Highly active, stable, catalysts for the Heck reaction; further suggestions on the mechanism

Article abstract of DOI:10.1039/a802642d

Tri(1-naphthyl)phosphine gives palladacycles which are very active catalysts for Heck reactions; mechanisms based on a Pd^II-Pd^IV cycle are proposed and a new, very efficient method of separating the product from the catalyst has been devised, which involves treatment with cyanide ion.

Full text of DOI:10.1039/a802642d

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Highly active, stable, catalysts for the Heck reaction; further suggestions on
the mechanism
Bernard L. Shaw,*† Sarath D. Perera and Elaine A. Staley
School of Chemistry, University of Leeds, Leeds, UK LS2 9JT
Tri(1-naphthyl)phosphine gives palladacycles which are
very active catalysts for Heck reactions; mechanisms based
on a PdII–PdIV cycle are proposed and a new, very efficient
method of separating the product from the catalyst has been
devised, which involves treatment with cyanide ion.
Bromobenzene, a relatively inactive bromide, gave a 77% yield
of stilbene after reacting with styrene at 115 °C for 30 h using
catalyst 2b (entry 7). In entry 8 we used sodium acetate as the
base and the acetylacetonate catalyst 2a. Examples of catalyses
using 3a and 3b are also given. The entries given in Table 1 all
refer to isolated yields of crystalline products. Apart from entry
3, where column chromatography was used, and entry 1, the
products were separated from the palladium catalyst using an
extraction process that we have devised. This depends on the
enormous affinity of palladium for cyanide ion: the formation
constant for [Pd(CN)4]22 is ca. 1052.4 The extraction process
works very well for the examples given in Table 1.‡
The Heck alkenation reaction [eqn. (1)] is very important in
Y
catalyst
solvent
Y
+
BH .
X
base (B)
+
Ar
ArX
+
(1)
organic synthesis with many applications. Frequently, a Heck
catalyst has been generated in situ from Pd(OAc)2 and a tertiary
phosphine, L = PPh3 or P(C6H4Me-o)3. This is assumed to give
some PdL2, which forms part of a catalytic cycle involving Pd0–
PdII. Recently, highly efficient catalysts using cyclopalladated
P(C6H4Me-o)3 have been reported.1a,b One of us has suggested
a quite new mechanism for such catalyses with reversible
nucleophilic attack on PdII-coordinated alkene being a key step
in the promotion of oxidative addition of ArX, in a PdII–
PdIV catalytic cycle.2 Previously, as part of an extensive study
on the effects of steric compression, we found that 1-naph-
thylphosphines could give particularly stable metallacycles,3
with metallation in the 8- or peri-position. We have now found
tri(1-naphthyl)phosphine (PNp3) cyclopalladates to give very
stable palladacycles, which are excellent catalysts for Heck
reactions.
On heating PNp3 with Pd(OAc)2 in toluene the metallacycle
1a was obtained. 1a showed broad NMR spectra at 25 °C,
probably due to exchange at the bridging acetates; the spectra
sharpened at 260 °C. Broad NMR spectra were similarly found
for the palladacycles prepared from Pd(OAc)2 and P(C6H4Me-
o)3.1a We treated 1a with acetylacetone and converted it into the
mononuclear acetylacetonate 2a which showed sharp NMR
spectra at 25 °C. 2a can be more conveniently made by treating
[Pd(acac)2] with PNp3 in hot benzene. 2b was similarly
prepared from PNp3 and [Pd(hfacac)2]. We have similarly
cyclopalladated P(C6H4Me-o)3 to give 3a and 3b. All these new
palladacycles have been fully characterised.
We suggest a mechanism for the Heck reactions catalysed by
1a, 2a or 2b which is analogous to that proposed by one of us2
for Heck reactions. The mechanism involves PdII–PdIV, with
the alkene coordinating to the PdII being reversibly attacked by
a nucleophile, such as OAc2, acac2, OH2, Br2 or I2, to give a
negatively charged alkyl species 5 in which the PdII is electron
rich and oxidatively adds ArX. Loss of nucleophile regenerates
the coordinated alkene and migration of Ar from PdIV to
coordinated alkene followed by b-hydrogen migration, gives
the product ArCHNCHY and removal of HBr by the base
regenerates the PdII catalyst of type 1, (see Scheme 1).
R1
PR2
X
X
PR2
Pd
O
O
Pd
Pd
R2P
R1
2a R = naphthyl, R1 = Me
2b R = naphthyl, R1 = CF3
1a R = naphthyl, X = OAc
1b R = naphthyl, X = I
1c R = naphthyl, X = Br
R1
R2
P
O
O
Pd
C
H2
R1
3a R = o-tolyl, R1 = Me
3b R = o-tolyl, R1 = CF3
The palladacycles 1a, 2a and 2b are excellent catalysts for
Heck reactions. Some of our catalytic results are summarised in
Table 1. Thus treatment of iodobenzene with styrene at 120 °C
for 5 days using 1024 mol% catalyst 2b gave stilbene in 65%
isolated yield, i.e. a turn over number (TON) of 650 000. No
palladium metal was formed and the final reaction solution was
extremely pale yellow. Treatment of iodobenzene with methyl
acrylate at 95 °C for 13 days using 5 3 1025 mol% of catalyst
2b gave methyl cinnamate with a TON of 1 120 000, the highest
turnover number yet reported for a Heck reaction; with 1023
mol% catalyst reacting at 95 °C for 5 d we isolated methyl
cinnamate in 88% yield with a TON of 88 000. Herrmann and
Beller’s catalysts gave TONs of up to 100 000, or in the
presence of much NBu4Br as promoter, 1 000 000; NBu4Br is
expensive and we tried to achieve high TONs without it.
4-Bromoacetophenone reacted with styrene at 125 °C over 7 h
to give 4-acetylstilbene in 94% isolated yield using catalyst 1a
(entry 5); similarly with 4-bromocyanobenzene (entry 6).
2–
n–
Y
H
Y
Y
H
H
H2
C
H2
C
L
L
Pd
Pd
X
X
C
H2
C
H2
Y
H
2
11a X = OC(=O)O
11b X = O
10a X = OC(=O)O
10b X = O
–
Y
Y
H
H
H2
C
PR2
Pd
PR2
Pd
O
X
C
H2
PR2
12
13
Chem. Commun., 1998
1361

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Table 1 Selected results of the Heck reactions catalysed by palladium chelatesa
ArX/alkene
mmol/mmol
Entry
Aryl halideb Alkene
Catalyst/mmol
Time (T/°C)
Yield (%) (TON)
1
2
3
4
5
6
7
8
9
PhI
PhI
PhI
PhI
bab
bcb
PhBr
PhI
PhI
PhI
PhI
sty
sty
mac
mac
sty
sty
sty
sty
sty
10/12.5
10/12.5
10/10
10/10
2/2.6
2/3
10/12.5
2/2.2
2b (1025
2b (1023
)
)
5 d (120)
17 h (95)
13 d (95)
5 d (95)
7 h (125)
7 h (125)
30 h (115)
24 h (95)
8 h (95)
65 (650 000)
78 (7800)
56 (1 120 000)
88 (88 000)
94 (180)
85 (165)
77 (770)
56 (115)
83 (240)
2b (5 3 1026
)
2b (1024
)
1a (5.2 3 1023
1a (5.2 3 1023
)
)
2b (1022
)
2a (1022
3a (7 3 1023
3b (1022
2a (1.9 3 1023
)
2/3
10/12.5
2/2.2
)
10
11
sty
mac
)
4 h (95)
24 h (95)
90 (900)
72 (760)
)
a Except for entry 8, an equivalent amount of tri-(n-butyl)amine to the aryl halide was used as base; in entry 8, 4 mmol of sodium acetate was used. The catalyst
b
was dissolved in dmf, e.g. 1 cm3 in entry 1. Experimental details available upon request from the authors. bab = 4-bromoacetylbenzene, bcb =
4-bromocyanobenzene, sty = styrene, mac = methyl acrylate.
In the so-called exceptionally mild ‘Jeffrey’ conditions for
effecting a Heck reaction, viz [Pd(OAc)2], an aryl iodide and an
alkene such as CH2NCHY reacting in dmf at ca. 30 °C in the
presence of sodium hydrogen carbonate or potassium carbonate,
with much added NBu4Cl as phase-transfer catalyst, very good
yields are obtained. One of us suggested that the remarkable
ability of aryl iodide to oxidatively add to PdII at such as low
species from palladacycles. Because of the beneficial effect of
water we deliberately did not dry our reagents nor the dmf
solvent (!0.1% water). Electron rich ‘ate’ complexes of iron(ii)
or cobalt(ii) e.g. [FeMe4]22 or [CoMe4]22, react with a series of
vinyl bromides, such as b-bromostyrene, even at 278 °C,
undergoing oxidative addition/reductive elimination:6 ‘ate’
complexes of PdII, NiII and PtIV are known. We also suggest that
attack on two-coordinated alkenes by H2O + base could give 12,
as an electron rich PdII complex which oxidatively adds ArX
and which could participate in a catalytic cycle similar to that
shown in Scheme 1. Recently, the very stable and sterically
hindered chelates of type 13 have been shown to be very stable
catalysts for Heck reactions giving very high TON but requiring
high reaction temperatures (140 °C) even with iodides.7 We
suggest a mechanism similar to that shown in Scheme 1 for
catalyses by 13.
2
22
temperature arises because HCO3 or CO3
attacks two
coordinated alkenes to give chelated dialkyl species 10a and
11a, X = CO3.2 11a is an ‘ate’ complex with an extremely
electron-rich palladium. We now suggest that under these
conditions the bridging group X could be an oxygen atom,
formed from water + base attacking two coordinated alkenes,
i.e. 10b and 11b. Water is known to promote Heck reactions
including under Jeffrey conditions.5 We suggest that one
function of the large cations such as NBu4+ is to help stabilise
in solution large anions such as of type 10 or 11 and analogous
Notes and References
nuc
nuc
Ar
† E-mail: b.l.shaw@chem.leeds.ac.uk
‡ For entry 5 the reaction mixture was dissolved in CH2Cl2 (10 cm3) and the
organic layer washed successively with water, with a solution of NaCN (2
mg) in water (5 cm3), with 2 m HCl, and finally with water; evaporation and
crystallisation from MeOH gave the product;. similarly for the other entries.
For syntheses involving methyl acrylate, diethyl ether was used in the work
up. Preliminary work suggests that the treatment with NaCN gives a little
PNp3 but the main product seems to be a rapidly interconverting mixture of
–
–
P
C
P
C
P
C
iii
ii
Y
Y
Pd
Pd
Pd
Y
Br
Br
Br
i
Br
4
5
6
1c
sodium salts of type [Na+]n[Np2PC10H6Pd(CN)n+1 n2 which is not soluble
]
vii
P
in CH2Cl2 or Et2O, is very soluble in MeOH and presumbably sufficiently
soluble in dilute aqueous NaCN; very small quantities are involved,
typically mg of Pd.
iv
H
Ar
Pd
vi
Y
Ar
Pd
Br
Br
C
P
1 (a) W. A. Herrmann, C. Brossmer, C.-P. Reisinger, T. H. Riermeier, K.
P
C
v
Y
¨
Pd
Br
Br
Ofele and M. Beller, Chem. Eur. J., 1997, 3, 1357; (b) M. Beller and
Y
Br
T. H. Riermeier, Eur. J. Inorg. Chem., 1998, 1, 29.
2 B. L. Shaw, New J. Chem., 1998, 77.
Br
9
C
Ar
3 J. M. Duff and B. L. Shaw, J. Chem. Soc., Dalton Trans., 1972, 2219.
4 M. T. Beck, Pure Appl. Chem., 1987, 59, 1703.
5 T. Jeffery, Tetrahedron Lett., 1994, 35, 3051 and references therein.
6 T. Kauffmann, B. Laarmann, D. Menges and G. Neiteler, Chem. Ber.,
1992, 125, 163.
7
8
Scheme 1 Proposed mechanism for the Alkenation reaction using a
palladacycle of type 1 or 2 and an aryl bromide. After several cycles the
bromide 1c will be formed and is used in the Scheme. i, CH2NCHY; ii,
reversible attack by nucleophile (OAc2, Br2, acac2 or OH2); attack is
shown on the terminal carbon atom but it could be on the internal carbon;
iii, oxidative addition of ArBr; iv, loss of nucleophile; v, migration of Ar to
terminal carbon; vi, b-hydrogen elimination; vii, removal of HBr by base.
7 M. Ohff, A. Ohff, M. E. van der Boom and D. Milstein, J. Am. Chem.
Soc., 1997, 119, 11 687.
Received in Cambridge, UK, 7th April 1998; 8/02642D
1362
Chem. Commun., 1998