ARTICLE IN PRESS
JID: CCLET
[m5G;September 4, 2021;16:2]
P. Gao, M. Ke, T. Ru et al.
Chinese Chemical Letters xxx (xxxx) xxx
Table 1
Table 2
Ligands screening for the Rh-catalyzed branched-selective hydroformylation of
styrene.a
Optimization of the Rh-catalyzed hydroformylation of styrene using L11 as the lig-
and.a
Entry
Ligand
t (h)
Yield of 11a (%)b
b/l (12a/13a)c
Entry
Rh/L
T (°C)
P
Solvent
Yield of
12a (%)b
b/l
(MPa)
(12a/13a)c
1
L1
24
24
24
24
24
24
24
24
24
24
24
24
24
24
12
12
12
60
49
21
42
75
84
26
76
23
44
92
74
85
56
91
72
74
8.5:1
8.4:1
8.4:1
6.5:1
3.0:1
5.4:1
3.8:1
3.2:1
10.1:1
4.8:1
11.3:1
2.8:1
5.9:1
10.4:1
10.1:1
10.0:1
2.8:1
1
2d
1/6
1/6
1/6
1/6
1/6
1/3
1/8
1/6
1/6
1/6
1/6
1/6
1/6
1/6
1/6
60
25
50
70
80
60
60
60
60
60
60
60
60
60
60
3.0
3.0
3.0
3.0
3.0
3.0
3.0
2.0
4.0
4.0
4.0
4.0
4.0
4.0
3.0
Tol./H2O
91
8
10.1:1
11.2:1
11.1:1
2.1:1
1.6:1
3.7:1
9.7:1
7.9:1
11.3:1
7.9:1
7.5:1
8.2:1
4.0:1
5.1:1
8:1
2
L2
Tol./H2O
3
L3
3
Tol./H2O
70
68
60
78
47
88
92
89
23
19
80
71
88
4
L4
4
Tol./H2O
5
L5
5
Tol./H2O
6
L6
6
Tol./H2O
7
L7
7
Tol./H2O
8
L8
8
Tol./H2O
9
L9
9
Tol./H2O
10
11
12
13d
14e
15f
16g
17
L10
L11
TPPTS
L11
L11
L11
L11
-
10
11
12
13
14
DCM/H2O
MTBE/H2O
Et2O/H2O
hexane/H2O
c-hexane/H2O
Tol./H2O
e
15
a
Reaction conditions: substrate (3.0 mmol), [Rh(COD)Cl]2 (0.05mol %), L11, or-
ganic solvent (15 mL)/H2O (15 mL), syngas (CO/H2 = 1:1), SDBS (0.86 mol %).
a
Reaction conditions: Styrene 11a (3.0 mmol), [Rh(COD)Cl]2 (0.05 mol%), lig-
and (0.6 mol%), toluene (15 mL), H2O (15 mL), syngas (CO/H2 = 1:1, 3.0 MPa),
24 h.
b
GC yield.
c
Determined by GC.
d
b
10% conversion.
GC yield.
e
c
The second recycle.
Determined by GC.
d
Rh(acac)(CO)2 (0.1 mol%).
e
RhCl3 (0.1 mol%).
f
0.86 mol% sodium dodecylbenzenesulfonate (SDBS) was used.
g
Absence of SDBS.
activity and regioselectivity of the Rh-catalyzed styrene hydro-
formylation was investigated. Notably, the activity and regioselec-
tivity of the reaction had obvious temperature effect. Lowering
the temperature from 60 °C to 25 °C under standard condition
(toluene/H2O (1:1), 3.0 MPa CO/H2 (1:1), 0.86 mol% SDBS) dramat-
ically reduced the yield to 8% within 12 h (entry 1 vs. 2). Perform-
ing the reaction at 50 °C revealed an improved yield of 70% with
good regioselectivity (b/l = 11.1:1, entry 3) with full conversion in
12 h. At temperature over 60 °C, the regioselectivity and yield for
the branched 12a was also significantly reduced (68%, b/l = 2.1:1
at 70 °C; 60%, b/l = 1.6:1 at 80 °C; entries 4 and 5). Increasing
or decreasing the molar ratio of Rh/ligand L11 distinctly impaired
the yield and regioselectivity for this transformation. A decrease
of the Rh ligand L11 molar ratio from 1:6 to 1:3 led to low re-
gioselectivity (b/l = 3.7:1, entry 1 vs. 6). Moreover, further increas-
ing the molar ratio of Rh/ligand L11 to 1:8 produced a significant
rise in regioselectivity (b/l = 9.7:1), but with poor yield (47%, en-
try 7). Varying pressure of syngas (CO/H2 = 1:1) did not retard the
rate but did alter the selectivity towards branched-selective prod-
uct. Reducing the syngas pressure to 2.0 MPa resulted in a decrease
in branched aldehyde 12a from b/l = 10.9:1 to 7.9:1 (entry 1 vs. 8).
A slightly increase in yield and regioselectivity was observed when
4.0 MPa syngas pressure was used for this transformation (entry
9). In addition, the use of other organic/aqueous biphasic systems,
suh as DCM/H2O, MTBE/H2O, hexane/H2O, cyclohexane/H2O, was
found to be less effective than toluene/H2O (entries 10-14). After
reaction conditions were screened, the Rh-catalyzed hydroformy-
lation reaction was performed using L11 as a ligand under 4.0
MPa of syngas (CO/H2, 1:1) at 60 °C in toluene/H2O (1:1) bipha-
sic system in the presence of 0.86 mol% SDBS. Optimized conver-
sion, yield for branched aldehyde 12a, and regioselectivity were
achieved under this reaction conditions. The water-soluble Rh/L11
catalyst can be readily recycled by simple phase separation and
still gave 88% yield of 12a in the second run (entry 15).
The dicarboxylated PNP ligand L5 gave better yield (75%, entry 5)
compared with results of monocarboxylated PNP ligands (L1-L4),
but with poor regioselectivity (b/l = 3.0:1). Moreover, the mono-
carboxylated PNP ligand L6 with a biphenyl ring resulted in much
higher yield (84%), albeit with a ratio of 12a/13a of 5.4:1 (entry
6). The sulfonated PNP ligand L7 with meta-SO3Na gave poor yield
and regioselectivity (26%, b/l = 3.8:1, entry 7) under identical con-
ditions. The ligand L8 bearing meta-SO3Na and para-MeO groups
of phenyl ring was shown to give superior yield of 12a, but much
worse regioselectivity (12a/13a = 3.2:1) was obtained (entry8). A
change of the position of SO3Na group on ligand L7 from meta- to
para-position resulted in similar yield (entry 9), but high regiose-
lectivity compared with the results of the corresponding sulfonated
PNP ligand L7-L10. The use of ligand L11 with ortho-SO3Na group
on phenyl ring afforded branched aldehyde 12a in 92% yield with
high regioselectivity (b/l = 11.3:1, entry 11). The well-known TPPTS
only gave 74% yield of 12a, with poor regioselectivity (b/l = 2.8:1,
entry 12) under identical conditions. Other common Rh catalysts
for hydroformylation, such as Rh(acac)(CO)2) and RhCl3, low re-
gioselectivities and reactivities were respectively obtained (entries
13 and 14). Addition of SDBS (0.86 mol%) as the surfactant could
short reaction time to 12 h, and provide branched 12a in 91% yield
and a 10.1:1 ratio of b/l (entry 15). Branched product was obtained
in 72% yield with 10.0:1 ratio of b/l in absence of SDBS (Table 1,
entry 16). The control experiment of absence of ligand was also
carried out to give the product in 74% yield with 2.8:1 ratio b/l (en-
try 17). These results revealed the crucial role of these two types
of ligand structures in controlling of yield and regioselectivity for
this Rh-catalyzed hydroformylation reaction.
With the best ligand L11, a series of Rh-catalyzed styrene hy-
droformylation parameters were examined, including temperature,
Rh/ ligand L11 molar ratio, organic/aqueous biphasic system, and
CO/H2 pressure (Table 2). First, the temperature impacted on the
3