Palladium-catalyzed synthesis of functionalized tetraarylphosphonium salts

Article abstract of DOI:10.1021/jo702355c

(Chemical Equation Presented) An efficient method to synthesize functionalized tetraarylphosphonium salts is described. This palladium-catalyzed coupling reaction between aryl iodides, bromides, or triflates and triphenylphosphine generates phosphonium salts in high yields. The coupling is compatible with a variety of functional groups such as alcohols, ketones, aldehydes, phenols, and amides.

Full text of DOI:10.1021/jo702355c

Palladium-Catalyzed Synthesis of Functionalized
Tetraarylphosphonium Salts
David Marcoux and Andre´ B. Charette*
De´partement de Chimie, UniVersite´ de Montre´al, P.O. Box 6128, Station Downtown,
Montre´al QC, Canada H3C 3J7
andre.charette@umontreal.ca
ReceiVed October 31, 2007
An efficient method to synthesize functionalized tetraarylphosphonium salts is described. This palladium-
catalyzed coupling reaction between aryl iodides, bromides, or triflates and triphenylphosphine generates
phosphonium salts in high yields. The coupling is compatible with a variety of functional groups such
as alcohols, ketones, aldehydes, phenols, and amides.
Introduction
anticancer agents9,10 and as drug carriers.11 Some tetraarylphos-
phonium (TAP) salts also possess some significant bioactivity;10
however, their preparation is very tedious. Furthermore, there
is no simple or general catalytic method for the synthesis of
functionalized TAP.12
Our group has recently reported the use of functionalized TAP
as solubility control groups for reagents and synthesis. The
covalent binding of TAP to a reagent or catalyst renders the
latter soluble in solvents such as dichloromethane. The supported
reagent or catalyst is then easily separated from the reaction
Phosphonium salts have gained major importance in recent
years. They are versatile compounds that have been used as
catalyst transfer agents,1 organic reagents,2 ionic liquids,3
conducting agents,4 and flame-proofing agents.5,6 Aryl-substi-
tuted phosphonium salts, which are lipophilic cations, have
become increasingly popular in cellular biology.7 Alkyltri-
arylphosphonium salts have been shown to accumulate in
mitochondria of specific organs8 and have thus been studied as
(1) (a) Sefkow, M.; Borsuk, N.; Wolff, M. O. Chim. Oggi 2001, 19, 19.
(b) Manabe, K. Tetrahedron 1998, 54, 14465. (c) Manabe, K. Tetrahedron
Lett. 1998, 39, 5807.
(7) Ross, M. F.; Kelso, G. F.; Blaikie, F. H.; James, A. M.; Cocheme´,
H. M.; Filipovska, A.; Da Ros, T.; Hurd, T. R.; Smith, R. A. J.; Murphy,
M. P. Biochemistry (Moscow) 2005, 70, 222.
(8) Smith, R. A. J.; Porteous, C. M.; Gane, A. M.; Murphy, M. P. Proc.
Natl. Acad. Sci. U.S.A. 2003, 100, 5407.
(9) Rideout, D. C.; Calogeropoulou, T.; Jworski, J. S.; Dagnino, R.;
McCarthy, M. R. Anti-Cancer Drug Des. 1989, 4, 265.
(10) Rideout, D.; Bustmante, A.; Patel, J. Int. J. Cancer 1994, 57, 247.
(11) (a) Fantin, V. R.; Leder, P. Oncogene 2006, 25, 4787. (b) Sheu,
S.-S.; Nauduri, D.; Anders, M. W. Biochim. Biophys. Acta 2006, 1762,
256. (c) Modica-Napolitano, J. S.; Aprille, J. R. AdV. Drug DeliVery ReV.
2001, 49, 63. (d) Adlam, V. J.; Harrison, J. C.; Porteous, C. M.; James, A.
W.; Smith, R. A. J.; Murphy, M. P.; Sammut, I. A. FASEB J. 2005, 19,
1088. (e) Smith, R. A.; Kelso, G. F.; James, A. M.; Murphy, M. P. Methods
Enzymol. 2004, 382, 45. (f) Smith, R. A.; Porteous, C. M.; Coulter, C. V.;
Murphy, M. P. Eur. J. Biochem. 1999, 263, 709. (g) Siler-Marsiglio, K. I.;
Pan, Q.; Paiva, M.; Madorsky, I.; Khurana, N. C.; Heaton, M. B. Brain
Res. 2005, 1052, 202.
(2) Wittig olefination: (a) Rein, T.; Pederson, T. M. Synthesis 2002,
579. (b) Hoffmann, R. W. Angew. Chem., Int. Ed. 2001, 40, 1411. (c)
Cristau, H.-J. Chem. ReV. 1994, 94, 1299. (d) Maryanoff, B. E.; Reitz, A.
B. Chem. ReV. 1989, 89, 863. (e) Maercker, A. Org. React. 1965, 14, 270.
PPh3Br2 reagent: (f) Castro, B. R. Org. React. 1983, 29, 1.
(3) Selected review on ionic liquid: (a) Dupont, J.; de Souza, R. F.;
Suarez, P. A. Z. Chem. ReV. 2002, 102, 3667. (b) Tzschucke, C. C.; Markert,
C.; Roller, S.; Hebel, A.; Haag, R.; Bannwarth, W. Angew. Chem., Int. Ed.
2002, 41, 3964. (c) Wasserscheid, P.; Keim, W. Angew. Chem., Int. Ed.
2000, 39, 3772.
(4) (a) Akutsu, H.; Yamada, J.-I.; Nakatsuji, S. Chem. Lett. 2003, 32,
1118. (b) Akutsu, H.; Yamada, J.-I.; Nakatsuji, S. Chem. Lett. 2001, 29,
208. (c) Akutsu, H.; Yamada, J.-I.; Nakatsuji, S. Synth. Met. 2001, 120,
871.
(5) Beck, P. In Organic Phosphorus Compounds; Kosolapoff, G. M.,
Maier, L., Eds.; Wiley-Interscience: New York, 1972; Vol. 2, and references
cited therein.
(6) For other application of tetraphenylphosphonium salts: Sefkow, M.;
Borsuk, N.; Wolff, M. O. Chim. Oggi 2001, 19, 35.
(12) Review on the synthesis of tetraarylphosphonium salts: (a) Allen,
D. W. Organophosphorus Chem. 2003, 33, 1. (b) Beletskaya, I. P.;
Kazankova, M. A. Russ. J. Org. Chem. 2002, 38, 1391.
10.1021/jo702355c CCC: $40.75 © 2008 American Chemical Society
Published on Web 12/23/2007
590
J. Org. Chem. 2008, 73, 590-593

Synthesis of Functionalized Tetraarylphosphonium Salts
SCHEME 1. Preliminary Results
product by precipitation upon an etheral solvent such such as
diethyl ether. A number of TAP-supported reagents such as
triphenylphosphine and diazocarboxylate derivatives13 and tin
reagents14 were prepared and utilized in various reactions. We
have also used TAP as a soluble support in the synthesis of
small molecules to allow isolation by a precipitation.15
The classical methods for the preparation of TAP typically
employ metal-free conditions which require high temperature
and/or harsh reaction conditions.16,17
TABLE 1. Optimization of the Coupling Conditions
More conveniently, the synthesis of TAP was accomplished
with transition metal catalysts and reagents. Nickel(II)-mediated
synthesis of TAP requires high nickel loading (50 mol %)18 or
an o-imine substituent.19 Nickel(0)-catalyzed reactions are
effective only with strongly electron-donating substituents on
the aryl halide component (OMe, NMe2),20 high catalyst loading
(10-35 mol %), and/or tedious purification.1b,c Palladium-
catalyzed formation of TAP21 was first reported by Heck, who
observed the presence of TAP as a byproduct in a palladium-
catalyzed reaction.22 Subsequently, Migita developed a pal-
ladium-catalyzed (using Pd(OAc)2) synthesis of TAP limited
to aryl iodides.23 To date, no efficient method is known for the
palladium-catalyzed synthesis of TAP from aryl bromides or
triflates.24 Herein, we report a palladium-catalyzed reaction for
the synthesis of functionalized TAP from aryl bromides, iodides,
and triflates.
entry
precatalyst
solvent (concn, M)
time (h)
yield (%)a
1
2
3b
4
5c
6b,d
7b,f
8
Pd(OAc)2
Pd(PPh3)4
Pd2(dba)3
Pd on C
o-xylene (0.5)
o-xylene (0.5)
o-xylene (0.5)
o-xylene (0.5)
o-xylene (0.5)
o-xylene (0.5)
o-xylene (0.5)
o-xylene (1)
o-xylene (2)
o-xylene (3)
o-xylene (4)
o-xylene (3)
p-xylene (3)
ethylbenzene (3)
benzonitrile (3)
o-xylene (3)
o-xylene (3)
48
48
48
48
48
48
48
4
4
4
4
5
80
82
86
20
9
94e
49
56
83
91
70
95
92
88
91
54
80
PdCl2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
9
10
11
12
13
14
15
16g
17h
(13) Poupon, J.-C.; Boezio, A. A.; Charette, A. B. Angew. Chem., Int.
Ed. 2006, 45, 1415.
(14) Poupon, J.-C.; Marcoux, D. M.; Cloarec, J.-M.; Charette, A. B. Org.
Lett. 2007, 9, 3591.
(15) Stazi, F.; Marcoux, D.; Poupon, J.-C.; Latassa, D.; Charette, A. B.
Angew. Chem., Int. Ed. 2007, 46, 5011.
5
5
5
5
5
(16) Ipso substitution: (a) Shevchuck, M. I.; Bukachuk, O. M.; Zinzyuk,
T. A. J. Gen. Chem. USSR 1985, 55, 304. (b) Shevchuck, M. I.; Bukachuk,
O. M. J. Gen. Chem. USSR 1982, 52, 721. (c) Bukachuk, O. M.; Megera,
I. V.; Porushnik, M. I.; Shevchuk, M. I. J. Gen. Chem. USSR, 1980, 50,
1404. (d) McDonald, R. N.; Campbell, T. W. J. Am. Chem. Soc. 1960, 82,
4669.
a Isolated yield. b 0.5 mol % was used with Pd2(dba)3. c 0.02 equiv of
Et3N was added. d 0.5 equiv of triphenylphosphine was used instead of 1
equiv. e Yield based on the limiting reagent: triphenylphosphine. f 2 equiv
of triphenylphosphine was used instead of 1 equiv. g The reaction was run
at 125 °C. h The reaction was run at 135 °C.
(17) From aryldiazonium: Horner, L.; Hoffmann, H. Chem. Ber. 1958,
91, 45.
(18) (a) Horner, L.; Duda, U.-M. Tetrahedron Lett. 1970, 59, 5177. (b)
Horner, L.; Mummenthey, G.; Moser, H.; Beck, P. Chem. Ber. 1966, 99,
2782. (c) Hirusawa, Y.; Oku, M.; Yamamoto, R. Bull. Chem. Soc. Jpn.
1957, 30, 667.
Results and Discussion
We began our studies using the method described by Migita
(Scheme 1).23 Excellent yields were obtained with iodobenzene;
however, only trace amounts (ca. 10%) of phosphonium salt
2b were obtained after 24 h at 120 °C. Increasing the reaction
time to 48 h led to only a slight improvement in yield (25%).
Interestingly, increasing the temperature to 130 °C gave a 94%
yield of phosphonium 2b albeit in 48 h (Scheme 1).
(19) (a) Allen, D. W.; Cropper, P. E.; Nowell, I. W. Polyhedron 1999,
18, 1039. (b) Allen, D. W.; Cropper, P. E. Polyhedron 1990, 9, 129. (c)
Allen, D. W.; Cropper, P. E.; Nowell, I. W. J. Chem. Res. 1987, 298. (d)
Allen, D. W.; Cropper, P. E.; Smithurst, P. G.; Ashton, P. R.; Taylor, B. F.
J. Chem. Soc., Perkin Trans. 1 1986, 1989. (e) Allen, D. W.; Nowell, I.
W.; March, L. A.; Taylor, B. F. J. Chem. Soc., Perkin. Trans. 1 1984, 2523.
(f) Allen, D. W.; Nowell, I. W.; March, L. A.; Taylor, B. F. Tetrahedron
Lett. 1982, 23, 5479. (g) Allen, D. W.; Light, M. E.; Hursthouse, M. B. J.
Chem. Res. 2002, 537. (h) Allen, D. W.; Coles, S. J.; Hursthouse, M. B. J.
Chem. Res. 2000, 71. (i) Allen, D. W.; Hibbs, D. E.; Hursthouse, M. B.;
Abdul Malik, K. M. J. Organomet. Chem. 1999, 572, 259. (j) Dai, X.; Wong,
A.; Virgil, S. C. J. Org. Chem. 1998, 63, 2597. (k) Allen, D. W.; Hawkrigg,
J.; Adams, H.; Taylor, B. F.; Hibbs, D. E.; Hursthouse, M. B. J. Chem.
Soc., Perkin Trans. 1 1998, 335. (l) Allen, D. W.; Li, X. J. Chem. Soc.,
Perkin Trans. 2 1997, 1099. (m) Allen, D. W.; Benke, P. J. Chem. Soc.,
Perkin Trans. 1 1995, 2789.
Encouraged by these results, we undertook a careful optimi-
zation of the coupling reaction between triphenylphosphine and
bromobenzene (Table 1). Several palladium pre-catalysts [Pd-
(OAc)2, PdCl2, Pd2(dba)3, Pd/C] were screened (entries 1-5)
and Pd2(dba)3 produced the best yield (entry 3). Varying the
amount of triphenylphosphine showed that lowering it to 0.5
(20) Cassar, L.; Foa`, M. J. Organomet. Chem. 1974, 74, 75.
(21) For vinyltriphenylphosphonium see: (a) Huang, Ch.-Ch.; Duan, J.-
P.; Wu, M.-Y.; Liao, F.-L.; Wang, S.-L.; Cheng, Ch.-H. Organometallics
1998, 17, 676. (b) Hinkle, R. J.; Stang, P. J.; Kovalsk, M. H. J. Org. Chem.
1990, 55, 5033. (c) Stang, P. J.; Kovalsky, M. H.; Schiavelli, M. D.;
Longford, D. J. Am. Chem. Soc. 1989, 111, 3347. (d) Kovalsky, M. H.;
Hinkle, T. J.; Stang, P. J. J. Org. Chem. 1989, 54, 2783.
(22) (a) Ziegler, C. B.; Heck, R. F. J. Org. Chem. 1978, 43, 2941. (b)
Melpoder, J. B.; Heck, R. F. J. Org. Chem. 1976, 41, 265.
(23) (a) Migita, T.; Nagai, T.; Kiuchi, K.; Kosugi, M. Bull. Chem. Soc.
Jpn. 1983, 56, 2869. (b) Migita, T.; Shimizu, T.; Asami, Y.; Shiobara, J.;
Kato, Y.; Kosugi, M. Bull. Chem. Soc. Jpn. 1980, 53, 1385.
(24) Aryl iodides have been the most utilized: (a) Cheng, Z.; Subbarayan,
M.; Chen, X.; Gambhir, S. S. J. Labelled Compd. Radiopharm. 2005, 48,
131. (b) De la Torre, G.; Gouloumis, A.; Vazquez, P.; Torres, T. Angew.
Chem., Int. Ed. 2001, 40, 2895. (c) Bourgogne, C.; Le Fur, Y.; Juen, P.;
Masson, P.; Nicoud, J.-F.; Masse, R. Chem. Mater. 2000, 12, 1025. (d)
Vicente, J.; Abad, J.-A.; Frankland, A. D.; Carmen, R. M. Chem. Eur. J.
1999, 5, 3066. (e) Clark, J. H.; Tavener, S. J.; Barlow, S. J. J. Mater. Chem.
1995, 5, 827. (f) Lambert, C.; Gaschler, W.; Noll, G.; Weber, M.;
Schmalzlin, E.; Brauchle, C.; Meerholz, K. J. Chem. Soc., Perkin Trans. 2
2001, 964. From aryl bromides: (g) Clark, J. H.; Tavener, S. J.; Barlow, S.
J. J. Mater. Chem. 1995, 5, 827.
J. Org. Chem, Vol. 73, No. 2, 2008 591

Marcoux and Charette
SCHEME 3. Reaction with Other Activated Aryl
SCHEME 2. Reaction with Functionalized Aryl Bromides
reaction times for aryl iodides and triflates. In addition to making
aryl bromides react, these reaction conditions give better yield
in shorter reaction time (30 min vs 25 h) compare to Migita’s
condition.23 However, aryl chlorides did not react under these
conditions.
To explore the scope of the reaction, several aryl bromides,
iodides, and triflates were subjected to the optimized reaction
conditions (Table 2).
equiv accelerated the reaction (entry 6) while increasing it to 2
equiv gave lower yield (entry 7). However, a one-to-one ratio
of bromobenzene and triphenylphosphine was kept for the rest
of the optimization. The concentration of the reaction was also
found to be extremely important for further improvement (entries
8-11) since varying the concentration of reagent from 0.5 to 3
M gave a nearly quantitative yield of desired TAP 2b in only
5 h (entry 12). Since the phosphonium salt generated is not
soluble in o-xylene, product isolation requires a simple filtration
of the reaction mixture followed by diethyl ether (or tert-butyl
methyl ether) trituration of the solid to remove any traces of
unreacted starting material. A screening of the solvent indicated
that other aromatic solvents could be used such as benzonitrile.
In the latter, the reaction is homogeneous, which makes the
isolation of the product and the solvent removal less practical.
This solvent, however, could not be used with functionalized
substrates (vide infra). The optimal temperature was shown to
be 145 °C (entries 10, 16, and 17).
When two sets of optimized conditions (Table 1, entries 12
and 15) were applied to a substituted aryl bromide, an important
side reaction was observed when benzonitrile was used as
solvent (Scheme 2). The palladium-catalyzed coupling of
4-bromo-4′-formylbiphenyl (3b) with triphenylphosphine in
benzonitrile led to the desired product 4b that was contaminated
with significant amounts of tetraphenylphosphonium bromide
(2b). It is believed that this side product is formed from the
oxidative addition of Pd(0) into the phosphonium-phenyl bond,
followed by the reductive elimination with triphenylphosphine
to afford phosphonium 2b.25 Chang has recently shown that
tetraarylphosphonium salts can be used as electrophilic partners
in several palladium-catalyzed processes.26 This reaction has
been utilized as a key feature to make phosphines.27 Fortunately,
the formation of this byproduct was completely suppressed when
switching the solvent from benzonitrile to o-xylene. It is believed
that the heterogeneous nature of the reaction in o-xylene plays
a key role in the minimization of the byproduct formation by
making the phosphonium salt less available to undergo further
oxidative addition with palladium(0).
Various TAP salts containing an aryl group bearing an
electron-donating substituent at the meta or para position were
prepared in excellent yields (products 9, 10, 12, and 13). Aryl
halides bearing ortho substituents could not be efficiently
coupled with triphenylphosphine under these conditions. Several
functional groups such as alcohols (entry 2), aldehydes (entry
3), amides (entry 4), and ketones (entry 8) are well tolerated
under the reaction conditions. The reactions proceeded very well
with aryl bromides, iodides, or triflates, but the reaction times
were significantly shorter with the latter. When a dibromo
compound was used as a starting material, it was possible to
stop the reaction at the monophosphonium stage (see compounds
5 and 14), a process that was not possible to achieve using
Horner’s conditions.18 Functional groups that are so far not
tolerated include carboxylic acids and esters.
It is also possible to use the monobromoaryltriphenylphos-
phonium salt in a subsequent palladium-catalyzed cross-coupling
reaction. For example, Stille coupling of aryl bromide 5 with
Fu’s condition28 afforded phosphonium salt 15 in 89% yield
(Scheme 4). Phosphonium 15 is an intermediate in the synthesis
of supported tin reagents that previously required 5 steps from
commercially available 4,4′-dibromobiphenyl using Horner’s
procedure.18
In conclusion, we have developed an efficient method to
generate functionalized TAP. The palladium-catalyzed reaction
gives excellent yields for the coupling reaction of aryl halides
or triflates and triphenylphosphine. Aryl iodides, triflates, and
bromides can be efficiently used under the reaction condition.
The ease of purification by simple precipitation/filtration also
makes this method very convenient. Efforts to increase the
functional group tolerance are under study and will be reported
in due course.
These optimized conditions were effective not only with aryl
bromides but also with aryl iodides and triflates (Scheme 3).
Excellent yields of the desired products were obtained in shorter
Experimental Section
Typical Procedure for the Synthesis of TAP Iodides. Iodo-
benzene (1.22 g, 669 µL, 6 mmol, 1.0 equiv), Pd2(dba)3 (55.0 mg,
0.06 mmol, 1 mol %) weighted in a glovebox, and triphenylphos-
phine (1.57 g, 6.0 mmol, 1 equiv) were mixed together in a dry 50
mL tube under inert atmosphere (Argon) of a combinatorial
chemistry kit equipped with a condenser. To this mixture were
added dry o-xylene (2 mL, 3 M) and a magnetic stir bar. The
reaction mixture was heated to reflux for 1 h under argon. The
phosphonium salts precipitated as the reaction proceeded. After 1
(25) Goodson, F. E.; Wallow, T. I.; Novak, B. M. J. Am. Chem. Soc.
1997, 119, 12441 and reference cited therein.
(26) Hwang, L. K.; Na, Y.; Lee, J.; Do, Y.; Chang, S. Angew. Chem.,
Int. Ed. 2005, 44, 6166.
(27) (a) Wang, Y.; Lai, C. W.; Kwong, F. Y.; Jia, W.; Chan, K. S.
Tetrahedron 2004, 60, 9433. (b) Kwong, F. Y.; Lai, C. W.; Yu, M.; Tian,
Y.; Chan, K. S. Tetrahedron 2003, 59, 10295. (c) Kwong, F. Y.; Lai, C.
W.; Chan, K. S. Tetrahedron Lett. 2002, 43, 3537. (d) Lai, C. W.; Kwong,
F. Y.; Wang, Y.; Chan, K. S. Tetrahedron Lett. 2001, 42, 4883. (e) Kwong,
F. Y.; Lai, C. W.; Tian, Y.; Chan, K. S. Tetrahedron Lett. 2000, 41, 10285.
(f) Kwong, F. Y.; Chan, K. S. Chem. Commun. 2000, 12, 1069.
(28) Littke, A. F.; Schwarz, L.; Fu, G. C. J. Am. Chem. Soc. 2002, 124,
6343.
592 J. Org. Chem., Vol. 73, No. 2, 2008

Synthesis of Functionalized Tetraarylphosphonium Salts
TABLE 2. Scope of the Coupling Reaction
MHz, CDCl3) δ 23.3; IR 3065 (br), 3062, 1585, 1483, 1435, 1262,
1141, 1107, 1030, 995, 905 (film) cm-1; HRMS (ES, Pos) calcd
for C24H20P1 [M]+ 339.1302, found 339.1288; HRMS (ES, Neg)
calcd for 127I [M]- 126.9056, found 126.9050.
Typical Procedure for the Synthesis of TAP Bromides.
Bromobenzene (942 mg, 632 µL, 6 mmol, 1.0 equiv), Pd2(dba)3
(55.0 mg, 0.06 mmol, 1 mol %) weighted in a glovebox, and
triphenylphosphine (1.57 g, 6.0 mmol, 1 equiv) were mixed together
under inert atmosphere (Argon) in a dry 50 mL tube of a
combinatorial chemistry kit equipped with a condenser. To this
mixture were added dry o-xylene (2 mL, 3 M) and a magnetic stir
bar. The reaction mixture was heated to reflux for 5 h under argon.
The phosphonium salts precipitated as the reaction proceeded. After
5 h, the tube was cooled to room temperature, 20 mL of diethyl
ether was added, and the resulting suspension was stirred at room
temperature for 2 min. The precipitate was filtered on Celite and
silica gel and washed with 50 mL of diethyl ether. The phosphonium
salt was dissolved with DCM into a 200 mL round-bottomed flask.
The organic phase was concentrated under reduced pressure to
afford pure 2b as a pure white solid (2.39 g, 95% yield). Mp >250
°C (288);23 1H NMR (300 MHz, CDCl3) δ 7.90-7.81 (m, 4H),
7.76-7.69 (m, 8H), 7.60-7.53 (m, 8H); 13C NMR (75 MHz,
CDCl3) δ 135.8 (d, J ) 3.0 Hz, 4C), 134.4 (d, J ) 10.3 Hz, 8C),
130.8 (d, J ) 12.9 Hz, 8C), 117.4 (d, J ) 89.6 Hz, 4C); 31P NMR
(122 MHz, CDCl3) δ 23.3; IR 3065 (br), 3062, 1585, 1483, 1435,
1262, 1141, 1107, 1030, 995, 905 (film) cm-1; HRMS (ES, Pos)
calcd for C24H20P1 [M]+ 339.1302, found 339.1288; LRMS (ES,
Neg) calcd for 79Br [M]- 78.9, found 79.0; calcd for 81Br [M]-
80.9, found 81.0.
Typical Procedure for the Synthesis of TAP Triflates. Phenyl
trifluoromethanesulfonate (1.36 g, 6 mmol, 1.0 equiv), Pd2(dba)3
(55.0 mg, 0.06 mmol, 1 mol %) weighted in a glovebox, and
triphenylphosphine (1.57 g, 6.0 mmol, 1 equiv) were mixed together
in a dry 50 mL tube under inert atmosphere (argon) of a
combinatorial chemistry kit equipped with a condenser. To this
mixture were added dry o-xylene (2 mL, 3 M) and a magnetic stir
bar. The reaction mixture was heated to reflux for 1 h under argon.
The phosphonium salts precipitated as the reaction proceeded. After
1 h, the tube was cooled to room temperature, 20 mL of diethyl
ether was added and the resulting suspension was stirred at room
temperature for 2 min. The precipitate was filtered on Celite and
silica gel and washed with 50 mL of diethyl ether. The phosphonium
salt was dissolved with DCM into a 200 mL round-bottomed flask.
The organic phase was concentrated under reduced pressure to
afford 2c as a pure white solid (2.81 g, 96% yield): mp >250 °C;
1H NMR (300 MHz, CDCl3) δ 7.90-7.81 (m, 4H), 7.76-7.69 (m,
8H), 7.60-7.53 (m, 8H); 13C NMR (75 MHz, CDCl3) δ 135.8 (d,
J ) 3.0 Hz, 4C), 134.4 (d, J ) 10.3 Hz, 8C), 130.8 (d, J ) 12.9
Hz, 8C), 117.4 (d, J ) 89.6 Hz, 4C); 31P NMR (122 MHz, CDCl3)
δ 23.3; 19F NMR (282 MHz, CDCl3) δ -79.5; IR 3065 (br), 3062,
a Reaction times: 5 h for aryl bromide, 1 h for aryl iodide, and 2 h for
aryl triflates. b Isolated yields. c 2 h of reaction time. d 3 h of reaction time.
e Monophosphonium salt was formed exclusively.
SCHEME 4. Utility of TAP 5
1585, 1483, 1435, 1262, 1141, 1107, 1030, 995, 905 (film) cm-1
;
HRMS (ES, Pos) calcd for C24H20P1 [M]+ 339.1302, found
339.1288; HRMS (ES, Neg) calcd for CF3SO3 [M]- 148.9532,
found 148.9525.
Acknowledgment. This work was supported by NSERC
(Canada), VRQ, Univalor, the Canada Research Chair Program,
and the Universite´ de Montre´al. D.M. is grateful to NSERC
(ES D) for a postgraduate fellowship, and the Universite´ de
Montre´al for a postgraduate fellowship.
h, the tube was cooled to room temperature, 20 mL of diethyl ether
was added, and the resulting suspension was stirred at room
temperature for 2 min. The precipitate was filtered on Celite and
silica gel and washed with 50 mL of diethyl ether. The phosphonium
salt was dissolved with DCM into a 200 mL round-bottomed flask.
The organic phase was concentrated under reduced pressure to
afford 2a as a pure white solid (2.66 g, 95% yield): mp >250 °C
(346);23 1H NMR (300 MHz, CDCl3) δ 7.90-7.81 (m, 4H), 7.76-
7.69 (m, 8H), 7.60-7.53 (m, 8H); 13C NMR (75 MHz, CDCl3) δ
135.8 (d, J ) 3.0 Hz, 4C), 134.4 (d, J ) 10.3 Hz, 8C), 130.8 (d,
J ) 12.9 Hz, 8C), 117.4 (d, J ) 89.6 Hz, 4C); 31P NMR (122
Supporting Information Available: Experimental procedures
for the preparation of all the compounds and characterization data
for each reaction and detailed structural assignment. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO702355C
J. Org. Chem, Vol. 73, No. 2, 2008 593