Solvent- and catalyst-free regioselective hydrophosphanation of alkenes

Article abstract of DOI:10.1039/c2gc35898k

The hydrophosphanation of alkenes, an atom-economy process typically promoted by radicals or metal species, has been shown to take place in the absence of a catalyst, under solvent-free conditions and in a regioselective manner.

Full text of DOI:10.1039/c2gc35898k

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Solvent- and catalyst-free regioselective hydrophosphanation of alkenes†
Francisco Alonso,*a Yanina Moglie,a Gabriel Radivoyb and Miguel Yusa
Received 13th June 2012, Accepted 10th August 2012
DOI: 10.1039/c2gc35898k
group of Beletskaya reported the first intermolecular hydrophos-
phanation of styrenes catalysed by nickel and palladium com-
plexes.12 The process was high yielding though suffered from
some lack of atom economy under rather harsh reaction con-
ditions, involving 5 mol% Ni[P(OEt)3]4, 2 equiv. of styrene,
1 equiv. of Et3N, in benzene at 130 °C for 20 h. Some years
later, Barret et al. introduced a β-diketoimidato-stabilised
calcium amide which effectively catalysed the addition of diphe-
nylphosphane to styrene, isoprene, and 1,3-cyclohexadiene in
C6D6 (25–75 °C, 16–36 h).13 Chiral organopalladium(II) com-
plexes, prepared by Leung et al., allowed the asymmetric hydro-
phosphanation of vinyl phosphanes, aromatic enones,
functionalised allenes and alkylidene malonate esters.14
Recently, Corma et al. presented the first hydrophosphanation of
styrenes catalysed by a metal salt: (CuOTf)2·toluene (10 mol%)
in 1,4-dioxane-d8 at 100 °C for 18–24 h.15 Other diverse metal
salts, preferably FeCl2 and FeCl3, have been also shown to
promote the addition of secondary phosphanes to alkenes.16 The
formation of the anti-Markovnikov products is a common feature
for all these metal-catalysed strategies.17
Notwithstanding the utility of the aforementioned methods,
expensive and, in some cases, toxic catalytic systems are applied
often under harsh conditions. The oxidation of the resulting
phosphane to the corresponding phosphane oxide is another
inconvenience commonly encountered, which can be enhanced
by the presence of the metal. The use of neutral conditions is
also desirable in order to minimise side-reactions (e.g. poly-
merisation, self-condensation) and avoid the aqueous work-up,
which increases the risk of oxidation. In this sense, Gaumont
et al. designed an elegant approach to the unique uncatalysed
hydrophosphanation of inactivated alkenes (styrenes excluded),
starting from secondary phosphane–borane complexes.18 The
addition occurred in toluene under neutral conditions and either
classical or microwave heating (50–80 °C).
The hydrophosphanation of alkenes, an atom-economy
process typically promoted by radicals or metal species, has
been shown to take place in the absence of a catalyst, under
solvent-free conditions and in a regioselective manner.
Organophosphorus compounds are widely used in the chemical,
agrochemical, and pharmaceutical industries.1 In particular,
phosphane ligands are of paramount importance in organic syn-
thesis, especially in homogeneous and asymmetric catalysis.2 In
recent years, increasing attention has also been devoted to the
design of metal–phosphane complexes with anticancer activity,
as potential substitutes of the current platinum drugs.3 The tra-
ditional methods for the synthesis of phosphanes include (a) the
reaction of an organometallic reagent with a phosphorus halide
or a phosphane bearing a good leaving group, (b) reaction of a
metal phosphide with an organic electrophile, (c) reduction of a
phosphorus halide or oxide, and (d) from elemental phosphorus.4
The direct addition of the P–H bond to alkenes is, however, a
more suitable approach from the green chemistry and atom
economy point of view since no by-products are formed. This
reaction, known as hydrophosphanation,5 has been much less
studied than the hydrophosphinylation6 and hydrophosphoryla-
tion7 counterparts.
The hydrophosphanation of alkenes was initially conducted
under base catalysis or radical activation, leading to the anti-
Markovnikov products.5c In contrast, the acid-promoted reaction
was barely documented and led to the Markovnikov products.8
A new era for the addition of phosphanes to alkenes began with
the advent of the transition-metal catalysed methodologies.5 Pio-
neering work in the late nineties was developed by Glueck et al.
on the platinum-catalyzed anti-Markovnikov hydrophosphana-
tion of the activated alkene acrylonitrile.9 In the early 21st
century, the group of Marks described the utility of lanthano-
cenes as catalysts for the intramolecular hydrophosphanation of
primary and secondary alkenyl phosphanes.10 Soon after, the
ytterbium-catalysed addition of diphenylphosphane to isoprene
and two styrenes was reported by Takaki et al.11 In 2002, the
Our interest in the transition-metal catalysed addition of Het–
H bonds across carbon–carbon multiple bonds19 led us to the
discovery of the uncatalysed addition of secondary phosphanes
to alkenes under solvent-free conditions. We initially studied the
solvent effect on the addition of diphenylphosphane to styrene as
a model reaction. The experiments were conducted in common
organic solvents at 70 °C, under an argon atmosphere in order to
prevent the in situ oxidation of the reagent diphenylphosphane to
the corresponding phosphane oxide. Among them, CH2Cl2,
MeCN, and EtOH were found to be very inappropriate solvents
(Table 1, entries 1, 6, and 7, respectively), whereas marginal-to-
low conversions into the product were obtained in THF, toluene,
DMSO or DMF (Table 1, entries 2–5). In contrast, quantitative
aDepartamento de Química Orgánica, Facultad de Ciencias and
Instituto de Síntesis Orgánica (ISO), Universidad de Alicante, Apdo 99,
03080 Alicante, Spain. E-mail: falonso@ua.es; Fax: (+34)965903549;
Tel: (+34)965903548
bDepartamento de Química, Instituto de Química del Sur
(INQUISUR-CONICET), Universidad Nacional del Sur, Avenida Alem
1253, 8000 Bahía Blanca, Argentina
†Electronic supplementary information (ESI) available: General
remarks, experimental procedure, physical and spectroscopic data of
new compounds, and NMR spectra. See DOI: 10.1039/c2gc35898k
This journal is © The Royal Society of Chemistry 2012
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Table 1 Uncatalysed addition of diphenylphosphane to styrene in
Table 2 Solvent- and catalyst-free hydrophosphanation of alkenesa
different solventsa
Entry
Solvent
Conversionb (%)
1
2
3
4
5
6
7
8
CH2Cl2
THF
PhMe
DMSO
DMF
MeCN
EtOH
None
0
2
13
7
19
0
0
>99
a Reaction conditions: 1a (0.5 mmol), diphenylphosphane (0.5 mmol),
solvent (1 mL), 70 °C, 24 h, Ar atmosphere. b Determined by GLC.
conversion was recorded for the reaction carried out in the
absence of a solvent (Table 1, entry 8). Solvent-free organic syn-
thesis is one of the most promising steps toward waste preven-
tion and environmental protection.20
We next extended this uncatalysed solvent-free protocol to a
variety of alkenes.‡ All reactions were performed with new mag-
netic bars in order to rule out any catalysis by traces of metals.
Among the styrenes tested, styrene (product 2a) was found to
react faster than the p-halostyrenes (products 2b and 2c), albeit
similar good yields were reached in all cases. The process was
also high yielding for p-methoxy- and p-acetoxystyrene (2d and
2e, respectively). The hydrophosphanation of vinyl pyridines
furnished the expected heterocyclic products 2f and 2g; the
former is a P,N-bidentate ligand known as pyphos, which has
found application in homogeneous transition-metal catalysis.21
Yields around 90% were recorded in the hydrophosphanation of
either 2-vinylnaphthalene or 4-vinyl-1,1′-biphenyl (2h and 2i,
respectively). Interestingly, the much less reactive gem-disubsti-
tuted alkene isopropenyl benzene successfully reacted under the
standard conditions, giving rise to 2j in 79% yield. Moreover,
diphenylphosphane could be also added to N-vinyl compounds,
such as N-vinylphthalimide or N-vinylpyrrolidin-2-one, though
longer time was needed in order to attain good yields (2k and 2l,
respectively). A P,S-bidentate ligand (2m), also applied in cataly-
sis,22 was nicely prepared from phenyl vinyl sulphide. In con-
trast, vinyl ethers were rather reluctant to react under the
standard conditions. We next studied the hydrophosphanation of
some activated alkenes such as methyl vinyl ketone, ethyl acry-
late, and acrylonitrile. We were delighted to observe that reac-
tions proceeded at room temperature (7 h) with similar yields as
at 70 °C, though were faster by heating (1–3 h). 4-(Diphenylphos-
phanyl)butan-2-one (2n) was obtained in lower yield due to
some by-product formation involving two molecules of the sub-
strate. This side reaction was not observed in the case of 2o. It is
noteworthy that the addition of diphenylphosphane to acrylo-
nitrile, a reaction deeply studied under platinum catalysis,9 was
effectively accomplished in the absence of a catalyst, even at
room temperature (2p).
a Reaction conditions: 1 (0.5 mmol), diphenylphosphane (0.5 mmol),
70 °C or rt, Ar atmosphere; reaction time and isolated yield in
parentheses.
compounds 2c and 2i–2l. Minor amounts of the corresponding
phosphane oxides (10–15%) were detected in some cases as a
result of the addition of partially oxidised diphenylphosphane
and/or spontaneous oxidation of the product 2. Nevertheless,
We must remark that conversions in the range 96–>99% were
generally achieved except for the alkene precursors of
2700 | Green Chem., 2012, 14, 2699–2702
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Table 3 Addition of diphenylphosphane to styrene
reactions. Further studies on the substrate scope of this simple
methodology are under way.
Acknowledgements
T
Time
Yielda
(%)
This work was generously supported by the Spanish Ministerio
de Ciencia e Innovación (MICINN; CTQ2007-65218 and Con-
solider Ingenio 2010-CSD2007-00006), the Generalitat Valenci-
ana (GV; PROMETEO/2009/039), and Fondo Europeo de
Desarrollo Regional (FEDER). Y. M. acknowledges the Instituto
de Síntesis Orgánica (ISO) of the Universidad de Alicante for a
grant.
Entry Catalyst (mol%)
Solvent
(°C) (h)
123
212a
313a
415
516
6e
t-BuOK (20)
Ni[P(OEt)3]4 (5)
Ca complex (10)
(CuOTf)2·PhMe (10) Dioxane-d8 100
FeCl2 (30)
None
DMSO
C6H6
C6D6
rt
130
75
1
83
20
20
>99b
95c
18–24 92b
MeCN
None
60
70
12
4
97d
82
a Isolated yield unless otherwise stated. b 31P NMR yield. c Conversion
by NMR. d Isolated as the borane complex. e This communication.
Notes and references
‡General procedure: Diphenylphosphane (0.5 mmol, 87 μL) and the
alkene (0.5 mmol) were stirred under argon during the specified time at
70 °C or room temperature (see Table 2). The progress of the reaction
was monitored by TLC and GLC until total or steady conversion was
achieved. The resulting mixture was subjected to column chromato-
graphy (silica gel, hexane–EtOAc) to give the pure phosphanes 2.
1 L. D. Quin, A Guide to Organophosphorus Chemistry, Wiley-Inter-
science, New York, 2000.
Scheme 1 Uncatalysed solvent-free addition of diphenylphosphane to
2 For recent reviews and monographs, see: (a) Phosphorus Ligands
in Asymmetric Catalysis: Synthesis and Applications, ed. A. Börner,
Wiley-VCH, Weinheim, 2008; (b) P. E. Goudriann, P. W. N. M. van
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phenylacetylene.
easy and quick purification by column chromatography provided
the pure tertiary phosphanes. Furthermore, all reactions were
shown to be highly regioselective, exclusively affording the anti-
Markovnikov products. Table 3 clearly shows more evidence
about how advantageous the title reaction is in the hydrophos-
phanation of styrene when compared with the reported catalytic
procedures.
We checked that the addition of radical traps, such as cumene,
TEMPO or 2,6-di-tert-butylphenol, did not inhibit the hydro-
phosphanation of styrenes (>96% conversion) and no products
derived from their reaction with diphenylphosphanyl radicals
were detected. In addition, no cyclisation product was formed by
the addition of diphenylphosphane to hepta-1,6-diene, with all
these results practically discarding any free-radical process.
Finally, we proved the potential application of this simple
methodology to the synthesis of vinyl phosphanes. As an
example, the solvent- and catalyst-free hydrophosphanation of
phenylacetylene yielded the diphenyl(styryl)phosphane 4 in a
regio- and stereoselective manner, mainly following an anti-
Markovnikov anti-addition (Scheme 1).
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Conclusions
We have demonstrated the feasibility of the uncatalysed direct
addition of phosphanes to alkenes when carried out in the
absence of a solvent. Styrenes, N- and S-vinyl compounds, as
well as activated alkenes, underwent this atom-economy addition
in moderate-to-high isolated yields (70–91%) at 70 °C or room
temperature (in the latter case). The process is highly regioselec-
tive producing all tertiary phosphanes in an anti-Markovnikov
fashion. These results emphasize how important it is to perform
control experiments in the absence of a catalyst and the crucial
role that the concentration effect can play in solvent-free
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