Et3B-induced radical addition of diphenylphosphine oxide to unsaturated compounds

Article abstract of DOI:10.1016/S0040-4039(03)01467-9

Et₃B-catalysed addition of diphenylphosphine oxide to unsaturated compounds, alkenes, unsaturated acids, allylic alcohols, and allylic α-O-acetyl nitriles constitutes a practical route to a variety of functionalized diphenylphosphine oxides. Th

Full text of DOI:10.1016/S0040-4039(03)01467-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6169–6171
Et3B-induced radical addition of diphenylphosphine oxide to
unsaturated compounds
Patrick Rey,a Jacques Taillades,b,* Jean Christophe Rossia and Georges Grosa
aAdisseo, 42 Avenue Aristide Briand BP100, 92164 Antony Cedex, France
bOrganisation Mole´culaire, Evolution et Mate´riaux Fluore´s (UPRES-A CNRS 5073) CC 009/CC017, Place Euge`ne Bataillon,
34095 Montpellier Cedex 5, France
Received 28 March 2003; accepted 31 March 2003
Abstract—Et3B-catalysed addition of diphenylphosphine oxide to unsaturated compounds, alkenes, unsaturated acids, allylic
alcohols, and allylic a-O-acetyl nitriles constitutes a practical route to a variety of functionalized diphenylphosphine oxides. The
very mild conditions employed, together with the short reaction times, make the procedure highly versatile and tolerant to a range
of functionalities.
© 2003 Published by Elsevier Ltd.
The Pudovik reaction is one of the most versatile
pathways for the formation of carbonꢀphosphorus
bonds (Scheme 1) and involves the addition of com-
pounds containing a labile P–H bond with unsaturated
systems (alkenes, alkynes, carbonyls, imines).1–4
Markovnikov. Indeed, when the unsaturated substrate
used has a nucleophilic character, the mechanism is
preferentially radical. In this case, photoactivation11 or
chemical initiation12 (peroxides, AIBN) is the most
efficient method. A major problem of such methods is
that the reaction time is long and the reaction condi-
tions are usually drastic.13 Furthermore, the regioselec-
tivity of the addition is sometimes weak. More recently,
ultrasound-induced radical reaction in homogeneous
medium has also been used.14 In the presence of free
radical initiators or under photochemical or ultrasound
irradiation in a homogeneous medium, the phosphory-
lated reagents (R2P(O)H) add to a double bond by a
free radical mechanism, the orientation of which is also
anti-Markovnikov.
The products of the reaction find significant applica-
tions in a wide range of areas (industrial, biological,
and chemical synthetic uses).5 The Pudovik reaction
can progress via an ionic or (and) a radical mechanism.
It appears in the literature that the difference of the
Pudovik reaction mechanisms depends on the nature of
the unsaturated substrates (activated or not). In fact,
when the unsaturated compound contains an electron-
withdrawing substituent, the main mechanism is ionic.
Diethylamine or potassium hydroxide6–9 are generally
used and recently tetramethylguanidine-catalysis has
been also employed efficiently under very mild condi-
tions.10 In a basic medium, the addition occurs by
nucleophilic attack of phosphorus anions to olefins by a
Michael-type mechanism and the orientation is anti-
In this letter we report our preliminary results concern-
ing the Et3B-induced radical addition of diphenylphos-
phine oxide to a variety of unsaturated compounds
including alkenes, unsaturated acids, allylic alcohols, as
well as an allylic a-O-acetyl nitrile (Scheme 2). We have
Scheme 1.
* Corresponding author. Tel.: (33)467143544; e-mail: jtaillad@crit.univ-montp2.fr
0040-4039/$ - see front matter © 2003 Published by Elsevier Ltd.
doi:10.1016/S0040-4039(03)01467-9

6170
P. Rey et al. / Tetrahedron Letters 44 (2003) 6169–6171
Scheme 2.
previously reported the use of Et3B to perform the
addition of alkanethiols to unsaturated systems, offer-
ing significant advantages especially in terms of experi-
mental simplicity, mild conditions and easy
work-up.15,16
Table 1). In all cases, good yields were obtained. With
other procedures, the reaction proceeds under harsh
conditions12,13 and side reactions were observed. As a
general rule, an excess of the diphenylphosphine oxide
or unsaturated compounds may be used. Indeed, in
these cases, stoichiometric amounts are necessary. We
also investigated the influence of the nature of the
solvent on the rate of addition of diphenylphosphine
oxide and the purity and the yield of the reaction. The
nature of the solvent has a prominent effect on the
course of the reaction. Actually, when the reaction of
diphenylphosphine oxide with unsaturated compounds
is carried out in methanol, the yields and the purities of
the addition products are better than in hexane and
acetone. It is quite obvious that high reaction tempera-
tures (>50°C) during a long reaction time are not
favorable for the achievement of high chemical yields.
This result is due to the formation of the dimer:
The addition takes place smoothly (20°C, MeOH) giv-
ing rise to the corresponding diphenyl alkylphosphine
oxide in good yield (Table 1) on slow addition of
catalytic amounts of the triethylborane solution (0.3
mmol) (Aldrich, 1 M in hexane) to the diphenylphos-
phine oxide (0.5 g; 2.5 mmol) and unsaturated com-
pound (2.5 mmol) in methanol (6 mL).
The regioselective monoaddition reaction can be
applied to all unsaturated bifunctionals compounds
examined simply through slight modifications of the
reaction conditions (see times and temperatures in
Table 1. Synthesis of alkyl diphenylphosphine oxide by Et3B-catalysed addition of diphenylphosphine oxide to unsaturated
compoundsa
Unsaturated compounds
Reaction time (h)/and temp. (°C)
Product
Yield (%)
1
2
3
4
5
6
7
8
9
2.5/20
2.5/20
3.5/20
3/20
3.5/20
4/20
2/10
2/20
1.5/10
Ph2P(O)CH2CH2(CH2)5CH3
Ph2P(O)CH2CH2(CH2)9CH3
Ph2P(O)CH2CH2CH2CO2H
Ph2P(O)CH2CH2CH(CH3)OH
Ph2P(O)CH2CH2C(CH3)2OH
Ph2P(O)CH2CH(CH3)CH2OH
Ph2P(O)CH2CH2CH2CN
96
95
74
80
94
79
72
85
65
Ph2P(O)CH2CH2CH(OH)CH2OH
Ph2P(O)CH2CH2CH(OAc)CN
a Purified compounds.

P. Rey et al. / Tetrahedron Letters 44 (2003) 6169–6171
6171
Ph2(O)P-P(O)Ph2. Having demonstrated that Et3B can
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In conclusion, the synthesis of the diphenyl alkylphos-
phine oxide is realized in good yields by one step via a
radical addition of diphenylphosphine oxide to unsatu-
rated compounds initiated by catalytic amounts of
molar solution of Et3B. The solvent and the tempera-
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solvents or reagents and inert atmosphere conditions
are not required).15,16
We are currently investigating the Et3B-catalysed addi-
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We wish to thank Adisseo and the Centre National de
la Recherche Scientifique (CNRS) for financial support
of this work.