Synthesis of new triphenylphosphines with pending ethynyl substituents

Article abstract of DOI:10.1016/j.tetlet.2010.05.055

The straightforward isolation and characterization of new triphenylphosphines possessing a pendent ethynyl substituent on one or several peripheral aryl ring(s) are reported. The synthesis of this family of compounds is achieved by retro-Favorsky reactions from the corresponding propargylic alcohol derivatives, themselves obtained following a classic Sonogashira-type coupling between the ad hoc bromophenyl phosphines and 2-methylbut-3-yn-2-ol.

Full text of DOI:10.1016/j.tetlet.2010.05.055

Tetrahedron Letters 51 (2010) 3786–3788
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Synthesis of new triphenylphosphines with pending ethynyl substituents
*
Guillaume Grelaud, Gilles Argouarch, Frédéric Paul
UMR CNRS 6226 Sciences Chimiques de Rennes, Université de Rennes 1, Campus de Beaulieu, 35042 Rennes Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The straightforward isolation and characterization of new triphenylphosphines possessing a pendent
ethynyl substituent on one or several peripheral aryl ring(s) are reported. The synthesis of this family
of compounds is achieved by retro-Favorsky reactions from the corresponding propargylic alcohol deriv-
atives, themselves obtained following a classic Sonogashira-type coupling between the ad hoc bromophe-
nyl phosphines and 2-methylbut-3-yn-2-ol.
Received 13 April 2010
Revised 11 May 2010
Accepted 12 May 2010
Available online 20 May 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Functional triphenylphosphines
Ethynyl derivatives
Propargylic alcohol
Retro-Favorsky
Over the last fifty years, the constant research for improving the
yields of various catalytic transformations has fostered the search
of more and more sophisticated ligands and led to the develop-
ment of a great number of new phosphines, among which are a
large number of variously functionalized triarylphosphines.1 How-
ever, in spite of these impressive synthetic achievements, only a
handful of reports was concerned with the synthesis of ethynylat-
ed triarylphosphines.2–4 In our mind, these ligands deserve a par-
ticular interest which largely exceeds the field of catalysis.2,4–6
First, the very diverse and specific reactions of the ethynyl substi-
tuent(s) allow one to undertake a wide range of organic or
inorganic structural modifications on these peculiar triarylphos-
phines.7 Then, by virtue of its unsaturated and rigid core, the
alkyne spacer permits a good electronic communication between
the phosphorus atom and any appended fragment, while control-
ling their relative spatial orientation.8 Thus, ethynylated triaryl-
phosphines such as 1–6 (Scheme 1) constitute strategic
precursors en route toward new functional ligands.
To the best of our knowledge, only 1 has been reported so far
among them (Scheme 2).2,9,10 Its synthesis has been achieved by
deprotecting the trimethylsilyl precursor 7; the latter being ob-
tained either (i) by the reaction of the diphenylphosphide anion
and ((4-bromophenyl)ethynyl)trimethylsilane (8)2 or (ii) by the
reaction of 4-(trimethylsilylethynyl)phenylate anion and chlorodi-
phenylphosphine.9 Low yields are reported for the first route, mak-
ing the second one more attractive. However, in our hands,11 using
potassium carbonate instead of PPS-supported carbonate for the
deprotection, this route proved not so effective, since large
amounts of phosphine oxide were formed each time, resulting in
overall low yields in the desired phosphine 1. This led us to develop
another general synthetic access to this known compound and its
new analogues 2–6 starting from the corresponding brominated
phosphines.
Actually, the desired alkynylated targets can be accessed by cat-
alytic cross-coupling reactions from the corresponding brominated
phosphines (Scheme 3). These precursors are available in good
yields from commercial dibromoarenes using lithium halogen ex-
change with butyl lithium, followed by electrophilic trapping with
the corresponding chlorophosphines.12–15 By this means, 4- and 3-
bromophenylene phosphine derivatives 1a–6a were isolated in one
step on a multi-gram scale. Reacting these known phosphines with
dimethylethynylcarbinol under typical Sonogashira conditions
produces the corresponding propargylic alcohol derivatives 1b–
6b in good yields after purification by column chromatography
(Table 1).16–18 In spite of the excess brominated phosphine used
as the reactant, the coupling reaction took place within days. Thus,
the excess phosphine present in the medium as the reactant or
product does not poison the active species of the transformation
by favoring the formation of coordinatively saturated species.1
An interesting feature of 1b–6b is that their very polar nature
allows an easy separation of the final compounds from the unre-
acted starting products and also from the pervasive phosphine
oxide formed as side-products during work-up of the Sonogashira
coupling reaction. These new products are obtained as yellow
gums or white solids. They were characterized by HRMS, IR, and
NMR and also by elemental analyses in several cases (see Supple-
mentary data). 31P NMR constitutes a convenient probe to check
the purity of the isolated product. As expected for these triaryl-
* Corresponding author. Tel./fax: +33 02 23 23 59 62.
E-mail address: frederic.paul@univ-rennes1.fr (F. Paul).
phosphines,
a
unique singlet between À4 and À5 ppm was
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.05.055

G. Grelaud et al. / Tetrahedron Letters 51 (2010) 3786–3788
3787
H
C
C
PPh2
H
C
C
H
C
C
PPh
P
2
3
1
2
3
H
H
H
C
C
C
C
C
C
PPh2
PPh
P
2
3
4
5
6
Scheme 1. Selected ethynylated triphenylphosphine derivatives.
LiPPh2
-78 °C,THF
MeOH
TMS
C
C
PPh2
TMS
C
C
Br
H
C
C
PPh2
2-
CO3
8
7
1
1) BuLi, - 78 °C, THF
2) ClPPh2
Scheme 2. Previously reported syntheses of 1.
detected each time, evidencing the absence of any trace of the cor-
responding phosphine oxides in the isolated products.3,5 The pres-
ence of the dimethyl propargylic substituents in 1b–6b was
confirmed by a diagnostic triple bond stretching vibration around
2100 cmÀ1 and a large mOH stretching vibration between 3200
tion. Thus, when heated in toluene in the presence of excess potas-
sium hydroxide, these compounds produced the desired
corresponding ethynyl-substituted triarylphosphines 1–6. The lat-
ter could be isolated pure as yellow oils in excellent yields after fil-
tration on silica (Table 2) and were characterized by IR and NMR.
The new phosphines 2–6 were also characterized by HRMS. The
spectroscopic signatures of 1–6 are diagnostic of their structures.
They exhibit a singlet near À4 ppm in 31P NMR for the central
phosphorus atom and the presence of the terminal triple bond is
and 3400 cmÀ1
.
3-Propargyl alcohol substituents are well known precursors of
terminal alkynes.16 Accordingly, 1b–6b could be converted into
the desired phosphines using a base-catalyzed retro-Favorsky reac-
1) BuLi, - 78 °C, THF
Br
2) ClnPPh3-n
Br
PPh3-n
Br
n
1a 6a
-
HO
PdCl2(PPh3)2 (4%)
/ CuI (8%)
C
CH
DMF / HN(iPr)2
80°C / 48 to 96 h
HO
PPh3-n
n
PPh3-n
KOH
C
C
H
C
C
toluene, Δ
n
1b-6b
1-6
(n = 1-3; para and meta derivatives)
Scheme 3. New synthetic route toward 1–6.

3788
G. Grelaud et al. / Tetrahedron Letters 51 (2010) 3786–3788
Table 1
Yields and selected spectral signatures of the propargylic triarylphosphines 1b–6b
mOH (cmÀ1
)
mC„C (cmÀ1
)
31P{1H }NMRb
13C{1H } NMR
1H NMR
a
a
Product
Yield (%)
dP (ppm)
dC„C (ppm)
dOH (ppm)
1b (para; n = 1)
2b (para; n = 2)
3b (para; n = 3)
4b (meta; n = 1)
5b (meta; n = 2)
6b (meta; n = 3)
72
68
63
71
75
68
3349 (vs)
3378 (vs)
3329 (vs)
3354 (vs)
3322 (vs)
3237 (vs)
2238 (w)
2229 (w)
2234 (w)
2247 (w)
2243 (w)
2291 (w)
À4.2
À4.4
À4.9c
À4.2
À4.5
À4.6c
95.8 (s), 82.3 (s)
95.7 (s), 82.2 (s)
98.5 (s), 80.8 (s)d
94.9 (s), 82.3 (s)
95.3 (s), 82.1 (s)
98.0 (s), 80.6 (s)d
2.53
3.11
4.53c
2.09
3.55
4.56c
Neat in KBr ( 2 cmÀ1).
Unless precised, all NMR were recorded in CDCl3.
In acetone-d6.
In DMSO-d6.
a
b
c
d
Table 2
Yields and selected spectral signatures of the ethynylated triarylphosphines 1–6
m„CH (cmÀ1
)
mC„C (cmÀ1
)
31P{1H} NMRb
13C{1H} NMR
1H NMR
a
a
Product
Yield (%)
dP (ppm)
dC„C (ppm)
d„CH (ppm)
1 (para; n = 1)
2 (para; n = 2)
3 (para; n = 3)
4 (meta; n = 1)
5 (meta; n = 2)
6 (meta; n = 3)
94
91
90
90
80
81
3286 (s)
3298 (s)
3288 (w)
3288 (s)
3288 (s)
2291 (w)
2106 (w)
2107 (w)
2107 (w)
2109 (w)
2109 (w)
2291 (w)
À4.1
À4.1
À4.2
À4.3
À4.3
À4.6
83.9 (s), 78.9 (s)
83.8 (s), 79.2 (s)
83.9 (s), 78.7 (s)
83.8 (s), 79.1 (s)
83.7 (s), 79.1 (s)
83.6 (s), 78.6 (s)
3.15
3.16
3.18
3.08
3.13
3.12
a
Neat in KBr ( 2 cmÀ1).
All NMR were recorded in CDCl3.
b
evidenced by characteristic 13C/1H NMR shifts and IR stretches.
Notably, 1–6 are more reactive substances than their propargylic
alcohol precursors 1b–6b. They slowly decompose and turn dark
upon standing at 25 °C under air and should therefore be stored
under inert atmospheres at low temperature or used as soon as
possible, once prepared.
References and notes
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In conclusion, we have reported here a new and general syn-
thetic route toward the ethynylated triphenylphosphine deriva-
tives 1–6 which allows obtaining these ligands in fair yields
(Table 2) after three steps from commercially available starting
materials. In contrast to the previous syntheses of 1 and related
compounds, the ethynyl fragment is presently introduced after
performing the phosphination reaction. This synthetic approach,
while limiting the formation of phosphine oxides or other unde-
sired side-products, allows a simple purification of the intermedi-
ates after each step. Regarding the known compound 1, the present
route stands the comparison with the previously reported synthe-
ses based on the trimethylsilylalkynyl precursor 7, without the
need for any solid state reactant. Considering the large array of
selective transformations existing for terminal alkynyl groups,
1–6 open a synthetic route toward various classes of new func-
tional phosphines for catalysis or supramolecular chemistry.
Acknowledgments
G.G. thanks Region Bretagne for a scholarship. The CNRS is
acknowledged for financial support.
14. Thomas, C. M.; Peters, C. J. Inorg. Chem. 2004, 43, 8–10.
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Chichester, 1997.
Supplementary data
Supplementary data (experimental details for the synthesis and
characterization data for various compounds) associated with this
article can be found, in the online version, at doi:10.1016/j.tetlet.
2010.05.055.