Chemoselectivity in the rhodium-catalyzed hydroformylation of 4-vinylpyridine: Crucial role of phosphine ligand in promoting carbonylation instead of hydrogenation

Article abstract of DOI:10.1016/S0022-328X(00)00011-5

Hydroformylation of 4-vinylpyridine (4VP) in benzene with Rh₄(CO)₁₂/PMe₂Ph or Rh₄CO₁₂ as catalytic precursor shows completely different chemoselectivity, carbonylation product (branched aldehyde) largely prevailing with the first catalyst, hydrogenation product 4-ethylpyridine (4EP) with the second one. Different phosphines and P/Rh ratios were also used, and a comparison with 3-vinylpyridine (3VP) under the same experimental conditions was made too. In all the experiments 3VP exclusively gives aldehidic products. In the case of 4VP, hydrogenation prevails on carbonylation at low P/Rh ratio (<0.5), while for higher values more than 80% of carbonylation product is obtained. The strong electron-donor phosphine ligand changes the polarization of the carbon-rhodium bond making this carbon suitable for the migratory insertion process and hence determining the acyl-metal intermediate formation precursor of the aldehyde.

Full text of DOI:10.1016/S0022-328X(00)00011-5

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Journal of Organometallic Chemistry 599 (2000) 298–303
Chemoselectivity in the rhodium-catalyzed hydroformylation of
4-vinylpyridine: crucial role of phosphine ligand in promoting
carbonylation instead of hydrogenation
Aldo Caiazzo a, Roberta Settambolo b, Lorenzo Pontorno a, Raffaello Lazzaroni a,*
a Dipartimento di Chimica e Chimica Industriale, Centro di Studio CNR per le Macromolecole Stereordinate ed Otticamente Atti6e,
6ia Risorgimento 35, I-56126 Pisa, Italy
b Dipartimento di Chimica e Chimica Industriale, Istituto di Chimica Quantistica ed Energetica Molecolare del CNR, 6ia Risorgimento 35,
I-56126 Pisa, Italy
Received 5 October 1999; accepted 3 January 2000
Abstract
Hydroformylation of 4-vinylpyridine (4VP) in benzene with Rh4(CO)12/PMe2Ph or Rh4CO12 as catalytic precursor shows
completely different chemoselectivity, carbonylation product (branched aldehyde) largely prevailing with the first catalyst,
hydrogenation product 4-ethylpyridine (4EP) with the second one. Different phosphines and P/Rh ratios were also used, and a
comparison with 3-vinylpyridine (3VP) under the same experimental conditions was made too. In all the experiments 3VP
exclusively gives aldehidic products. In the case of 4VP, hydrogenation prevails on carbonylation at low P/Rh ratio (B0.5), while
for higher values more than 80% of carbonylation product is obtained. The strong electron-donor phosphine ligand changes the
polarization of the carbonꢀrhodium bond making this carbon suitable for the migratory insertion process and hence determining
the acyl–metal intermediate formation precursor of the aldehyde. © 2000 Elsevier Science S.A. All rights reserved.
Keywords: Hydroformylation; Phosphines; Vinylpyridines; Rhodium; Chemoselectivity; Catalysis
1. Introduction
We recently reported that the rhodium-catalyzed hy-
droformylation of 4-vinylpyridine (4VP) led to the ex-
clusive formation of 4-ethylpyridine (4EP); this result
was in contrast to the one that observed for 3-
vinylpyridine (3VP), whose hydroformylation under the
same experimental conditions gave the corresponding
aldehydic branched isomer 3a with very high chemo-
and regioselectivity [8] (Scheme 1). The different behav-
ior of the two vinylpyridine isomers was explained on
the basis of the different charge density on 3- and 4-
positions in the pyridine ring, which influences the
polarity of the carbon-rhodium bond in the branched
alkyl–rhodium intermediates, determining their differ-
ent evolution [8].
As in the above investigation unmodified Rh4(CO)12
was used as catalytic precursor, it was interesting to see
if in the case of 4VP the use of rhodium catalytic
systems modified with an auxiliary phosphorus ligand
(L) could vary the electronic situation onto the alkyl
metal intermediates and then encourage the formation
The rhodium-catalyzed hydroformylation of unsatu-
rated substrates usually gives aldehydic products with a
high chemoselectivity [1]. This occurs both with
aliphatic substrates, such as 1-hexene [2], and aromatic
ones, such as styrenes [3], vinylfurans [4] and
vinylpyrroles [5], whose hydroformylation almost exclu-
sively gives the expected aldehydic products.
Nevertheless there are some exceptions to this trend,
such as a,b-unsaturated aldehydes and ketones that
undergo only a hydrogenation process under oxo con-
ditions [6]. Also vinylidenic olefins containing one or
two pyridyl moieties give rise to a relatively high
amount of hydrogenation product when they are hy-
droformylated in the presence of rhodium catalysts [7].
The reason for this behavior is still obscure.
* Corresponding author. Tel.: +39-50-918227; fax: +39-50-
918260.
E-mail address: lazza@dcci.unipi.it (R. Lazzaroni)
0022-328X/00/$ - see front matter © 2000 Elsevier Science S.A. All rights reserved.
PII: S0022-328X(00)00011-5

A. Caiazzo et al. / Journal of Organometallic Chemistry 599 (2000) 298–303
299
60–120°C, by using P/Rh=4. The results obtained are
summarized in Tables 1 and 2 and in Fig. 1. Analogous
experiments carried out on 3VP are reported in Tables
1 and 2.
A set of experiments was carried out on 4VP in the
presence of Rh4(CO)12 modified with various phospho-
rus ligands (P/Rh=6), differing from each other in
electronic properties and steric hindrance. All the reac-
tions were carried out at 100°C and at 110 atm gas
pressure (CO/H2=1:1). The results obtained are sum-
marized in Table 3.
It was observed that the reaction times were shorter
than those observed in the case of unmodified
Rh4(CO)12 for both the substrates, but they tend to
increase with the increase of P/Rh ratio.
Scheme 1.
For 4VP, by increasing the P/Rh ratio, the amount
of the hydrogenation product 4-ethylpyridine (4EP)
quickly decreases from 70% at P/Rh=0.25 to 15% at
P/Rh=2, reaching 10% at P/Rh=9, whilst the per-
centage of the branched aldehyde 4a on the total of
aldehydic products is always very high, rising from 92%
at P/Rh=0.25 to 98% at P/Rh=2 and being constant
for higher ratios. The reaction selectivity does not
change with increasing temperature, at least in the
range 60–120°C (P/Rh=4). All the phosphorus ligands
used give a chemoselectivity into aldehydic products
greater than 80% and a regioselectivity into branched
aldehyde 4a greater than 95% for most cases, not
significantly depending on the electronic and steric
character of the phosphine.
For 3VP, by increasing the P/Rh ratio, the chemose-
lectivity into aldehydic products always stays very high
(ca. 99%), while the a-regioselectivity tends to increase
from 86% at P/Rh=0 to 96% at P/Rh=6 (see Table
4). Also for this isomer, the increase of temperature at
a fixed P/Rh ratio (P/Rh=4) does not affect the selec-
tivity of the process.
Scheme 2.
of the corresponding aldehydic products, instead of
hydrogenation compounds. Different phosphines and
P/Rh ratios were used in order to determine their
influence on the selectivity of the process. 3-
Vinylpyridine was also investigated under the same
experimental conditions; the purpose was to compare
the reciprocal behavior of these vinylpyridine isomers,
characterized by the above-mentioned different elec-
tronic situations [8].
We surprisingly found that in the presence of phos-
phorus ligands, 4VP gave a high chemoselectivity into
aldehydes and an almost complete regioselectivity into
the branched isomer 4a (Schemes 2 and 3, Fig. 1). In
these conditions 3VP and 4VP behaved in a very
similar manner.
2-(4-pyridyl)propanal (4a), the predominant isomer,
1
has been identified from the H-NMR spectrum of the
crude hydroformylation mixture1. 3-(4-pyridyl)propanal
(4b), the minor product of the reaction, has been char-
acterized by comparison with an authentic sample ob-
tained by oxidation of 3-(4-pyridyl)propanol [9]2. The
aldehydes 3a and 3b, deriving from the hydroformyla-
tion of 3VP, had already been characterized in a previ-
ous work [8].
2. Results
The hydroformylation reactions were carried out in
benzene at partial substrate conversion, in a stainless
steel autoclave, using Rh4(CO)12 as catalyst precursor,
both in the absence and in the presence of phosphines.
The composition of the reaction mixtures was evaluated
by GC analysis, using o-xylene as internal standard.
A set of runs was carried out for 4VP with
Rh4(CO)12 in the presence of PMe2Ph by varying the
P/Rh ratio. This ranged from 0.25 to 9, at 100°C and
110 atm total pressure (CO/H2=1:1). The reaction was
also investigated at different temperatures, in the range
1 1H-NMR spectrum of 4a in C6D6 (TMS) shows as characteristic
signals a doublet at 0.92 ppm (CH3), a quartet at 2.80 ppm (CH) and
a doublet at 9.12 ppm (CHO); any attempt at isolation through the
usual techniques (distillation, liquid chromatography, etc.) failed
because of its instability.
2 1H-NMR spectrum of 4b in C6D6 shows as characteristic signals
two triplets at 2.05 ppm and at 2.36 ppm, respectively (CH2) and a
doublet at 9.19 ppm (CHO).

300
A. Caiazzo et al. / Journal of Organometallic Chemistry 599 (2000) 298–303
Scheme 3.
Fig. 1. Rhodium-catalyzed hydroformylation of 4-vinylpyridine (4VP) at complete substrate conversion in the presence of Rh4(CO)12/PMe2Ph as
catalyst precursor: influence of P/Rh ratio on the reaction selectivity.
3. Discussion and conclusions
In a previous paper [8] on the hydroformylation of
3VP and 4VP it was clearly emphasized that in the
presence of unmodified Rh4(CO)12 4VP almost exclu-
sively gives the hydrogenation of the olefinic double
bond instead of the carbonylation process. This behav-
The dramatic change of chemoselectivity caused by
ior was attributed to the electron-poor character of the
the addition of a phosphine ligand is likely due to the
pyridine ring and, in particular, to the high positive
increase of RhꢀC bond polarization. Indeed the induc-
charge localized on the position 4 (CNDO calculations)
[10]. This feature determines a strong decrease of the
nucleophilic character of the carbon bonded to the
rhodium, which is not able to give the migratory inser-
tion on the CO coordinated to the metal and hence
undergoes only a slow dihydrogen addition.
tive electron-donor effect of phosphine could be trans-
mitted through the rhodium to the adjacent carbon,
which becomes sufficiently nucleophilic to give the mi-
gratory insertion on CO, hence evolving to the acyl
intermediate, precursor of the branched aldehyde (4a).
In addition it should be pointed out that a high

A. Caiazzo et al. / Journal of Organometallic Chemistry 599 (2000) 298–303
301
Table 1
Rhodium-catalyzed hydroformylation of vinylpyridine isomers (nVP) at complete substrate conversion in the presence of Rh4(CO)12/PMe2Ph as
catalyst precursor: influence of P/Rh ratio on products distribution a
Substrate
P/Rh
Time (min)
Hydrogenation b (yield%)
Hydroformylation b (yield%)
a:b b
3VP
3VP
3VP
3VP
4VP
4VP
4VP
4VP
4VP
4VP
4VP
4VP
4VP
0
1
3
6
120
20
45
200
240
71
30
15
30
40
1
1
1
99
99
99
99
2
30
47
81
85
85
85
87
90
86:14
91:9
95:5
96:4
30:70
92:8
95:5
97:3
98:2
98:2
98:2
98:2
98:2
1
0
98
70
53
19
15
15
15
13
10
0.25
0.5
1
2
3
4
6
9
60
60
70
a Reaction conditions: 4.64 mmol of nVP, 5 ml of benzene, 0.004 mmol of Rh4(CO)12; autoclave volume 25 ml; 100°C temperature; 110 atm
total pressure (1:1 H2/CO).
b Percentage determined via GC on the total reaction products of the crude reaction mixtures, using o-xylene as internal standard.
Table 2
Rhodium-catalyzed hydroformylation of vinylpyridine isomers (nVP), at complete substrate conversion at different temperatures in the presence
of Rh4(CO)12/PMe2Ph as catalyst precursor a
Substrate
Temperature
Time (min)
Hydrogenation b (yield%)
Hydroformylation b (yield%)
a:b b
3VP
3VP
3VP
3VP
4VP
4VP
4VP
4VP
60
80
100
120
60
80
100
120
960
420
120
60
600
60
1
1
1
99
99
99
99
84
84
85
85
96:4
96:4
95:5
95:5
99:1
98:2
98:2
97:3
1
16
16
15
15
60
20
a Reaction conditions: 4.64 mmol of nVP, 5 ml of benzene, 0.004 mmol of Rh4(CO)12, 0.064 mmol of PMe2Ph (P/Rh=4); autoclave volume
25 ml; 110 atm total pressure (1:1 H2/CO).
b Percentage determined via GC on the total reaction products of the crude reaction mixtures, using o-xylene as internal standard.
Table 3
Rhodium-catalyzed hydroformylation of 4-vinylpyridine (4VP) at complete substrate conversion in the presence of Rh4(CO)12 modified with
different phosphorus ligands a
Phosphorus ligand
Time (min)
Hydrogenation b yield (%)
Hydroformylation b yield (%)
4a:4b b
PPh3
30
35
55
60
30
30
30
50
9
10
13
12
12
11
20
9
91
90
87
88
88
81
80
91
95:5
96:4
98:2
98:2
96:4
96:4
96:4
98:2
PMePh2
PMe2Ph
PMe3
PEt3
P(nBu)3
DPPE
DPPP
a Reaction conditions: 4.64 mmol of 4-vinylpyridine, 5 ml of benzene, 0.004 mmol of Rh4(CO)12, 0.096 mmol of P (P/Rh=6); autoclave volume
25 ml; 100°C temperature; 110 atm total pressure (1:1 H2/CO).
b Percentage determined via GC on the total reaction products of the crude reaction mixtures, using o-xylene as internal standard.
chemoselectivity into aldehydes (always greater than
80%) is also observed by using other phosphines, show-
ing that this is a general trend due to the well-known
s-donor property of phosphorus ligands.
In the case of 3VP the positive charge density on
position 3 of the pyridine ring is much lower [10] so the
carbon atom in RhꢀC bond is sufficiently nucleophilic
both with unmodified and phosphine-modified

302
A. Caiazzo et al. / Journal of Organometallic Chemistry 599 (2000) 298–303
Table 4
Rhodium-catalyzed hydroformylation of vinylpyridine isomers (nVP) and styrene at complete substrate conversion: a comparison between
Rh4(CO)12 and Rh4(CO)12/PMe2Ph a
Substrate
Catalyst precursor
Time (min)
Hydrogenation b (yield%)
Hydroformylation b (yield%)
a:b b
Styrene
3VP
4VP
Styrene
3VP
4VP
[Rh]
[Rh]
[Rh]
[Rh/L]
[Rh/L]
[Rh/L]
20
120
240
60
45
60
1
1
98
1
1
15
99
99
2
99
99
85
79:21
86:14
30:70
94:6
96:4
98:2
a Reaction conditions: 4.64 mmol of substrate, 5 ml of benzene, 0.004 mmol of Rh4(CO)12, 0.064 mmol of PMe2Ph (L) (P/Rh=4); 100°C
temperature; autoclave volume 25 ml; 110 atm total pressure (1:1 H2/CO).
b Percentage determined via GC on the total reaction products of the crude reaction mixtures, using o-xylene as internal standard.
Rh4(CO)12. Thus the chemoselectivity into aldehydic
products is always almost complete.
4.1. Hydroformylation of 6inylpyridines: general
procedure
The high a-regioselectivity observed for the branched
aldehydic isomers 4a and 3a should derive from the
preferential formation of the branched alkyl–metal in-
termediates with respect to the linear ones, due to the
electron-withdrawing character of the pyridine ring.
This feature had already been discussed in a previous
paper on the hydroformylation of styrene [3] and
vinylpyridines [11].
The results summarized in Table 2 indicate that
temperature does not affect the selectivity of the reac-
tion in the presence of phosphine either with 4VP or
with 3VP. This could be explained taking into account
what has already been reported in the case of styrene
and of vinylpyrroles: it is likely that the presence of
phosphine ligands on the metal inhibits the b-hydride
elimination process and hence prevents the interconver-
sion of alkyl–metal species. So the isomeric ratio be-
tween the aldehydic products directly reflects the one of
isomeric alkyl–rhodium intermediates [3].
A solution of nVP (0.5 ml, 4.64 mmol), Rh4(CO)12 (3
mg, 0.004 mmol), phosphine (corresponding to the
desired P/Rh molar ratio) and o-xylene (0.5 ml) in
benzene (5 ml) was introduced by suction into an
evacuated 25 ml stainless steel autoclave. Carbon
monoxide was introduced, the autoclave was stirred
and heated to 100°C, and dihydrogen was rapidly intro-
duced up to 110 atm total pressure (CO/H2 =1:1).
When the gas absorption reached the value correspond-
ing to the desired conversion, the reaction mixture was
siphoned out. The degree of conversion was measured
by GLC analysis, using o-xylene as internal standard.
Acknowledgements
This work was supported by the Ministero dell’
Universita` e della Ricerca Scientifica e Tecnologica
(60% funds).
In conclusion, the above findings clearly show the
dramatic influence of electronic factors on the selectiv-
ity of the hydroformylation reactions of vinylpyridines,
depending both on the different position of the double
bond with respect to the annular nitrogen atom and on
the electronic properties of the catalytic system.
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