Rapid formation of triarylphosphines by microwave-assisted transition metal-catalyzed C-P cross-coupling reactions

Article abstract of DOI:10.1021/ol026716b

(matrix presented) Rapid, direct transition metal-catalyzed C-P(III) cross-coupling reactions were performed by microwave dielectric heating, employing diphenylphosphine and aryl halides/triflates as substrates. Depending on the specific aryl halide/triflate precursor, the highest yields were obtained utilizing heterogeneous or homogeneous Pd or Ni catalysts in DMF or NMP in the presence of KOAc or DABCO as a base.

Full text of DOI:10.1021/ol026716b

ORGANIC
LETTERS
2
002
Vol. 4, No. 20
541-3543
Rapid Formation of Triarylphosphines
by Microwave-Assisted Transition
Metal-Catalyzed C−P Cross-Coupling
Reactions
3
Alexander Stadler and C. Oliver Kappe*
Institute of Chemistry, Karl-Franzens-UniVersity Graz, Heinrichstrasse 28,
A-8010 Graz, Austria
oliVer.kappe@uni-graz.at
Received August 12, 2002
ABSTRACT
Rapid, direct transition metal-catalyzed C−P(III) cross-coupling reactions were performed by microwave dielectric heating, employing
diphenylphosphine and aryl halides/triflates as substrates. Depending on the specific aryl halide/triflate precursor, the highest yields were
obtained utilizing heterogeneous or homogeneous Pd or Ni catalysts in DMF or NMP in the presence of KOAc or DABCO as a base.
Tertiary phosphines are very important types of ligands in
transition metal-catalyzed reactions. Among the various
Scheme 1
methods for the synthesis of such phosphine ligands, direct
carbon-phosphorus (C-P) bond formation via transition
metal-catalyzed cross-coupling of unprotected secondary
phosphines with aryl halides/triflates can be considered as
1
-6
one of the most valuable procedures (Scheme 1).
In
contrast to most other C-P bond-forming protocols, no
(
1) Brauer, D. J.; Hingst, M.; Kottsieper, K. W.; Liek, C.; Nickel, T.;
Tepper, M.; Stelzer, O.; Sheldrick, W. S. J. Organomet. Chem. 2002, 645,
4-26 and references therein.
2) (a) Herd, O.; Hessler, A.; Hingst, M.; Trepper, M.; Stelzer O. J.
introduction of protection groups at phosphorus is required
for this one-pot tertiary phosphine synthesis and the method
is compatible with a variety of functional groups. The first
1
(
1
Organomet. Chem. 1996, 522, 69-76. (b) Machnitzki, P.; Nickel, T.; Stelzer,
O.; Landgrafe, C. Eur. J. Inorg. Chem. 1998, 1029-1034.
successful Pd-catalyzed couplings of aryl iodides/bromides
with diarylphosphines were reported by Stelzer and co-
(3) Cai, D.; Payack, J. F.; Bender, D. R.; Hughes, D. L.; Verhoeven, T.
R.; Reider, P. J. J. Org. Chem. 1994, 59, 7180-7181; Org. Synth. 1998,
6, 6-10.
4) Bergbreiter, D. E.; Liu, Y.-S.; Furyk, S.; Case, B. L. Tetrahedron
Lett. 1998, 39, 8799-8802.
5) (a) Kraatz, H.-B.; Pletsch, A. Tetrahedron: Asymmetry 2000, 11,
2
7
workers in 1996. Similarly, a group from Merck disclosed
(
the use of a Ni catalyst for the direct phosphination of aryl
triflates with diphenylphosphine, a procedure that was applied
(
1
617-1621. (b) Skoda-Foldes, R.; Banffy, L.; Horvath, J.; Tuba, Z.; Kollar,
to the preparation of the diphosphine ligand 2,2′-bis-
L. Monatsh. Chem. 2000, 131, 1363-1369. (c) Saxon, E.; Armstrong, J.
I.; Bertozzi, C. R. Org. Lett. 2000, 2, 2141-2143. (d) Armspach, D.; Matt,
D. Chem. Commun. 1999, 1073-1074.
3
(
diphenylphosphino)-1,1′-binaphthyl (BINAP). Since then,
a number of related protocols based on the Stelzer or Merck
C-P coupling methods have been developed, making a
number of functionalized triarylphosphine ligands accessible
(6) (a) Lacey, P. M.; McDonnell, C. M.; Guiry, P. J. Tetrahedron Lett.
2
000, 41, 2475-2478. (b) Martorell, G.; Garc ´ı as, X.; Janura, M.; Sa a´ . J.
M. J. Org. Chem. 1998, 63, 3463-3467.
1
0.1021/ol026716b CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/04/2002

by this route.1
,4-6
All of these protocols utilize a homoge-
tions utilized combinations of NMP, KOAc, and 2.5 mol %
of Pd(OAc) as catalyst (Table 1). A 50% excess of
neous transition metal catalyst and a base and generally
require many hours of reaction time at high temperatures or
otherwise impractical or complex synthetic manipulations
2
(
the synthesis of BINAP using the Merck protocol, for
Table 1. Microwave-Enhanced Synthesis of
example, requires multiple addition of reagents and 2-3 days
reaction time at 100 °C under an inert atmosphere).
Triphenylphosphine from Iodobenzene and Diphenylphosphine
3
as a Homogeneous Catalysta
Using Pd(OAc)
2
In the past few years, the utilization of microwave heating
in transition metal-catalyzed transformations has attracted
considerable interest. Many Pd- or Mo-catalyzed reactions
PhI
temp
(°C)
time
yield
(%)
entry
(mmol)
(min)
7
1
2
3
4
5
6
7
8
0.50
0.50
0.60
0.60
0.75
0.75
0.75
0.75
200
200
180
180
160
180
200
220
10
20
10
20
20
20
20
20
44
48
65
83
88
90
92
67
that typically need hours or days to reach completion with
conventional heating can be brought to full conversion in
only minutes utilizing microwave heating. Microwave-
mediated protocols in this area include the formation of a
variety of carbon-carbon as well as carbon-heteroatom
bond systems, utilizing, for example, Heck, Suzuki, Stille,
7
Sonogashira, Negishi, and Buchwald-Hartwig chemistry.
To the best of our knowledge, however, transition metal-
catalyzed C-P(III) bond formations utilizing high-speed
microwave chemistry have not been described. Herein we
report our preliminary investigations on rapid, homogeneous
and heterogeneous Pd- and Ni-catalyzed C-P couplings
involving aryl halides/triflates and diphenylphosphine.
The conventional coupling protocols involving iodo- and
bromobenzenes and secondary phosphines, reported by
a
Reactions were carried out in NMP (1.0 mL) with 0.50 mmol of Ph2PH
in the presence of KOAc (0.50 mmol) and Pd(OAc)2 (2.5 mol %, 2.8 mg).
For details, see Supporting Information.
iodobenzene was found to give the best yields (entries 5-8).
Within 20 min, a conversion of >90% was achieved at 180-
00 °C (entries 6 and 7). At higher temperatures, decomposi-
tion of the Pd(II) catalyst was observed, resulting in lower
isolated product yields (entry 8) and in the deposition of a
very thin black film of Pd on the microwave process vial
see below). Note that the use of Pd(Ph P) as phosphine-
3 4
containing homogeneous Pd catalyst as reported by Stelzer
and co-workers did not result in an increased product yield.
Therefore, a self-replicating, ligand-generating catalyst sys-
2
2
Stelzer and co-workers, employ a variety of homogeneous
Pd catalysts, base, and solvent combinations. These reactions
typically furnish moderate to good yields of triarylphosphine
products for iodo precursors, involving 1-72 h of heating
at temperatures of 70-130 °C. The corresponding aryl
(
2
bromides, however, require considerably longer times (125-
2
1
30 °C for 5-7 days). Initially, we tried to adapt these
4
tem does not seem to be in operation here.
protocols to controlled microwave heating conditions in
Interestingly, we discovered that it was also possible to
use heterogeneous Pd sources as catalysts in these transfor-
mations. We are not aware of any literature precedent for
C-P coupling reactions involving secondary phosphines
catalyzed by a heterogeneous transition metal source. To our
surprise, 5% Pd on charcoal (Pd/C) turned out to be a very
effective catalyst for this reaction. Even small amounts of
the catalyst (<1.0 mol % Pd) proved to be effective at 190-
8
closed vessels, using the reported MeCN/Pd(OAc)
2
or DMA/
Pd(Ph P) conditions, in the presence of different bases such
3
4
as KOAc or triethylamine. Our first experiments utilized
iodobenzene and diphenylphosphine as substrates (Scheme
1, X ) I, Z ) H, Ar ) Ph). To our disappointment, we
were unable to obtain reasonable yields of triphenylphosphine
product utilizing either DMA or MeCN as a solvent under
microwave conditions. The yield of triphenylphosphine could
not be raised to >15%, and a number of unidentified
byproducts were present in the reaction mixture under the
high-temperature microwave conditions. After some experi-
mentation with a variety of other solvents (DMF, NMP,
toluene, dioxane), we found that NMP was a very suitable
solvent for this type of transition metal-catalyzed process.
NMP has considerably higher stability than, e.g., DMF, under
2
00 °C in allowing near quantitative conversions to tri-
phenylphosphine within only 2 min (Table 2, entries 3-5).
Presumably, solid Pd/C is absorbing microwave energy very
Table 2. Microwave-Enhanced Synthesis of
Triphenylphosphine from Iodobenzene and Diphenylphosphine
Using Pd/C as a Heterogeneous Catalysta
9
microwave irradiation conditions, absorbs microwave energy
efficiently, and allows product isolation by simply pouring
the reaction mixture into water. Optimized reaction condi-
PhI
5% Pd/C
(mg)
temp
(°C)
time
yield
(%)
entry
(mmol)
(min)
1
2
3
4
5
0.50
0.60
0.75
0.75
0.75
10
10
20
20
20
190
190
190
200
200
3
3
3
3
2
76
93
98
96
96
(
7) For a very recent review, see the following: Larhed, M.; Moberg,
C.; Hallberg, A. Acc. Chem. Res. 2002, 35, 717-727.
8) All microwave irradiation experiments were performed using the
(
SmithSynthesizer from Personal Chemistry AB. For a detailed description
of this instrument, see the following: Stadler, A.; Kappe, C. O. J. Comb.
Chem. 2001, 3, 624-630.
a
(
9) (a) Stadler, A.; Kappe, C. O. Eur. J. Org. Chem. 2001, 925-930.
Reactions were carried in DMF (1.0 mL) with 0.50 mmol of Ph2PH in
the presence of KOAc (0.50 mmol). For details, see Supporting Information.
(
b) Wan, Y.; Alterman, M.; Larhed, M.; Hallberg, A. J. Org. Chem. 2002,
6
7, 6232-6235.
3542
Org. Lett., Vol. 4, No. 20, 2002

2
efficiently and thereby acting as a locally superheated, highly
125-130 °C). While the use of a heterogeneous Pd source
10
active catalyst. Note that here DMF proved to be a superior
solvent to NMP. Evidently, because of the very short reaction
times, the decomposition of DMF resulting in unwanted side-
such as Pd/C produced only trace amounts of triphenylphos-
phine under microwave irradiation conditions, we found that
successful couplings could be achieved employing thermally
stable homogeneous Pd catalysts, such as Herrmann’s
9
reactions is not a problem. After the reaction was completed,
1
2
the triphenylphosphine product could simply be isolated after
filtration from the catalyst and precipitation with water. An
even easier protocol was developed by using a Pd-doped
microwave process vial generated by high-temperature
decomposition of a soluble Pd source (see above). Here the
deposited Pd on the inner glass surface was used as a catalyst,
albeit the catalytic activity was found to be somewhat lower
than that using Pd on charcoal (85% yield of triphenylphos-
phine after 3 min of microwave irradiation to 200 °C).
However, these vials could be reused several times without
loss of catalytic activity, eliminating the necessity of a
filtration step in the workup.11
catalyst. After some optimization work, we found that a
59% isolated yield of pure triphenylphosphine could be
obtained exposing an equimolar mixture of bromobenzene,
diphenylphosphine, and KOAc (0.50 mmol) in DMF (1.0
mL) containing 2 mol % of Herrmann’s palladacycle catalyst
to microwave irradiation at 180 °C for 30 min in a sealed
process vial (see Supporting Information for details).
Finally, we have studied C-P coupling reactions involving
phenyl triflate as a model substrate. Here we have utilized a
combination of a Ni catalyst and a tertiary amine base as
suggested in the literature for related C-P coupling reac-
3
tions. Microwave irradiation for 20 min at 180 °C of a
The above homogeneous and heterogeneous C-P coupling
protocols involving iodobenzene were also applied to a
mixture of diphenylphosphine (0.50 mmol), phenyl triflate
(0.75 mmol), and 1,4-diazabicyclo[2.2.2]octane (DABCO)
(1.00 mmol) in DMF (1.0 mL) containing 2 mol % (ca. 5
number of substituted aryl iodides (Scheme 1: Z ) 2-CO
2
H,
Z ) 2-Br, Z ) 3-OMe, Z ) 2-NH and 1-iodonaphthalene)
2
2
mg) of Ni(dppe)Cl as a catalyst produced a 61% isolated
providing the corresponding functionalized triarylphosphines
in 26-86% yield (Table 3).
yield of pure triphenylphosphine. These conditions compare
most favorably with related triflate-diarylphosphine cou-
plings reported in the literature where long reaction times
and higher equivalents of the base and the Ni catalyst were
3
required.
Table 3. Phosphine Derivatives by Heterogeneous or
Homogeneous Pd Catalysis from Iodobenzene Analogsa,b
In conclusion, we have shown that rapid, direct transition
metal-catalyzed C-P(III) bond formations can be achieved
by microwave dielectric heating, employing a variety of
homogeneous and heterogeneous catalytic systems. We
believe that the observed rate enhancements are due to the
rapid “in core” heating of the reaction mixture due to
significantly higher temperatures of microwave energy and
are not a consequence of a specific (“nonthermal”) micro-
temp time yield
entry
substrate
catalystc (°C) (min) (%)
1
2
3
4
5
1-iodonaphthalene
1-iodo-2-bromobenzene
3-iodoanisol
2-iodoaniline
2-iodobenzoic acid
A
A
B
C
B
180
200
180
180
180
5
10
15
20
10
86
74
34
43
26
13
wave effect. Further work in order to improve the transition
metal catalysts and to achieve higher product yields is in
progress. The application of this high-speed methodology
to access synthetically valuable triarylphosphine ligands in
a
Yields not optimized. b All products were identified on the basis of
c
their MS and NMR data and comparison with literature data. A ) 1.0
mol % Pd/C (5%), B ) 2.0 mol % Pd/C (5%), C ) 3.5 mol % Pd(PPh3)4.
1
4
a combinatorial fashion, involving a broad range of aryl
halide/triflate and secondary phosphine building blocks, is
currently under investigation.
Having established the feasibility of rapid, direct C-P
cross-couplings of aryl iodides with diphenylphosphine, we
were also interested to utilize aryl bromides or triflates in
these processes. Due to the lower reactivity of bromoben-
zenes as compared to iodobenzenes, rather long reaction
times were typically required for the coupling with diphen-
ylphosphine using conventional thermal heating (5-7 days,
Acknowledgment. We thank Personal Chemistry AB
(Uppsala, Sweden) for the use of the Smith Synthesizer.
Supporting Information Available: Full experimental
details for all transformations described. This material is
available free of charge via the Internet at http://pubs.acs.org.
(
10) (a) Whittaker, A. G.; Mingos, D. M. P. J. Chem. Soc., Dalton Trans.
000, 1521-1526. (b) Gabriel, C.; Gabriel, S.; Grant, E. H.; Halstead, B.
S. J.; Mingos, D. M. P. Chem. Soc. ReV. 1998, 27, 213-223.
11) CAUTION! Extreme care must be taken in order to avoid arcing
see ref 10) and destruction of the glass vessel in exposing these metal-
OL026716B
2
(12) Trans-di(µ-acetato)bis[o-(di-o-tolyl-phosphino)benzyl]dipalladium
(II). For details, see the following: Herrmann, W. A.; Bohm, V. P. W.;
Reisinger, C.-P. J. Organomet. Chem. 1999, 576, 23-41.
(
(
doped vials (Figure S1 in Supporting Information) to microwave irradiation.
For the use of Pd-doped porous glass tubing in microwave-assisted C-C
coupling reactions, see the following: Li, J.; Mau, A. W.-H.; Strauss, C.
R. Chem. Commun. 1997, 1275-1276.
(13) For a discussion of specific microwave effects, see: (a) Perreux,
L.; Loupy, A. Tetrahedron 2001, 57, 9199-9223. (b) Kuhnert, N. Angew.
Chem., Int. Ed. 2002, 41, 1863-1866
(14) Kappe, C. O. Curr. Opin. Chem. Biol. 2002, 6, 314-320.
Org. Lett., Vol. 4, No. 20, 2002
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