Highly active Pd(II) cyclometallated imine catalysts for the Heck reaction

Article abstract of DOI:10.1039/a809883b

The new cyclopalladated, phosphine-free imine complexes 1-3 are exceptional catalysts for the Heck arylation, leading to more than a million turnovers in some cases; the catalysts are very thermally and air stable and are recovered unchanged after the catalysis.

Full text of DOI:10.1039/a809883b

Highly active PdII cyclometallated imine catalysts for the Heck reaction
Manuela Ohff, Andreas Ohff and David Milstein*
Department of Organic Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel.
E-mail: comilst@wiccmail.weizmann.ac.il
Received (in Cambridge, UK) 18th December 1998, Accepted 14th January 1999
The new cyclopalladated, phosphine-free imine complexes
1–3 are exceptional catalysts for the Heck arylation, leading
to more than a million turnovers in some cases; the catalysts
are very thermally and air stable and are recovered
unchanged after the catalysis.
upon addition of more substrates catalysis is resumed. At the
end of the catalysis, the acetate or trifluoroacetate moieties are
substituted to give the corresponding palladiumhalide complex.
Conveniently, catalyst 1 can be formed in situ under the reaction
conditions from Pd(OAc)2 and the readily available imine
ligand, leading to similar results.
The Heck arylation of alkenes [eqn. (1)] is a useful synthetic
method that is attracting much current interest.1 Normally,
palladium phosphine complexes are utilized, and the reactions
While very high TONs and yields are observed for catalysts
1–3, complex 1 exhibits higher turnover rates. Of the solvents
tested, N-methylpyrrolidone (NMP) was found to be the best.
The reaction can be carried out also in solvents of lower polarity
(dioxane) or non-polar ones (mesitylene), although at lower
rates. Pure solvent and starting materials should be used in the
highly catalytic reactions. Both Na2CO3 and NEt3 were used as
bases, although the reaction was faster with the soluble amine,
leading to a turnover rate of ca. 8 3 104 h21 and 100% yield
with iodobenzene and methyl acrylate.
In a typical experiment, a slight excess of the olefin is added
to a solution of the aryl halide in freshly distilled NMP,
followed by addition of an equimolar amount of NaHCO3 or
NEt3. The catalyst is added and the mixture is stirred at 140 °C
for the specified time. The reaction mixture is analyzed by gas
chromatography and is worked up by addition of water and
extraction of the organic phase with CH2Cl2. After evaporation
of the volatiles, the essentially pure product is characterized by
NMR and IR spectroscopy. Selected results are listed in Table
1.
are conducted under an inert atmosphere. Recently, very
efficient catalysis using palladium complexes incorporating
cyclometallated phosphines,2,3 chelating diphosphines,4 car-
bene ligands5 and dimethylglycine6† have been reported. We
have reported that palladium complexes of tridentate PCP-type
ligands are excellent catalysts, and have provided evidence
which renders the traditional Pd0/PdII cycle unlikely in that
case.6 The issue of a possible PdII/PdIV cycle in Heck catalysis
is currently under debate.4,7,8 and a new mechanism involving
PdIV intermediacy in Heck catalysis has been suggested.9
We report here10 that the palladium imine complexes 1–3 are
outstanding catalysts for this reaction with turnover numbers
As expected, the reaction outcome depends on the halide and
on the olefin. With iodobenzene and methyl acrylate, essentially
complete conversions are obtained with very high turnover
numbers of up to 1.4 3 106, which are among the highest
observed so far.∑ Methyl crotonate and styrene also react
normally, while significantly lower rates are obtained with non-
activated alkenes. Chlorobenzene was only marginally re-
active.13** The observed TON of 137 100 in the case of
bromobenzene is similar to the one that we reported for PCP-
type ligands6 but the reaction was slower in the latter case. As
(TON) of more than 106 in some cases. These readily prepared
PdII catalysts are exceedingly thermally stable and are not
sensitive to oxygen. The use of phosphine free, nitrogen-based
ligands in the Heck reaction is very rare and was reported for
bidentate nitrogen ligands. However, low catalytic activity was
observed.11‡
The new dimeric imine complexes 1–3 in which the metal
center is stabilized by a five-membered ring, were readily
prepared by treatment of Pd(O2CCF3)2 or Pd(OAc)2 with the
corresponding imines in THF.§ Complex 1 was characterized
by X-ray analysis (Fig. 1).¶ X-Ray structures of other palladated
imine complexes were reported.12
Complexes 1–3 show extremely high activity in the catalytic
arylation of olefins with aryl iodides and bromides (Table 1).
Because of the stabilizing metallated ligand system, the
complexes are very thermally stable and no degradation is
observed under the reaction temperatures. These complexes are
also not sensitive to oxygen and moisture and the reactions can
be carried out in air, with no change in efficiencies or yield. The
catalyst remains highly active after the reaction is complete, and
Fig. 1 Perspective view (ORTEP) of complex 1. Bond distances (Å) and
angles (°) (errors in last digits in parentheses) are: Pd(1)–C(100) 1.942(6);
Pd(1)–N(1) 2.035; Pd(1)–O(11) 2.065(5); Pd(1)–O(20) 2.174(4); N(1)–
C(106) 1.295(8); C(100)–C(105) 1.422(9); C(105)–C(106) 1.450(9);
C(100)–Pd(1)–N(1) 81.0(2); C(100)–Pd(1)–O(11) 92.7(2); C(100)–Pd(1)–
O(20) 178.3(2).
Chem. Commun., 1999, 357–358
357

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Table 1 Results of the Heck reaction with the imine catalyst 1–3
Catalysts
(mmol/1025
ArXa
Alkenea
Solventb
Base
)
t/h
T/°C
TON
Yield (%)c
PhI
PhI
PhI
PhI
PhI
PhI
PhI
PhI
methyl acrylate
methyl acrylate
methyl acrylate
methyl acrylate
methyl acrylate
methyl acrylate
methyl acrylate
methyl acrylate
styrene
methyl crotonate
methyl acrylate
methyl acrylate
methyl acrylate
methyl acrylate
methyl acrylate
dihydropyran
indene
NMP
Dioxane
NMP
DMA
Dioxane
Mesitylene
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
Na2CO3
Na2CO3
NEt3
NEt3
NEt3
NEt3
Na2CO3
NEt3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
NEt3
1 (3.5)
1 (3.5)
1 (3.5)
1 (3.5)
1 (3.5)
1 (3.5)
1 (0.46)
1 (0.35)
1 (3.5)
1 (3.5)
1 (3.5)
1 (3.5)
1 (3.5)
2 (3.5)
3 (3.5)
3 (70)
3 (70)
3 (70)
3 (70)
3 (10.5)
2 (7.0)
b
9
40
1
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
120
120
120
140
120
140
142900
36900
142900
93700
100d
25d
100d
66d
75d
93d
100d
100d
74e
16
16
16
32
18
80
39
12
43
25
22
22
68
115
68
22
24
130
107200
130300
1087000
1429000
105700
140000
138600
137100
140000
142900
142900
4300
PhI
PhI
98f
4-MeO-C6H4I
PhBr
4-CHO-C6H4I
97g
96d
98h
100d
100d
60i
PhI
PhI
PhI
PhI
PhI
PhI
PhI
PhBr
5100
3000
7100
38100
72j
cyclohexene
42i
dihydrofuran
dihydrofuran
methyl acrylate
100i
80i
NMP
NMP
Na2CO3
132900
93d
a
c
Amounts: ArX, 5 mmol; alkene, 6 mmol; Na2CO3, 3.5 mmol; NEt3 7 mmol. NMP = N-methylpyrrolidone; DMA = N,N-dimethylacetamide.
Determined by GC, based on the aryl halide. Methyl trans-cinnamate. Stilbene, cis:trans = 1:7. Methyl trans-3-methylcinnamate:methyl cis-
3-methylcinnamate:3-methylenebenzenepropanoic acid methyl ester:methyl 4-phenylbut-2-enoate (10:1:1:1). Methyl trans-p-methoxycinnamate.
h Methyl trans-p-formylcinnamate. i Mixture of isomers of the phenyl derivatives of the olefins.j Mixture of isomers, main product: 2-phenylindene.
d
e
f
g
182/1144. Crystallographic data are available in .cif format from the RSC
far as we are aware, our results with the relatively inactive
web site, see: http://www.rsc.org/suppdata/cc/1999/357
∑ As far as we are aware, this is the highest TON reported for a quantitative
Heck reaction. A TON of 1120000 was reported for the reaction of
In summary, the metallated imine palladium(ii) complexes
iodobenzene with methyl acrylate after 13 days at 95 °C, but the yield was
show exceedingly high catalytic activity and yields in the Heck
56%. See ref. 3.
bromobenzene and the commonly used acrylate esters are
unsurpassed.
reaction, including reactions of the non-activated bromo-
** Catalysis with chlorobenzene was accomplished by addition of NaI and
benzene. The activities observed are among the highest reported
for the Heck reaction. The new catalyst system is very thermally
and air stable. Further investigations aimed at clarification of
the scope and mechanism of these reactions are in progress.
We thank Dr L. J. W. Shimon for the X-ray analysis of
complex 1. This work was supported by The Israel Science
Foundation, Jerusalem, Israel, and by the MINERVA Founda-
tion, Munich, Germany. M. O. thanks the Deutsche For-
schungsgemeinschaft for a fellowship. A. O. thanks the
Minerva Foundation for a fellowship. D. M. is the holder of the
Israel Matz Professorial Chair of Organic Chemistry.
NiBr2. However, the reaction was very slow, resulting in 10% yield and 190
TON after 21 h at 140 °C.
1 Reviews: R. F. Heck, Palladium Reagents in Organic Synthesis,
Academic Press, London, 1985; R. F. Heck, Comprehensive Organic
Synthesis, ed. B. M. Trost and I. Flemming, Pergamon, Oxford, New
York, 1991, vol. 4, p. 833; V. V. Grushin and H. Alper, Chem. Rev.,
1994, 94, 1047; A. de Meijere and F. E. Meyer, Angew. Chem., Int. Ed.
Engl., 1994, 33, 2379; W. Carbri and I. Candiani, Acc. Chem. Res.,
1995, 28, 2.
¨
2 W. A. Herrmann, C. Brossmer, K. Ofele, C.-P. Reisinger, T. Riermeier,
M. Beller and H. Fisher, Angew. Chem., Int. Ed. Engl., 1995, 34, 1844;
M. Beller, T. H. Riermeier, S. Haber, H.-J. Kleiner and W. A. Herrmann,
Chem. Ber., 1996, 129, 1259; W. A. Herrmann, C. Brossmer, C.-P.
Notes and references
¨
Reisinger, T. H. Riermeier, K. Ofele and M. Beller, Chem. Eur. J., 1997,
3, 1357.
† The role of the dimethylglycine additive is unclear and stabilized
palladium colloids may be involved in this case. See ref. 6.
3 B. L. Shaw, S. D. Perera and E. A. Staley, Chem. Commun., 1998,
1361.
4 B. L. Shaw and S. D. Perera, Chem. Commun., 1998, 1863.
5 W. A. Herrmann, M. Elison, J. Fischer, C. Ko¨cher and G. R. J. Artus,
Angew. Chem., Int. Ed. Engl., 1995, 34, 2371.
6 M. T. Reetz, E. Westermann, R. Lohmer and G. Lohmer, Tetrahedron
Lett., 1998, 39, 8449.
7 M. Ohff, A. Ohff, M. E. van der Boom and D. Milstein, J. Am. Chem.
Soc., 1997, 119, 11687.
8 M. Beller and T. H. Riermeier, Eur. J. Inorg. Chem., 1998, 1, 29.
9 B. L. Shaw, New. J. Chem., 1998, 22, 77.
10 M. Ohff, A. Ohff and D.Milstein, Israel Patent Appl., 121346 (filed on
20.07.1997).
11 W. Cabri, I. Candiani, A. Bedeschi and R. Santi, Synlett, 1992, 871.
12 For example, G. Zhao, Q. G. Wang and T. C. Mak, J. Chem. Soc.,
Dalton Trans., 1998, 1241.
13 For high yield Heck reactions with chlorobenzene and other unactivated
aryl chlorides, see Y. Ben-David, M. Portnoy, M. Gozin and D.
Milstein, Organometallics, 1992, 11, 1995; M. Portnoy, Y. Ben-David
and D. Milstein, Organometallics, 1993, 12, 4734; M. T. Reetz, G.
Lohmer and R. Schwickardi, Angew. Chem., Int. Ed., 1998, 37, 481.
‡ With phenanthroline ligands, only 40 TON or less were obtained.
Bipyridine and bis-oxazoline ligands were inactive with methyl acrylate and
resulted in very low yields and turnovers with other alkenes. See ref. 11.
3
§ 1: dH(C6D6) 0.85, 1.15 (d, JHH 6.6, 3H, CH3), 1.06 (s, 3H, CH3), 3.20
3
(sept, JHH 6.6, 1H, CH), 6.46, 7.29 (m, 1H, Haryl), 6.77 (m, 2H, Haryl);
dc(C6D6) 14.0, 20.8, 21.9, 54.4 (s, CH/CH3), 116.8 (q, JCF 288, CF3), 124.3,
126.7, 129.6, 132.5 (s, Caryl), 166.0 (q, 2JCF 38, OCNO), 179.2 (s, CNN). For
2: dH(C6D6) 2.22 (s, 3H, CH3), 2.62, 2.82, 3.00, 3.24 (m, 1H, CH2), 6.71,
6.84 (m, 3JHH 7.6/7.4, 1H, Haryl), 7.01 (d, 3JHH 7.4, 1H, Haryl), 7.48 (d, 3JHH
7.6, 1H, Haryl); dC(C6D6) 24.5 (s, CH3), 49.6, 69.7 (s, CH2), 123.4, 125.1,
130.1, 132.1, 131.8, 149.2 (s, Caryl), 174.4 (s, CNN), 181.1 (s, OCNO). For
3: dH(C6D6) 0.70 (d, 3JHH 6.6, 6H, CH3), 0.84 (m, 1H, left part of CH2), 1.14
(m, 1H, CH), 1.82 (ddd, 1H, right part of CH2), 2.16 (s, 3H, CH3), 3.09 (m,
3
1H, CH), 3.37 (m, 2H, CH2), 6.75 (t, JHH 7.6, 1H, Haryl), 6.87, 7.13 (m,
3JHH 7.6, 1H, Haryl), 7.50 (d, 3JHH 7.6, 1H, Haryl); dC(C6D6) 21.8, 23.5, 24.6,
25.2 (s, CH/CH3), 43.5, 75.5 (s, CH2), 60.4 (s, CH), 123.5, 125.2, 130.2,
132.0, 132.4, 149.3 (s, Caryl), 173.2 (s, CNN), 181.1 (s, OCNO).
¶ Crystal data for 1: C26H28N2O4F6Pd2, M = 759.30, yellow, plates, 0.2 3
0.2 3 0.05 mm3, monoclinic, P2(1)/c (No. 14), a = 17.044(3), b =
16.976(3), c = 19.725(4) Å, b = 97.75° (3), from 25 reflections, T = 110
K, V = 5655(2) Å3, Z = 8, Dc = 1.784 Mg m23, m = 1.346 mm21, Mo-Ka,
12993 independent reflections, Rint = 0.0481, final R1 = 0.0618. CCDC
Communication 8/09883B
358
Chem. Commun., 1999, 357–358