7
<1
<1
<1
<1
<1
<1
8.0 (96.2/3.6)
4.6 (96.8/3.2)
8.3 (95.9/4.1)
8.9 (94.9/5.1)
8.0 (97.4/2.6)
11.1 (95.0/5.0)
8.7
17.9
12.1
10.5
8.7
82.1 (97.5/2.2/0.3)
76.9 (98.1/1.7/0.2)
78 (98.3/1.4/0.3)
79.1 (97.7/2.0/0.3)
81.7 (96.8/2.9/0.3)
67.8 (96.7/3.0/0.3)
16.9
a
S/C = 1,000, Rh/L = 4/1, [Rh] = 1.0 mM, 100 °C, H2/CO = 40/40 atm, t = 2 h, conversion >99%, toluene as solvent, decane as internal standard.
See Table 1.
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Acknowledgments
We thank the National Institutes of Health (GM58832) and Dow
Chemical Inc. for financial support.
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16. Experimental: A 2-mL vial with a magnetic stirring bar was charged with
ligand L1 (4
lmol, 3.6 mg) and Rh(acac)(CO)2 (1 lmol, 0.1 mL of 10 mM
solution in toluene). The mixture was stirred for 5 min, 1,5-
hexadiene(1.0 mmol, 0.12 mL) was then added, followed by decane (0.1 mL)
as internal standard and toluene (0.68 mL). The reaction mixture was
transferred to an autoclave. The autoclave was purged with nitrogen three
times and subsequently charged with CO (40 atm) and H2 (40 atm). The
autoclave was then heated to 100 °C and the pressure was set to 80 atm. After
2 h, the autoclave was cooled in icy water, and the pressure was carefully
released in a well-ventilated hood. The reaction mixture was immediately
analyzed by GC to determine the conversion and regioselectivity.