Stepwise hydroformylation of C,N-divinylpyrroles with Rh4(CO)12 under mild conditions: An original synthesis of N-vinylpyrrolylmonoaldehydes and of pyrrolyldialdehydes

Article abstract of DOI:10.1016/S0022-328X(99)00483-0

1,3-Divinylpyrrole and 1,2-divinylpyrrole were treated in a stainless steel autoclave with Rh₄(CO)₁₂ at 40°C and 120 atm of H₂/CO total pressure: for both substrates exclusive hydroformylation of the vinyl groups bonded to the ring carbon atom occurred, the branched unsaturated monoaldehydes 2-(1-vinylpyrrolyl)propanals being formed with a very high chemoselectivity and α-regioselectivity. At 80°C only 1,3-divinylpyrrole gives, via hydroformylation of N-vinyl group, the corresponding dialdehydes.

Full text of DOI:10.1016/S0022-328X(99)00483-0

www.elsevier.nl/locate/jorganchem
Journal of Organometallic Chemistry 592 (1999) 69–73
Stepwise hydroformylation of C,N-divinylpyrroles with Rh4(CO)12
under mild conditions: an original synthesis of
N-vinylpyrrolylmonoaldehydes and of pyrrolyldialdehydes
Raffaello Lazzaroni a,*, Roberta Settambolo b, Manuela Mariani a, Aldo Caiazzo a
a Centro di Studio CNR per le Macromolecole Stereordinate ed Otticamente Atti6e, Dipartimento di Chimica e Chimica Industriale,
6ia Risorgimento 35, 56126 Pisa, Italy
b Istituto di Chimica Quantistica ed Energetica Molecolare del CNR, Dipartimento di Chimica e Chimica Industriale, 6ia Risorgimento 35,
56126 Pisa, Italy
Received 2 June 1999; accepted 2 August 1999
Abstract
1,3-Divinylpyrrole and 1,2-divinylpyrrole were treated in a stainless steel autoclave with Rh4(CO)12 at 40°C and 120 atm of
H2/CO total pressure: for both substrates exclusive hydroformylation of the vinyl groups bonded to the ring carbon atom
occurred, the branched unsaturated monoaldehydes 2-(1-vinylpyrrolyl)propanals being formed with a very high chemoselectivity
and a-regioselectivity. At 80°C only 1,3-divinylpyrrole gives, via hydroformylation of N-vinyl group, the corresponding
dialdehydes. © 1999 Elsevier Science S.A. All rights reserved.
Keywords: Hydroformylation; Deuterioformylation; Pyrrolepropanols; Rhodium; Catalysis
matic ring as well as on the relative position of the
double bond with respect to the annular heteroatom.
1. Introduction
The above effects have been widely pointed out, by
various authors and by us, in the rhodium-catalyzed
hydroformylation of styrene [1a], substituted styrenes
[2], simple vinylpyrroles [12] and vinylpyridines [13].
In spite of the fact that the most functionalized or
unfunctionalized aromatic vinylsubstrates have been
submitted to hydroformylation, no examples involving
divinylsubstrates containing two unsaturated groups on
the same aromatic ring have been previously reported
in the literature.
Owing to our interest into the selectivity of hydro-
formylation with respect to both mechanistic and syn-
thetic points of view, we first investigated this research
field, by hydroformylating the recently synthesized 1,3-
and 1,2-divinylpyrroles (1a and 1b) [14], characterized
by a N-vinyl group and a C-vinyl group in 1–3 or 1–2
positions, respectively of the same pyrrole ring. These
substrates seemed very interesting as precursors to
pyrrolyl aldehydes as well as to providing an opportu-
nity to investigate the reactivity of a C- and a N-vinyl
group bonded to the same aromatic ring.
Reaction selectivity is a desired goal in organic syn-
thesis. Among catalytic processes, the rhodium-cata-
lyzed hydroformylation of vinyl- or vinylidenic
aromatic and heteroaromatic olefins constitutes a very
significant example [1–9]. Indeed with the former sub-
strates a high or complete selectivity in the branched
isomeric aldehydes was observed, while with the latter
introduction of the formyl group occurred only at the
terminal position of the double bond. The above find-
ings have been successfully applied in the synthesis of
various pharmaceuticals, i.e. anti-inflammatory 2-aryl-
propionic acids [10] and antiallergic agents [11].
Although the branched aldehyde is largely favored in
the hydroformylation of aromatic or heteroaromatic
vinylsubstrates, its amount can vary and depends on
the electron-poor or p-excessive character of the aro-
* Corresponding author. Tel.: +39-050-918-227; fax: +39-050-
918-260.
E-mail address: lazzaroni@dcci.unipi.it (R. Lazzaroni)
0022-328X/99/$ - see front matter © 1999 Elsevier Science S.A. All rights reserved.
PII: S0022-328X(99)00483-0

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R. Lazzaroni et al. / Journal of Organometallic Chemistry 592 (1999) 69–73
2b have been isolated by column chromatography and
1
characterized by H-NMR and MS analysis.
When the reaction mixture containing the 1-vinyl-
aldehydes isomers 2a and 3a, arising from the hydro-
formylation of 1,3-divinylpyrrole (1a) at 40°C, was
heated at 80°C, the hydroformylation of the N-vinyl
took place and the dialdehydes 4a and 5a, due to
insertion of the formyl group exclusively in the a-posi-
tion of the N-vinyl moiety, were formed (4a/5a=92/8)
(at TB80°C the process was very slow) (Scheme 2). An
analogous result was obtained when hydroformylation
at 80°C was carried out directly on 1,3-divinylpyrrole
(1a): the formation of the 1-vinylmonoaldehydes 2a and
3a (2a/3a=86/14) was observed until unconverted C-
vinyl was present in the reaction mixture. At complete
conversion of 1a, the hydroformylation of the N-vinyl
in 2a and 3a occurred, giving the dialdehyde isomers 4a
and 5a (4a/5a=86/14).
In this paper, we report that when 1a and 1b were
treated in a stainless steel autoclave with Rh4(CO)12, at
40°C and 120 atm of H2–CO total pressure, an original
and very interesting selectivity was observed: the C-
vinyl group reacted faster than the N-vinyl one in both
the substrates, the corresponding branched monoalde-
hydes 2-(1-vinylpyrrolyl)propanals 2a and 2b being
formed with very high chemoselectivity (\98%) and
a-regioselectivity (2a/3a=93/7; 2b/3b=98/2) (Scheme
1).
In contrast, hydroformylation experiments carried
out at 80°C on 1b gave the dialdehydes 4b and 5b in a
very low yield and the formation of various unidentified
by-products had occurred.
The aldehydes 3a, 3b, 4a and 5a have been character-
ized by identification of their typical signals in the
1H-NMR and mass spectra of reaction mixtures and by
a comparison with the spectra of the monoaldehydes
coming from the hydroformylation of the single
vinylpyrrole isomers [7,12].
2. Results
The hydroformylation experiments on 1a and 1b
were carried out in toluene with Rh4(CO)12 as catalytic
precursor, at 40°C and 120 atm pressure (1:1 CO–H2),
using a 100/1 substrate/rhodium ratio (Scheme 1). The
substrate conversion and the composition of the reac-
tion mixtures were analysed by GC and GC/MS, using
o-xylene as internal standard. The chemoselectivity into
the aldehydes 2 and 3, coming from exclusive function-
alization of the C-vinyl, was very high for both the
substrates (\98%) (Table 1). Only traces of the
monoaldehydes 2%a–b and 3%a–b (Scheme 1), due to the
hydroformylation of the vinyl group bonded to the
nitrogen atom (N-vinyl), were observed. The regioiso-
meric ratio 2/3 was higher for 1b (98/2) than for 1a
(93/7). The chemo- and regioselectivity kept constant
during the reaction proceeding (Table 1).
3. Discussion and conclusion
The above findings indicate that, in the adopted
experimental conditions, the C-vinyl is more reactive
than the N-vinyl and chemoselective monohydroformyl-
ation to N-vinylpyrrolylpropanals takes place. Such a
finding is in agreement with the higher reaction rate
previously observed for 2- and 3-vinylpyrrole with re-
spect to N-vinyl isomer [7,12].
In order to obtain more information about this, an
equimolecular mixture of simple 3-vinylpyrrole [15] and
N-vinylpyrrole [16] was submitted to hydroformylation
at 40°C, in the presence of Rh4(CO)12 as catalyst pre-
cursor. We found that the former substrate was hydro-
formylated first, whereas the latter reacted more slowly
The double bond involved in the functionalization
was easily identified by looking at the disappearance of
the well-resolved signals of the protons of the C-vinyl
groups [14] in the H-NMR spectra of hydroformyla-
tion mixtures. The newly synthesized aldehydes 2a and
1
Scheme 1.

R. Lazzaroni et al. / Journal of Organometallic Chemistry 592 (1999) 69–73
71
Table 1
Hydroformylation of 1,3-divinylpyrrole (1a) and 1,2-divinylpyrrole (1b) with Rh4(CO)12 as catalytic precursor, at 40°C a
Substrate
Reaction time (h)
2
15
1
3.5
Conversion (%)
[(2+3)/(2+3+2%+3%)] b (%)
100
98
99
98
(2/3) c (%)
93/7
93/7
98/2
98/2
[(2%+3%)/(2%+3%+2+3)] b (%)
1a
1a
1b
1b
44
94
57
90
–
2
1
2
a A 5 ml toluene solution containing 4 mmol of substrate; substrate/Rh=100/1; 1:1 CO–H2; 120 atm pressure; volume of the reactor vessel 25
ml. The mixture composition was determined via GLC using o-xylene as internal standard; 91% accuracy.
b Chemoselectivity.
c Regioselectivity.
(rate ratio 16:1). The regioselectivity observed for 3-
vinylpyrrole (a/b=92/8) in the mixture was very simi-
lar to that obtained in the hydroformylation of
3-vinylpyrrole alone [7,12] and also of the C-vinyl in
1,3-divinylpyrrole under the same experimental condi-
tions. A similar behavior has also been observed at
higher temperatures. In fact the regioisomeric ratio
2a/3a=88/12 found in the hydroformylation of the
C-vinyl group of 1a at 80°C is in agreement with the
depression of a-regioselectivity with increasing tempera-
ture which was observed in the hydroformylation of the
corresponding simple 3-vinylpyrrole [12]. The compari-
son of the results obtained in the case of 3-vinylpyrrole
together with the data relative to the hydroformylation
of the C-vinyl in 1,3-divinylpyrrole seems to exclude a
significant influence of the N-vinyl on the chemo- and
regioselectivity when the two double bonds are on the
same heteroaromatic ring. Confirmation of this comes
from semiempirical calculations (CNDO) [13,17] car-
ried out on divinyl- and monovinylpyrroles, which
showed the two double bonds in the disubstituted struc-
ture. The same charge distribution was observed for the
same type of vinyl group in simple monovinylpyrroles.
The minor hydroformylation rate observed for N-vinyl
could be due to the minor charge density in this double
bond with respect to the charge density in C-vinyl. This
factor could make the C-vinyl group more available
than the N-vinyl one for the insertion into RhꢀH bond
during the catalytic cycle [3,12], the effect being equally
active in the mono- as in the divinylpyrroles.
appears does hydroformylation of styrene take place.
In conclusion, the rhodium-catalyzed hydroformyla-
tion of the divinylpyrroles 1a and 1b to 1-vinylpyrrolyl-
monoaldehydes reported here is an original example of
a chemoselective and twice regioselective reaction: in
fact the insertion of the formyl group selectively occurs
on Ca carbon atom of the C-vinyl group.
As 2-pyrrolylpropanals are precursors of biologically
active compounds [19], the N-vinyl pyrrolylaldehydes
obtained could constitute versatile intermediates in the
synthesis of fine chemicals.
It is interesting that the dialdehydes coming from the
high-temperature hydroformylation of N-vinylpyrrolyl-
dialdehydes constitute the first example of 1,7- and
1,8-dialdehydes carrying out a pyrrole ring in the mid-
dle of the carbon atom chain. Actually dialdehydes of
this type are the subject of considerable interest as
cross-linking agents in the biochemistry of proteins as
well as new tanning agents. They represent an alterna-
tive to the traditional chromium-based ones [20].
In the light of the above findings, hydroformylation
in the presence of rhodium-based catalyst precursors is
likely to be an increasingly useful synthetic method,
because of its tolerance to a variety of functional
groups [21–24]. In order to expand this potential, we
are now carrying out studies on the rhodium-catalyzed
hydroformylation of vinyl- and allylpyrroles bearing
other groups on the heteroaromatic ring.
The lower hydroformylation rate observed for N-
vinylpyrrole with respect to the C-vinyl one, pre-
dictable, in principle, on the basis of the results
obtained in the hydroformylation of the mono
vinylpyrrole isomers [7,12], is not an obvious result if
we take into account the behavior of styrene and 2- or
4-vinylpyridine [18] under hydroformylation condition.
When the above substrates are hydroformylated sepa-
rately, styrene reacts faster than vinylpyridines. In con-
trast, for a mixture of styrene and vinylpyridine, the
reaction rate of vinylpyridine is much higher than that
of styrene. In practice, vinylpyridine prevents the
styrene reactivity and only when the vinylpyridine dis-
4. Experimental
All reagents were of commercial quality. Silica gel
(70–230 mesh) was purchased from Merck.
Toluene was dried over molecular sieves and distilled
under nitrogen. Microanalyses were performed at Lab-
oratorio di Microanalisi, Istituto di Chimica Organica,
Facolta` di Farmacia, Universita` di Pisa. 1H-NMR spec-
tra (200 MHz) were recorded in CDCl3. 1-vinylpyrrole
[16], 3-vinylpyrrole [15], 1,3-divinylpyrrole (1a) [14] and
1,2-divinylpyrrole (1b) [14] were synthesized as de-
scribed in the literature. Rh4(CO)12 was prepared ac-
cording to a well-known procedure [25,26].

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R. Lazzaroni et al. / Journal of Organometallic Chemistry 592 (1999) 69–73
Scheme 2.
4.1. Hydroformylation of 6inyl and di6inylpyrroles
4.1.1. General procedure
4.1.1.5. 1,3-bis(1-formylethyl)pyrrole (4a). 1H-NMR l
9.57 (d, 1H), 6.68 (m, 1H), 6.57 (m, 1H), 6.14 (m, 1H),
4.52 (q, 1H), 3.53–3.40 (m, 1H), 1.60 (d, 3H, J=7.3
Hz), 1.37 (d, 3H, J=7.3 Hz); MS m/e 179 (M+, 26.5),
150 (95.3), 122 (100), 106 (17), 93 (17), 77 (20.3).
4.1.1.1. 2-(1-Vinylpyrrol-3-yl)propanal (2a). A solution
of 1,3-divinylpyrrole (1a) (4.2×10−3 mol) and
Rh4(CO)12 (21 mg, 2.8×10−5 mol) in toluene (5 ml)
was introduced by suction into an evacuated 25 ml
stainless steel reaction vessel. Carbon monoxide was
introduced, the autoclave was then rocked and heated
to 40°C and hydrogen was rapidly introduced to the
desired total pressure (120 atm; 1:1 CO–H2). After 3 h
at 40°C the reaction was completed and regioisomeric
ratio 1a/1b was 92/8. From the reaction mixture 2-(1-
vinylpyrrol-3-yl)propanal (2a) was obtained as an oily
residue, by column chromatography on silica gel, by
4.1.1.6. 1-(1-Formylethyl)-3-(2-formylethyl)pyrrole (4b).
1H-NMR typical signals l 9.81 (t, 2H), 2.95–2.70 (m,
4H); MS m/e 179 (M+, 32.8), 150 (75), 122 (48.4), 106
(100), 94 (54.6), 79 (23.4).
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.
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(4.8), 120 (100), 105 (27.7), 93 (13.8), 80 (12.5). Anal.
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m/e 149 (M+, 72.2), 120 (33.3), 106 (100), 93 (70.8), 79
(50.7), 65 (18).

R. Lazzaroni et al. / Journal of Organometallic Chemistry 592 (1999) 69–73
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