at carbon center.3 On the other hand, chiral phosphonium
salts bearing the chirality at phosphorus have been scarcely
reported in asymmetric reactions.3i This is due to the few
stereoselective methodologies allowing their easy preparation
and structural modifications. Over the past decade, asym-
metric synthesis of organophosphorus compounds has made
much progress due to the use of borane as P(III)-protecting
group.11,12
In connection with our ongoing work on asymmetric
synthesis of P-stereogenic phosphorus compounds,12 we
previously reported the preparation of chiral phosphonium
salts13 and their NMR enantiodifferentiation using BINPHAT
or liquid crystal.14 However, these methods are limited to
the quaternization by alkylhalides, whereas the synthesis of
P-stereogenic tetraaryl phosphonium salts is still unknown.
In the latter case, the quaternization requires harsh conditions
or high temperature nickel- or palladium-mediated P-C bond
formations,15 which are inappropriate with the configurational
stability of phosphines.16,17 Recently, new advances in the
field of arynes have been described, allowing their prepara-
tion under mild conditions based on the fluoride-induced 1,2-
elimination of (o-trimethylsilyl) aryl triflates 2.18 As elec-
trophilic species, arynes are well-known to readily react with
various types of nucleophiles.18-20
In a pioneering work, Wittig has shown that arynes
generated from 1,2-dihaloaryls can be used for the quater-
nization of phosphine.20 Preliminary investigations on the
reaction of triphenylphosphine with benzyne, generated from
1,2-dibromobenzene, led to tetraphenylphosphonium bromide
in 42% yield. The use of (o-trimethylsilyl)phenyl triflate 2a
to generate the transient benzyne species in the presence of
fluoride anions was then investigated for the quaternization
(Table 1). The proposed mechanism for this reaction is based
Table 1. Results of the Quaternization of Triphenylphosphine
1a with (o-Trimethylsilyl)phenyltriflate 2a
fluoride
source
(equiv)
t (°C), time yield (%)a
entry
solvent
THF
CH3CN
CH3CN
PhCH2CN
CH3CN
CH3CN
(h)
3a
1
2
3
4
5
6
7
8
9
10
CsF (3.3)b
CsF (3.3)b
CsF (6.0)c
CsF (6.0)c
CsF (6.0)c
LiF (6.0)c
25, 15
25, 15
25, 15
25, 15
60, 15
25, 15
25, 15
25, 15
25, 15
25, 15
18
38
89
51
58
0
We report here a new strategy for the preparation of chiral
and achiral phosphonium salts 3 based on the quaternization
of phosphines 1 with arynes generated from (o-trimethylsi-
lyl)aryl triflates 2.
NaF (6.0)c CH3CN
0
KF (6.0)c
CH3CN
32
23
0
CuF2 (6.0)c CH3CN
(10) (a) Zurawinski, R.; Donnadieu, B.; Mikolajczyk, M.; Chauvin, R.
J. Organomet. Chem. 2004, 689, 380–386. (b) Ohta, T.; Sasayama, H.;
Nakajima, O.; Kurahashi, N.; Fujii, T.; Furukawa, I. Tetrahedron: Asym-
metry 2003, 14, 537–542. (c) Leglaye, P.; Donadieu, B.; Brunet, J.-J.;
TBAF (6.0)c CH3CN
a Isolated yields after crystallization of the crude. b Reaction carried
out with 1.1 equiv of 2a. c Reaction carried out with 2.5 equiv of 2a.
Chauvin, R. Tetrahedron Lett. 1998, 39, 9179–9182
.
(11) (a) Andrushko, N.; Bo¨rner, A. In Phosphorous Ligands in Asym-
metric Catalysis; Borner, A., Ed.; Wiley-VCH: Weinheim, 2008; Vol. 3,
pp 1275-1347. (b) Crepy, K. V. L.; Imamoto, T. Top. Curr. Chem. 2003,
229, 1–40. (c) Al-Masum, M.; Kumaraswamy, G.; Livinghouse, T. J. Org.
Chem. 2000, 65, 4776–4778. (d) Wolfe, B.; Livinghouse, T. J. Am. Chem.
Soc. 1998, 120, 5116–5117. (e) Ohff, M.; Holz, J.; Quirmbach, M.; Bo¨rner,
A. Synthesis 1998, 139, 1–1415. (f) Muci, A. R.; Campos, K. R.; Evans,
D. A. J. Am. Chem. Soc. 1995, 117, 9075–9076. (g) Oshiki, T.; Imamoto,
on a first attack of the fluoride anion to the trimethylsilyl
group of 2a affording the benzyne intermediate by ꢀ-elim-
ination of the triflate. The trapping of the phosphine then
leads to a phosphonium anion that is protonated by aceto-
nitrile, giving 3a (Scheme 1).21
T. J. Am. Chem. Soc. 1992, 114, 3975–3977
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(12) (a) Darcel, C.; Uziel, J.; Juge´, S. In Phosphorous Ligands in
Asymmetric Catalysis; Borner, A., Ed.; Wiley-VCH: Weinheim, 2008; Vol.
3, pp 1211-1233. (b) Bauduin, C.; Moulin, D.; Kaloun, E. B.; Darcel, C.;
Juge´, S. J. Org. Chem. 2003, 11, 4293–4301. (c) Juge´, S.; Stephan, M.;
Laffitte, J. A.; Geneˆt, J. P. Tetrahedron Lett. 1990, 31, 6357–6360
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Scheme 1. Proposed Mechanism for the Quaternization
(13) (a) Meyer, F.; Uziel, J.; Papini, A.-M.; Juge´, S. Tetrahedron Lett.
2001, 42, 3981–3984. (b) Uziel, J.; Riegel, N.; Aka, B.; Figuie`re, P.; Juge´,
S. Tetrahedron Lett. 1997, 38, 3405–3408.
(14) (a) Meddour, A.; Uziel, J.; Courtieu, J.; Juge´, S. Tetrahedron:
Asymmetry 2006, 17, 1424–1429. (b) Hebbe, V.; Londez, A.; Goujon-
Ginglinger, C.; Meyer, F.; Uziel, J.; Juge´, S.; Lacour, J. Tetrahedron Lett.
2003, 44, 2467–2471. (c) Goujon-Ginglinger, C.; Jeannerat, D.; Lacour, J.;
Juge´, S.; Uziel, J. Tetrahedron Lett. 1998, 39, 7495–7498.
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593. (b) Tebby, J.-C.; Allen, D. W. Sci. Synth. 2007, 31b, 2083–2104. (c)
Shevchuck, M. I.; Bukachuk, O. M.; Zinzyuk, T.A. J. Gen. Chem. USSR
1985, 55, 304–306. (d) Migita, T.; Nagai, T.; Kiuchi, K.; Kosugi, M. Bull.
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Hoffmann, H. Chem. Ber. 1958, 91, 45–49.
After optimization, CsF (6 equiv) was identified as the
best fluoride source to generate benzyne from excess of 2a
(2.5 equiv) at room temperature in acetonitrile. Under these
conditions, the corresponding tetraphenyl phosphonium tri-
flate 3a was isolated in 89% yield (Table 1, entry 3).
These optimized conditions were then applied for the
quaternization of various P(III)-phosphorus compounds by
benzyne (Table 2). Aryl- or alkylphosphines 1b-e led to
the corresponding phenylphosphonium triflates 3b-e in
68-95% isolated yields (Table 2, entries 1-4 and 6). In the
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