CHEMCATCHEM
COMMUNICATIONS
DOI: 10.1002/cctc.201301029
A Copper-Catalyzed Variant of the Michaelis–Arbuzov
Reaction
Jorge Ballester,[a] Jꢀrꢀmie Gatignol,[b] Guntram Schmidt,[a] Carole Alayrac,[b] Annie-
Claude Gaumont,*[b] and Marc Taillefer*[a]
As part of our studies on copper-catalyzed arylation of nucleo-
philes, we report on Michaelis–Arbuzov reactions with a novel
catalytic system, featuring a copper(I) salt as precatalyst with-
out any additional ligand. This procedure is an interesting al-
ternative to the use of expensive and toxic transition metals
(nickel, palladium) traditionally used as catalysts in Michaelis–
Arbuzov reactions. Our approach allows the synthesis from
triethylphosphite, diethyl aryl phosphonite, and diaryl ethyl-
phosphinite of various aryl phosphonates, aryl phosphinates,
and aryl phosphine oxides, respectively. These families of com-
pounds are essential owing to their respective importance in
bioorganic and medical chemistry, their applicability as flame
retardants, and their usability in coordination chemistry and
catalysis.
synthesis of the corresponding phosphonates and phosphi-
nates. There remained, however, large shortcomings in the
range of substrates and the alloy had to be employed stoichio-
metrically. The first catalytic Michaelis–Arbuzov reactions were
reported in 1970.[25] They allowed the conversion of further
substituted aryl and vinyl halides, but were dependent on the
usage of toxic nickel salt catalysts and high temperatures
(1608C). There were also sporadic reports on palladium cata-
lysts but these were limited to singular reactions.[26–28] Further
developments in Michaelis–Arbuzov reactions involving copper
suffered the disadvantages of dependence on stoichiometric
amounts of copper and harsh reaction conditions.[29–31]
As part of our studies on the copper-catalyzed arylation of
nucleophiles,[32] we report herein Michaelis–Arbuzov reactions
with a novel catalytic system that features a copper(I) salt as
precatalyst without any additional ligand. Our approach allows
the synthesis of various aryl phosphonates, aryl phosphinates,
and aryl phosphine oxides.[33]
The Michaelis–Arbuzov reaction, discovered by A. Michaelis in
1898[1] and explored soon thereafter by A. Arbuzov,[2–4] has
been widely used for the synthesis of various phosphonates,
phosphinates, phosphine oxides, and phosphines.[5–8] Nowa-
days, these compound families are essential owing to their im-
portance in bioorganic and medical chemistry,[9–12] their applic-
ability as flame retardants,[13–15] and their usability in coordina-
tion chemistry and catalysis,[16–19] respectively. The Michaelis–
Arbuzov protocol has been limited for a long time to reactions
between nucleophilic phosphites and electrophilic alkyl hal-
ides, resulting in the formation of the corresponding alkyl
phosphonates. Thus, the classical method did not allow con-
version of aryl halides into aryl phosphonates and derivatives,
which are valuable intermediates in organic synthesis[20,21] and
of great importance in polymer chemistry.[22,23] In 1967 Tavs
and Korte described the first Michaelis–Arbuzov reactions in-
volving a copper–tin alloy.[24] The range of possible substrates
was thus extended, enabling the use of aryl halides for the
Ligand-free copper(I) iodide was chosen as the catalyst for
the reactions and the reaction conditions were optimized by
using the model substrates iodobenzene and triethylphos-
phite. Several solvents were tested at reflux but no product
formation was observed (Table 1, entry 1) unless cesium car-
bonate was added to the system, which led to the formation
Table 1. Ligand-free copper-catalyzed Michaelis–Arbuzov reaction be-
tween phenyl iodide and triethylphosphite: parametric study.[a]
Entry Solvent (2 mL)
Base [equiv.]
Yield [%][b]
1
toluene, CH3CN, DMSO, EtOH, THF –
–
2
toluene
Cs2CO3 (1)
20
3
4
5
6
7
8
9
10
11
12
toluene
toluene
toluene
toluene
DMF
CH3CN
EtOH, THF, H2O, dioxane
toluene
toluene
Cs2CO3 (2)
Cs2CO3 (3)
Cs2CO3 (4)
Cs2CO3 (4)
Cs2CO3 (4)
Cs2CO3 (4)
Cs2CO3 (4)
CsOH (4), K2CO3 (4)
Et3N (4), pyridine (4)
K3PO4 (4)
50
73
95, 92[c]
4[d]
[a] J. Ballester, G. Schmidt, Dr. M. Taillefer
CNRS, UMR 5253, Institut Charles Gerhardt Montpellier
ENSCM, 8, rue de l’Ecole Normale, 34296 Montpellier (France)
Fax: (+33)467-144-319
40
75, 72[c]
4–16
–
[b] J. Gatignol, Dr. C. Alayrac, Prof. A.-C. Gaumont
Laboratoire de Chimie Molꢀculaire et Thio-organique
CNRS, UMR 6507, INC3M FR3038,
–
15
ENSICAEN & Universitꢀ de Caen Basse-Normandie
6 Boulevard du Marꢀchal Juin, 14050 Caen (France)
Fax: (+33)231-452-877
toluene
[a] Reaction performed with 1 equiv. of PhI, 1 equiv. of P(OEt)3, 10 mol%
of CuI (99.9999%, Alfa), and 0–4 equiv. of base in a sealed tube at reflux.
[b] GC yield determined with 1,3-dimethoxybenzene as standard. [c] Iso-
lated yield. [d] Reaction performed at 1008C.
Supporting information for this article is available on the WWW under
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 4
&
1
&
ÞÞ
These are not the final page numbers!