Catalytic solvent-free arsination: First catalytic application of Pd-Ar/As-Ph exchange in the syntheses of functionalized aryl arsines [7]

Full text of DOI:10.1021/ja005875s

8864
J. Am. Chem. Soc. 2001, 123, 8864-8865
exchange reactions from phosphorus to arsenic would provide a
facile synthesis of functionalized arisnes. Such a method would
be a great improvement to the existing methods, which are
difficult and limited in scope.16
Catalytic Solvent-Free Arsination: First Catalytic
Application of Pd-Ar/As-Ph Exchange in the
Syntheses of Functionalized Aryl Arsines
The solvent-free reaction conditions for arsination would add
a further attractive feature to the synthesis. The solventless/solid-
state reactions bear many advantages such as reducing pollution,
low cost, and simplicity in process and handling.17 However, most
of the reported reactions required stoichiometric amount of
catalysts (nonsupported) for the organic transformation.18,19
Herein, we report the first catalytic solvent-free arsination for
the synthesis of functionalized aryl arsines using triphenylarsine
as the reagent by the first catalytic20 application of Pd-Ar/
As-Ph exchange reactions (eq 2).
Fuk Yee Kwong, Chi Wai Lai, and Kin Shing Chan*
Department of Chemistry
The Chinese UniVersity of Hong Kong
Shatin, New Territories, Hong Kong
ReceiVed December 13, 2000
Environmental concerns have brought more awareness into the
development of green chemistry.1 The transformation of an
undesirable side reaction into a synthetically versatile method and
the continuous discovery of solventless reaction system without
the use and disposal of organic solvents constitute two important
areas in green chemistry.
Though no arsination occurred for aryl bromides, the more
reactive aryl triflates were found to undergo catalytic arsinations
in solventless conditions. The methyl ester phenyl triflate 1a was
transformed to the corresponding arsine 1b in 51% isolated yield
in the presence of 10 mol % of Pd(OAc)2 and 2.3 equiv of
triphenylarsine under the solvent-free conditions (Table 1, entry
1). Interestingly, the reaction exhibited a similar rate and yield
of reaction when compared with that carried out in DMF (Table
1, entry 1). The redox-sensitive aryl triflates 2a and 3a which
bear ketone and aldehyde groups, respectively, were transformed
to arsines 2b and 3b directly without complementary protection
and deprotection steps (Table 1, entries 2 and 3). The electron-
withdrawing and reducible nitrophenyl triflate 4a was found to
be compatible in these arsination conditions to give the corre-
sponding arsine 4b (Table 1, entry 4).21 No significant electronic
effect was observed in this arsination since both the electron-
withdrawing cyano group and the electron-donating methoxy
group showed similar rates and yields of reaction (Table 1, entries
5 and 6). The meta-substituted formylphenyl triflate 7a was
transformed to the 3-(diphenylarsino)benzaldehyde (7b) in similar
yield and reaction time when compared with that of para-analogue
3b (Table 1, entries 3 and 7). Moreover, the sterically hindered
ortho-substituted triflates 8a and 9a were converted to ortho-
substituted arsines 8b and 9b in comparable rate of reaction as
their para-substituted triflates (Table 1, entries 5,6 and 8,9).22 The
triflate alternative, nonaflate 10a,23 was converted to the corre-
The undesirable aryl/aryl exchanges between the palladium-
bound Ar′ with phosphorus bound Ar (eq 1) are frequently
observed in the palladium-catalyzed cross-coupling reactions
leading to the formation of scrambled side products.2 The
stoichiometric mechanistic studies of these Pd-Ar/P-Ph ex-
change reactions have been reported by Cheng,3 Novak,4 Grushin,5
and Norton.6 Recently, these undesirable Ar/Ar′ exchange reac-
tions have been utilized in the synthesis of substituted tertiary
phosphines in a catalytic manner.7
Arsines, the arsenic analogue of phosphines, have been reported
to be ligands superior to phosphines in a number of transition
metal-catalyzed organic reactions both in rate acceleration and
product-yield enhancement. Examples include Stille,8 Heck,9
Negishi,10 Suzuki-Miyaura coupling,11 epoxidation,12 cyclization
of an allylic enyne,13 hydroformylation,14 and carbonylation.15 The
extended application of the transition metal-catalyzed aryl-aryl
(1) (a) Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice;
Oxford University Press: New York, 2000. (b) Janssen, F. J. J. G.; van Santen,
R. A. EnVironmental Catalysis; Imperial College Press: London, 1999.
(2) For exchanged product formation in Stille coupling, see: (a) Segelstein,
B. E.; Butler, T. W.; Chenard, B. L. J. Org. Chem. 1995, 60, 12-13. In Suzuki
coupling, see: (b) O’Keefe, D. F.; Dannock, M. C.; Marcuccio, S. M.
Tetrahedron Lett. 1992, 33, 6679-6680. In Heck coupling, see: (c) Hunt, A.
R.; Stewart, S. K.; Whiting, A. Tetrahedron Lett. 1993, 34, 3599-3602. In
C-S coupling, see: (d) Baran˜ano, D.; Hartwig, J. F. J. Am. Chem. Soc. 1995,
117, 2937-2938.
(3) Kong, K.-C.; Cheng, C.-H. J. Am. Chem. Soc. 1991, 113, 6313-6315.
(4) Goodson, F. E.; Wallow, T. I.; Novak, B. M. J. Am. Chem. Soc. 1997,
119, 12441-12453.
(5) Grushin, V. V. Organometallics 2000, 19, 1888-1900.
(6) For Me/Ar exchange, see: Morita, D. K.; Stille, J. K.; Norton, J. R. J.
Am. Chem. Soc. 1995, 117, 8576-8581.
(16) There are no direct synthetic methodologies for functional group
incorporation to arsine ligands. A synthesis of arsine sulfonic acid from aryl
fluoride has been pointed out by a reviewer (Wallow, T. I.; Goodson, F. E.;
Novak, B. M. Organometallics 1996, 15, 3708-3716). The traditional
arsination involved the reaction of organolithium/magnesium reagents with
Ph2AsCl (pyrophoric and not commercially available) or the reaction of aryl
halides with Ph2AsLi/Na (prepared in situ from Ph3As with Li or Na in liquid
NH3), see: (a) Aguiar, A. M.; Archibald, T. G. J. Org. Chem. 1967, 32, 2627-
2628. (b) Ellermann, J.; Dorn, K. Chem. Ber. 1967, 100, 1230-1234. (c)
Reference 9b. To our best knowledge, only the work by Shibasaki on the
catalyzed arsination using Ni(0) and Ph2AsH was reported (pyrophoric and
not commercially available), see: ref 9a.
(7) (a) Kwong, F. Y.; Chan, K. S. Organometallics 2000, 19, 2058-2060.
(b) Kwong, F. Y.; Chan, K. S. Chem. Commun. 2000, 1069-1070.
(8) (a) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585-9595.
(b) Jeanneret, V.; Meerpoel, L.; Vogel, P. Tetrahedron Lett. 1997, 38, 543-
546.
(9) (a) Kojima, A.; Boden, C. D. J.; Shibasaki, M. Tetrahedron Lett. 1997,
38, 3459-3460. For Heck reactions, see: (b) Namyslo, J. C.; Kaufmann, D.
E. Synlett 1999, 114-116.
(17) (a) Tanaka, K.; Toda, F. Chem. ReV. 2000, 100, 1025-1074. (b)
Knochel, P., Ed. Modern SolVents in Organic Synthesis; Springer: New York,
1999; pp 153-207.
(10) (a) Rossi, R.; Bellina, F.; Carpita, A.; Mazzarella, F. Tetrahedron 1996,
52, 4095-4110.
(18) Toda, F.; Tanaka, K.; Iwata, S. J. Org. Chem. 1989, 54, 3007-3009.
(19) For recent catalytic solventless reaction (but which required an Al2O3-
supported catalyst), see: Kabalka, G. W.; Pagni, R. M.; Hair, C. M. Org.
Lett. 1999, 1, 1423-1425.
(11) (a) Johnson, C. R.; Braun, M. P. J. Am. Chem. Soc. 1993, 115, 11014-
11015.
(12) van Vliet, M. C. A.; Arends, I. W. C. E.; Sheldon, R. A. Tetrahedron
Lett. 1999, 40, 5239-5242.
(20) For stoichiometric aryl/aryl exchange reactions of Ph3P, see: refs 3-6.
For reported side reaction and stoichiometric mechanistic study of aryl-aryl
exchange reactions of Ph3As with Pd complexes: see refs 2a and 6,
respectively.
(13) Trost, B. M.; Edstrom, E. D.; Carter-Petillo, M. B. J. Org. Chem.
1989, 54, 4489-4490.
(14) van der Veen, L. A.; Keeven, P. K.; Kamer, P. C.; van Leeuwen, P.
W. N. M. Chem. Commun. 2000, 333-334.
(21) It should be noted that initial experiments showed the nitro group was
reduced to an amino group in the presence of Ph3P/Pd(OAc)2 in the catalytic
phosphination.
(15) Ceccarelli, S.; Piarulli, U.; Gennari, C. J. Org. Chem. 2000, 65, 6254-
6256.
10.1021/ja005875s CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/16/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 36, 2001 8865
Table 1. Palladium-Catalyzed Solvent-Free Arsination of
Scheme 1. Suggested Mechanism for Pd-Catalyzed Arsination
Functionalized Aryl Triflates Using Triphenylarsinea
mixture was heated at 140 °C for 2.5 days. However, only
monosubstituted arsine 1b was detected by GC-MS when the
reaction was heated at 115 °C.
Scheme 1 illustrates a plausible mechanism. Pd(OAc)2 is likely
in situ reduced to Pd(0) by triphenylarsine,27 which subsequently
undergoes oxidative addition with an aryl triflate to yield the aryl-
Pd(II) species (Scheme 1). The Pd-bound aryl ring then undergoes
reductive elimination with AsPh3 to afford the aryltriphenylar-
sonium salt and Pd(0) species, which was supported by the
observed brown solid formation during the course of the reaction
(Scheme 1).28 This arsonium salt intermediate was also isolated
by quenching the reaction and was confirmed by mass spectrom-
etry (see Supporting Information). The substituted arsonium salt
then undergoes As-C oxidative addition to yield the desired
functionalized arsine (Scheme 1). The Pd(0) complex is regener-
ated by the reductive elimination of another equivalent of
triphenylarsine with palladium-bound phenyl group to form the
arsonium triflate coproduct in 70% isolated yield.
In summary, the first catalytic solvent-free Pd-Ar/As-Ph
exchange was reported. The functional group compatible pal-
ladium-catalyzed solventless arsination uses commercially avail-
able, air-stable, and inexpensive triphenylarsine as the arsinating
reagent.29 It was found that the solvent-free reactions have a rate
of reaction comparable to that in solution. Moreover, 9b was
found to be a versatile precursor for the synthesis of a new type
of chiral As,N ligand. Further studies are in progress.
a Reaction conditions: 10 mol % of Pd(OAc)2, 2.3 equiv of Ph3As
and aryl triflate were heated to 115-120 °C under N2. b Isolated yields.
c Results of arsination in DMF in parentheses.
sponding arsine 1b slightly faster than the triflate 1a24 (Table 1,
entries 1 and 10).
The o-cyano arsine 9b was found to be a versatile precursor
for the synthesis of a new type of chiral As,N ligand 11 for
asymmetric catalysis25 (eq 3). Arsine 9b was reacted with (S)-
2-amino-3-methyl-1-butanol in the presence of ZnCl2 catalyst in
chlorobenzene to afford the new type of optically active As,N
ligand 11 in 54% yield (eq 3).26
Acknowledgment. We thank the Research Grants Council of Hong
Kong for financial support (ERB003).
Supporting Information Available: Experimental details, spectral
data of all new compounds, 1b, 1c, 2b-9b, and 11 (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
The double aryl/aryl exchange was observed when the reaction
was heated at elevated temperature (eq 4). The diaryl arsine 1c
was isolated in 13% yield together with 1b when the reaction
JA005875S
(25) For a recent review concerning similar chiral P,N derivatives, see:
Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336-345.
(26) Bolm, C.; Weickhardt, K.; Zehnder, M.; Ranff, T. Chem. Ber. 1991,
124, 1173-1180.
(22) (a) Novak et al. reported that ortho-substituted aryl halides retarded
the rate of aryl-aryl exchange. see: ref 4. (b) Migita et al. reported similar
results which concerned the ortho-substituted aryl halides retarding the rate
of reaction and giving quite low yield of phosphonium salts. Migita, T.; Nagai,
T.; Kiuchi, K.; Kosugi, M. Bull. Chem. Soc. Jpn. 1983, 56, 2869-2870.
(27) Jutand et al. reported the evidences concerning the reduction of
Pd(II) to Pd(0) by triphenylphosphine, but no direct evidence for Pd(II)/Pd-
(0) reduction by triphenylarsine. Amatore, C.; Jutand, A.; M’Barki, M. A.
Organometallics 1992, 11, 3009-3013.
n
(23) Nonaflate ) Nonafluorobutanesulfonate. (a) Niederpru¨m, H.; Voss,
P.; Beyl, V. Liebigs. Ann. Chem. 1973, 20-32. (b) For a review, see: Stang,
P. J.; Hanack, M.; Subramanian, L. R. Synthesis 1982, 85-126.
(24) Knochel et al. reported nonaflate has a 1.4 times faster rate of reaction
compared with that of triflate in zinc-mediated coupling. Rottla¨nder, M.;
Knochel, P. J. Org. Chem. 1998, 63, 203-208.
(28) Grushin, Novak, and Cheng proposed the Pd-Ar/P-Ph exchange
through a phosphonium salt intermediate, see: refs 3-5.
(29) Traditional arsine synthesis involved the reaction of aryl Grignard
reagents with Ph2AsCl, see: ref 16. To our knowledge, no direct synthetic,
functional group tolerable arsination of aryl triflates was reported.