Phosphine-catalyzed dimerization of activated alkenes under ambient and high pressure conditions

Article abstract of DOI:10.1016/S0040-4039(00)00346-4

Acrylic compounds dimerize under Morita-Baylis-Hillman conditions in the presence of soluble phosphines. Dimerization of β-substituted analogs may require high pressures. The process is selective and high yielding and affords densely functionalized products. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00346-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3091–3094
Phosphine-catalyzed dimerization of activated alkenes under
ambient and high pressure conditions
∗
Gérard Jenner
Laboratoire de Piézochimie Organique (UMR 7509), Faculté de Chimie, Université Louis Pasteur, 67008 Strasbourg, France
Received 17 February 2000; accepted 22 February 2000
Abstract
Acrylic compounds dimerize under Morita–Baylis–Hillman conditions in the presence of soluble phosphines.
Dimerization of β-substituted analogs may require high pressures. The process is selective and high yielding and
affords densely functionalized products. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: dimerization; Morita–Baylis–Hillman reaction; acrylic compounds; phosphines; pressure.
Morita–Baylis–Hillman (MBH) reactions are currently and intensively reactivated in view of their
1
considerable synthetic interest. The poor yields obtained until these last years are now susceptible to
be remarkably increased with the help of new methods: e.g. high pressure2,3 or catalysis. Unhindered
4
acrylic compounds add to benzaldehyde under MBH conditions, affording excellent yields of functiona-
4
lized acrylic derivatives. However, if the access to β-reaction centers is hindered, the reaction becomes
exceedingly sluggish. As an illustrative example, crotononitrile reacts with benzaldehyde only under
5
pressures in excess of 1200 MPa. Phosphines were originally the catalysts in the MBH addition of
6
aldehydes to acrylonitrile. Later, they were replaced by cyclic tertiary amines, mostly DABCO. In the
7–9
last few years, phosphines emerged again and were used sporadically. Amri et al. could dimerize in
7
this way unhindered acrylates. However, with this exception, acrylic compounds did not undergo MBH
dimerization, especially hindered derivatives, due to the reduced steric accessibility of the β-position in
the acrylic compound.
While we were studying nucleophilic addition reactions involving crotononitrile under high pressure,
we observed in the slowest reactions a by-product of the expected addition product. It was shown to be a
dimer of the acrylic nitrile. The catalyst employed in the reaction was tri-n-butylphosphine. Clearly, the
reaction afforded dimer 1 formed according to a typical MBH reaction (Eq. (1)). These results prompted
us to investigate in more detail the MBH dimerization process of activated alkenes.10 In the first step,
we screened the catalytic ability of several phosphines and cyclic tertiary amines in the dimerization
∗
Tel./fax: (33)03 88 41 68 15; e-mail: jenner@chimie.u-strasbg.fr (G. Jenner)
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00346-4
tetl 16626

3
092
of crotononitrile, a hindered acrylic nitrile (Table 1) with comparison to the traditional MBH catalysts
DABCO, 3-quinuclidinol).
(
(1)
Table 1
, R =H, X=CN) (bulk, 50°C, 24 h, catalyst-5% molar)
MBH dimerization of crotononitrile (R
1
=CH
3
2
The tertiary amines commonly used for the MBH reaction (DABCO, quinuclidinol) were completely
inactive even at 300 MPa. In a former study, it was found that DABCO (10%) was able to catalyze
3
the dimerization of acrylonitrile and methyl acrylate at 300 MPa. The interesting point in Table 1 is
that phosphines and complex cyclic amines can be efficient. The best was trisdimethylaminophosphine
which converted the monomer into the dimer to 87%. Tri-n-butylphosphine, DBU and DBN catalyzed
the MBH reaction, however it was less efficient. The modest yields obtained in the presence of these
catalysts were remarkably increased under pressure, particularly with P(nC H ) affording a quantitative
4
9 3
2,3
yield of 1. The result is in agreement with the general pressure effect in MBH reactions. The solid
phosphines P(C H ) and P(C H ) did not catalyze the dimerization reaction.
6
11 3
6
5 3
The effect of pressure on the DABCO-catalyzed cis:trans isomerization of crotononitrile was investi-
gated previously. It was found that under neat conditions the formation of the trans isomer increased with
5
increasing pressure. In fact, we observed a higher trans concentration in the dimer mixture. This seems
mainly due to the phosphine (a slight pressure effect may also be taken into account) since DBN and
DBU did not change the isomer ratio of 1 if compared to the cis:trans ratio of the starting crotononitrile.

3
093
In the next step we extended the study to the MBH dimerization of acrylic nitriles, esters, ketones
Table 2).
(
(
i) Acrylonitrile dimerized spontaneously at ambient pressure using P(C H ) as catalyst (entry 1). In
4 9 3
a former study it was found that DABCO was also able to catalyze the dimerization of this nitrile,
3
however, only under 300 MPa. cis-2-Pentenenitrile could be dimerized to 2 in nearly quantitative
yield at 300 MPa (entries 3 and 4) whereas cinnamonitrile was unreactive even at very high pressures
(900 MPa) (entry 5).
Table 2
Phosphine-catalyzed dimerization of activated alkenes (bulk, 50°C, 24 h) (Eq. (1))
(
ii) Methyl acrylate was converted to 2-methylene glutaric methyl ester with P(C H ) at ambient
4 9 3
1
1
3
pressure (entry 6) (51% yield with DABCO at 300 MPa ). Crotonates, however, did not react
under normal conditions. Dimerization of methyl and ethyl crotonate occurred under 300 MPa with
P[N(CH ) ] as catalyst (entries 8–10). Other phosphines as well as DBU and DBN were unable to
3
2
catalyze the reaction. The highly crowded methyl 3,3-dimethyl acrylate was practically unreactive
even under elevated pressure (entry 12) affording only a trace of the supposed dimer.
(iii) The enone examined dimerized easily at 0.1 MPa with phosphine catalysts (entry 12). The dimer
5
was previously obtained in 85% yield in the presence of DBU at 185°C in imidazolinedione as
1
2
solvent.
In summary, activated alkenes can undergo dimerization under MBH conditions in the presence
of peculiar trialkylphosphines.1 Whereas unhindered compounds dimerize in high yields at ambient
pressure, substituted acrylic compounds generally require high pressures (300 MPa and above). The
process affords selectively densely functionalized ethylenic derivatives.
3

3
094
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9
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1
0. A PTFE tube was filled up with hydroquinone (polymerization inhibitor), standard (trimethoxybenzene or bibenzyl
according to run), phosphine and completed with the acrylic compound. After reaction the content was poured into a 4N
1
HCl solution to remove the phosphine. Usual work-up yielded the residue which was directly analyzed by H NMR (CDCl
3
,
2
00 MHz, δ ppm): 1 trans: 6.48 (q, 1H, CH-C), 2.69 (m, 1H, CH-C_C), 2.44 (d, 2H, CH
CH ); 1 cis: 6.55 (q, 1H, CH-C), 3.12 (m, 1H, CH-C_C), 2.51 (d, 2H, CH ), 1.97 (d, 3H, CH
t, 1H, CH_C), 2.81 (m, 1H, CH-C_C), 2.35–2.46 (br, 4H, CH ), 1.56 (br, 2H, CH
: 6.74 (q, 1H, CH_C), 3.63 (s, 3H, OCH ), 3.54 (s, 3H, OCH ), 3.26 (m, 1H, CH-C_C), 2.44–2.72 (dd, 2H, CH
d, 3H, CH ), 1.14 (d, 3H, CH ); 4: 6.74 (q, 1H, CH_C), 4.16 (t, 4H, OCH ), 3.32 (m, 1H, CH-C_C), 2.50–2.78 (dd, 2H,
), 1.76 (d, 3H, CH ), 1.18 (br, 6H, CH ).
2
), 1.96 (d, 3H, CH
3
), 1.24 (d, 3H,
3
2
3
), 1.33 (d, 3H, CH
3
); 2: 6.31
);
), 1.78
(
3
(
2
2 3 3
), 1.04 (m, 3H, CH ), 0.90 (t, 3H, CH
3
3
2
3
3
2
CH
2
3
3
1
1. 2-Methylene glutaro-nitrile and methyl ester could be synthesized via transition metal catalyzed dimerization of acrylonitrile
and methyl acrylate, respectively. However, the reactions were not selective (other dimers were also produced) and needed
prolonged reaction times. Crotonic derivatives did not react under such conditions. Watanabe, Y.; Takeda, M. Bull. Chem.
Soc. Jpn. 1973, 46, 883–887.
1
1
2. Hwu, J. R.; Hakimelahi, G. H.; Chou, C. Y. Tetrahedron Lett. 1992, 33, 6469–6472.
3. In contrast with the excellent yields reported in the DBU catalyzed MBH reaction (Ref. 4), the phosphines used in the
present work did not catalyze the MBH addition of benzaldehyde to acrylic compounds.