Dramatic increase of turnover numbers in palladium-catalyzed coupling reactions using high-pressure conditions

Full text of DOI:10.1021/ja952654r

J. Am. Chem. Soc. 1996, 118, 2087-2088
2087
Communications to the Editor
Table 1. Pd-Catalyzed Arylation of 1 at 60 °Ca
Dramatic Increase of Turnover Numbers in
Palladium-Catalyzed Coupling Reactions Using
High-Pressure Conditions
yieldb
(%)
Pd(OAc)2
(mol%)
p
t
rate
(TON/h)
entry
(1a)
2 (1a)
(kbar) (h)
TON
190
-
-
-
-
1
1
1
2
-3
1
10
10
10
10
10
10
10
10
10
8
2
4
12
2
19
25
27
2.2
2.8
2.8
13
61
95
62
22
110
70
23
108
254
g276
211
165
102
g276
178
104
145
g833
-3
-3
-3
-3
-3
†
250
270
220
280
280
1300
6100
Stephan Hillers, Sabrina Sartori, and Oliver Reiser*
c
c
3
4
5
6
(1a)
(1a)
(1a)
(1a)
10
Institut f u¨ r Organische Chemie der
Georg-August-UniVersit a¨ t G o¨ ttingen
Tammannstrasse 2, D-37077 G o¨ ttingen, Germany
-2
-2
10
10
4
12
12
24
-
-
-
-
-
-
2
2
2
3
3
2
7 (1a)
(1a)
10
8
10
10
5 × 10
5 × 10
10
8
8
8
8
2
8
8
8
36 100d
g10000
15200
19800
9800
g10000
6400
ReceiVed August 7, 1995
9 (1a)
0 (1a)
1
72
120
96
76
99
98
e
Palladium-catalyzed coupling reactions of the Heck type have
11 (1a)
2 (1a)
1
developed to become one of the most versatile carbon-carbon
f
-2
-2
-2
-3
-3
bond forming processes.1 Numerous elegant transformations
13 (1a)
10
10
10
36 100
g
1
1
1
1
4 (1a)
36
72
120
64
75
87
in natural and non-natural product synthesis based on palladium
have been developed. However, the lack of reactivity in many
of these reactions often requires high reaction temperatures, long
reaction times, and large amounts of catalysts. While most
palladium-catalyzed C-C-coupling reactions even in the case
of optimized procedures have been reported to proceed with
g
c
5 (1a)
7500
6 (1b)
7 (1c)
5 × 10
8
8
17400
g100000
10
120 100
a
PhI (1 equiv, 2.0 mmol), cycloalkene (3 equiv, 6.0 mmol), NEt
/PPh , 3 mL of 1:1 THF/acetonitrile.
3
(
3 equiv, 6 mmol), 1:2 Pd(OAc)
2
3
b
Combined GC yields of 2, 3, and 4 (2a:3a ≈ 9:1; 2b:3b ≈ 15:1;
2
6
.5-5 mol % of catalyst, using Pd to phosphine ratios of 1:2-
2
c:3c:4c ≈ 8:77:15), using pentamethylbenzene as internal standard.
2
c
d
, quantities of 10-20 mol % often proved to be necessary to
Longer reactions times did not increase the yield. Isolated yield of
3
2a: 71%. Isolated yield of 2a: 69%. f 1:4 Pd(OAc)
6
e
ensure a smooth conversion to the products. There have been
2
/PPh
3
; 2a:3a ≈
:1. g Without PPh
3
; 2a:3a ≈ 28:1.
two successful approaches so far to extend the lifetime of
palladium catalysts, i.e., the use of a large excess of metal-
coordinating ligands such as PPh34 and the use of specially
As a first model system we have chosen the palladium-
catalyzed arylation of 2,3-dihydrofuran (1a).
2
c,d
5
This reaction
designed ligands such as P(o-tolyl)3 which form highly stable
metal complexes.6 We report here a third possibility for
has attracted considerable interest over the past few years since
it offers the possibility of carrying out asymmetric coupling
increasing the lifetime of palladium catalysts, making the use
of excess or specially designed ligands unnecessary.
High pressure has been widely applied in order to activate
addition reactions, cycloadditions in particular. This technique,
however, has received only little attention in transition metal
9
reactions, as well as providing an indirect catalytic approach
1
0
11
to acetate and anti-aldol products.
7
catalysis, mainly to influence the selectivity of a reaction.
Nevertheless, a rate enhancement through pressure in standard
Heck reactions has also been qualitatively observed.8 We report
here that palladium-catalyzed cross-coupling reactions carried
out under pressure (8 kbar) are slightly, but significantly,
accelerated. HoweVer, the decisiVe factor of high pressure is
the increase of lifetime of the catalyst, reflected in its turnoVer
numbers (TON).
Kinetic studies of the phenylation of 1a at 1 bar and 60 °C
indicated that the catalyst, formed in situ from 1:2 palladium-
(
II) acetate/triphenylphosphine, displays an initial activity of
†
Undergraduate exchange student, University of Padova, Italy.
about 100 cycles/h, which subsequently decreases constantly
(e. g., after 6 h the activity had dropped to about 5 cycles/h).
Experiments with 0.1 and 0.01 mol % palladium under normal
pressure (Table 1, entries 1-6) reveal that the maximum TON
for the palladium catalyst are about 250-280. However,
experiments carried out under high pressure clearly show that
the lifetime of the catalyst is dramatically prolonged. While
the maximum catalyst activity is only up to 3 times higher at 8
kbar (entries 7 and 8), catalyst decomposition with time seems
to be very slow, in sharp contrast to the normal pressure
reactions. Thus, reactions carried out at 60 °C on a 2 mmol
(1) Reviews: (a) de Meijere, A.; Meyer, F. E. Angew. Chem. 1994, 106,
2
473-2506; Angew. Chem., Int. Ed. Engl. 1994, 33, 2379. (b) Heck, R. F.
Org. React. (N.Y.) 1983, 27, 1.
2) (a) Heck, R. F. Palladium Reagents in Organic Syntheses; Academic
(
Press Inc.: London, 1985. (b) Jeffery, T. Tetrahedron Lett. 1994, 35, 3051-
4
3
8
. (c) Larock, R. C.; Gong, W. H.; Baker, B. E. Tetrahedron Lett. 1989,
0, 2603-6. (d) Larock, R. C.; Gong, W. H. J. Org. Chem. 1990, 55, 407-
.
(3) (a) Overman, L. E. Pure Appl. Chem. 1994, 66, 1423. (b) Laschat,
S.; Narjes, F.; Overman, L. E. Tetrahedron 1994, 50, 347. (c) Hong, C. Y.;
Overman, L. E. Tetrahedron Lett. 1994, 35, 3453.
(
4) Patel, B. A.; Ziegler, C. B.; Cortese, N. A.; Plevyak, J. E.; Zebovitz,
T. C.; Terpko, M.; Heck, R. F. J. Org. Chem. 1977, 42, 3903.
(
5) Spencer, A. J. Organomet. Chem. 1983, 258, 101-8.
1
2
(
6) Herrmann, W. A.; Brossmer, C.; O¨ fele, K.; Reisinger, C.-P.;
scale at 8 kbar reproducibly gave TON between 10 000 and
Priermeier, T.; Beller, M.; Fischer, H. Angew. Chem. 1995, 107, 1989-92;
Angew. Chem., Int. Ed. Engl. 1995, 34, 1844.
(9) (a) Ozawa, F.; Kubo, A.; Hayashi, T. J. Am. Chem. Soc. 1991, 113,
1419-21. (b) Hayashi, T.; Kubo, A.; Ozawa, F. Pure Appl. Chem. 1992,
64, 421-7. (c) Ozawa, F.; Kubo, A.; Matsumoto, Y.; Hayashi, T.; Nishioka,
E.; Yanagi, K.; Moriguchi, K. Organometallics 1993, 12, 4188-96.
(10) Hillers, S.; Niklaus, A.; Reiser, O. J. Org. Chem. 1993, 58, 3169-
71.
(7) (a) Hillers, S.; Reiser, O. Tetrahedron Lett. 1993, 34, 5265-5268.
(
1
b) Trost, B. M.; Parquette, J. R.; Marquart, A. L. J. Am. Chem. Soc. 1995,
17, 3284-5. (c) Tietze, L. F.; Ott, C.; Gerke, K.; Buback, M. Angew.
Chem. 1993, 105, 1536-8; Angew. Chem., Int. Ed. Engl. 1993, 32, 1485.
d) Yamamoto, Y. In Organic Synthesis at High Pressures; Matsumoto,
K., Acheson, R. M., Eds.; Wiley-Interscience: New York, 1991.
(
(11) Hillers, S.; Reiser, O. Synlett 1995, 153-54.
(
8) (a) Sugihara, T.; Takebayashi, M.; Kaneko, C. Tetrahedron Lett. 1995,
(12) All runs at high pressure were performed several times and were
reproducible within 5%. In Table 1, the lowest yield obtained is always
given.
3
1
6, 5547-50. (b) Voigt, K.; Schick, U.; Meyer, F. E.; de Meijere, A. Synlett
994, 189-90.
0
002-7863/96/1518-2087$12.00/0 © 1996 American Chemical Society

2
088 J. Am. Chem. Soc., Vol. 118, No. 8, 1996
Communications to the Editor
Table 2. Pd-Catalyzed Arylation of 1 at 100 °Ca
Scheme 1
Pd(OAc)
(mol %)
2
p
t
yieldb
(%)
rate
(TON/h)
entry
(kbar)
(h)
TON
-
-
-
4
1
(1a)
(1b)
(1c)
5 × 10
5 × 10
10
8
8
8
8
72
72
168
168
73
67
77
47
146000
134000
770000
470000
2030
1860
4580
2800
4
4
2
3
4
c
-4
(1c)
10
a
For conditions, see footnote a in Table 1. b Combined GC yields
of 2, 3, and 4 (2a:3a ≈ 19:1; 2b:3b ≈ 18:1; 2c:3c:4c ≈ 11:85:4),
c
using pentamethylbenzene as internal standard. 1:12 Pd(OAc)
2
/PPh
3
;
2
c:3c:4c ≈ 10:85:5.
2
0 000 (entries 9-11).13 Moreover, high turnover numbers can
be reached already at a pressure of 2 kbar (entry 12). The
reaction proceeded also in the presence of larger amounts (entry
1
3) and in the absence of any PPh3 (entries 14 and 15), although
steps occurring. A preliminary analysis for the arylation of 1a
is nevertheless given (Scheme 1). Generally, all addition steps
of neutral compounds as well as all dissociation steps in which
slightly lower TON were observed in the latter case. The 2,3-
dihydropyrrole 1b gave equally good results as 1a (entry 16),
while cyclopentene (1c) proved to be even more reactive than
15
ions are formed (electrostriction) might be favored. Moreover,
even decomplexation reactions, e.g., elimination of a palladium
hydride species in 9, should proceed by an associative substitu-
tion mechanism and therefore be favored by pressure.16 Fol-
lowing these principles, pressure should have an activating effect
on all but the intramolecular insertion and migration steps, e.g.,
7 to 9, which are regarded as neutral toward pressure.
This analysis is supported by our finding that the regioiso-
meric ratio 2a:3a is not influenced by pressure at low PPh3
concentrations. Using an excess of PPh3, which acts as a good
nucleophile, substitution of the dihydrofuran ligand in 8 can
successfully compete with the migration pathway. Conse-
quently, under such conditions 3a is found as the main product.7a
In conclusion, we have demonstrated that high pressure might
be used in palladium catalysis as a tool to greatly increase the
lifetime of the catalyst. Further investigations to explore the
effects of high pressure in transition metal catalysis are currently
under way.
1
a or 1b (entry 17).
Increasing the reaction temperature to 100 °C resulted in
considerably higher TON and rates for all substrates, demon-
strating that pressure also stabilizes the catalyst at elevated
temperatures (Table 2). Again, best results were obtained with
a catalyst preformed from 1:2 Pd(OAc)2/PPh3, while larger
phosphine concentrations decreased the reaction rate (cf. entries
3
2
and 4). A pleasant side effect is that the main products 2a,
b, and 3c are formed with better regioselectivity than at the
reaction temperature of 60 °C.
One mode of deactivation of a homogenous palladium-
phosphine catalyst is the dissociation of the stabilizing ligand
from the metal during the reaction followed by precipitation of
palladium from the reaction mixture. This effect is usually
countered by the use of an excess ligand; however, a decrease
of the reaction rate might result in parallel.14 High pressure is
apparently capable of stabilizing the catalyst by strongly
enforcing coordination of even weak ligands such as solvent
molecules to the metal. Ligand/substrate exchange is neverthe-
less still facile, and consequently the catalyst activity is
maintained.
Acknowledgment. We thank the Volkswagenstiftung (AZ 68/870),
the Deutsche Forschungsgemeinschaft (RE 948 1-1), and Fonds der
Chemischen Industrie for their generous support of our work. Helpful
comments of the referees of this manuscript are gratefully acknowledged.
The prediction of the net effect of pressure on a metal-
catalyzed reaction is not easy in light of the multiple reaction
JA952654R
(
13) Addition of the catalyst: 0.05 mmol of Pd(OAc)2 and 0.1 mmol of
(15) le Noble, W. J. Chem. Unserer Zeit 1983, 17, 152-62.
(16) Cf.: (a) van Eldik, R. Angew. Chem. 1986, 98, 671-80; Angew.
Chem., Int. Ed. Engl. 1986, 25, 673. (b) Hallinan, N.; Besancon, V.; Forster,
M.; Elbaze, G.; Duccommun, Y.; Merbach, A. E. Inorg. Chem. 1991, 30,
1112. For a different interpretation, cf. ref 8a.
PPh3 were dissolved in 25 mL of 1:1 THF/acetonitrile, and the appropriate
volume of this catalyst solution was added to the reaction mixture.
(14) Herrmann, W. A.; Brossmer, C.; O¨ fele, K.; Beller, M.; Fischer, H.
J. Organomet. Chem. 1995, 491, C1.