An N-C-N pincer palladium complex as an efficient catalyst precursor for the Heck reaction

Article abstract of DOI:10.1002/adsc.200404161

The Heck reaction of iodobenzene and methyl acrylate took place smoothly in NMP at 140°C in the presence of 1 mol ppb of the pincer palladium complex [4-tert-butyl-2,6-bis{(3R,7aS)-2-phenylhexahydro-1H-pyrrolo[1,2-c] imidazole-1-on-3-yl}-phenyl]chloropall

Full text of DOI:10.1002/adsc.200404161

COMMUNICATIONS
An N-C-N Pincer Palladium Complex as an Efficient Catalyst
Precursor for the Heck Reaction
Kazuhiro Takenaka, Yasuhiro Uozumi*
Institute for Molecular Science (IMS), Higashi-yama, Myodaiji, Okazaki 444-8787, Japan
Fax: (þ81)-564-59-5574, e-mail: uo@ims.ac.jp
Received: June 6, 2004; Accepted: September 17, 2004
Abstract: The Heck reaction of iodobenzene and
methyl acrylate took place smoothly in NMP at
1408C in the presence of 1 mol ppb of the pincer pal-
ladium complex [4-tert-butyl-2,6-bis{(3R,7aS)-2-phe-
nylhexahydro-1H-pyrrolo[1,2-c]imidazole-1-on-3-yl}-
phenyl]chloropalladium to give methyl cinnamate
which corresponds to 520Â106 TON and6500/sec
TOF.
Keywords: aryl halides; cinnamates; Heck reaction;
palladacycle catalyst; pincer complex
The palladium-catalyzed arylation and alkenylation of
olefins, the so-calledHeck reaction, is a versatile syn-
thetic tool for carbon-carbon bondformation. Various
PdII andPd 0 complexes have been investigatedfor use
as catalyst precursors promoting the Heck reaction.
Among the most active ones reportedto date are phos-
phorus-, nitrogen-, andsulfur-containing carbopallada-
cycles[1] with pincer palladium complexes (Figure 1) be-
ing recognizedas one of the most active classes of cata-
lyst precursors for this reaction.[2,3] We report here a new
N-C-N pincer palladium complex 4 which was foundto
promote the Heck reaction of aryl iodides with methyl
acrylate with extraordinarily high catalytic activity, cor-
Figure 1. Representative examples of pincer palladium com-
plexes catalyzing the Heck reaction. Reportedturnover num-
bers (TONs) for the Heck reaction of aryl iodide are given in
parentheses.
responding to a total turnover number (TON) and turn-
over frequency (TOF) of 520Â106 and6500/sec, respec-
tively.
[4-tert-Butyl-2,6-bis{(3R,7aS)-2-phenylhexahydro-1H-
pyrrolo[1,2-c]imidazole-1-on-3-yl}phenyl]chloropalla-
dium (4) is a novel pincer palladium complex having ability of pincer complexes to promote the Heck reac-
hexahydro-1H-pyrrolo[1,2-c]imidazolone groups[4] as tion.
trans-chelating donor groups at the 2,6-positions of the
First, we examinedseveral solvents andbases for the
anionic aromatic ligandmoiety, which we have recently
Heck reaction of iodobenzene (7a) with methyl acrylate
designed and prepared with a view toward use in several (8) in the presence of the pyrroloimidazolone palladium
palladium-catalyzed transformations, including asym- pincer complex 4 (Scheme 2). Representative results
metric catalysis.[5] The pincer complex 4 was readily pre- are summarizedin Table 1. It was foundthat the combi-
paredin high yieldstarting with 4- tert-butyl-2,6-difor- nation of sodium bicarbonate (NaHCO3) as base and1-
mylphenyl trifluoromethanesulfonate (5) via oxidative methyl-2-piperidone (NMP) as solvent is essential to af-
complexation with Pd0 andcondensation with proline
fordefficient reaction conditions for the Heck reaction
anilide, as shown in Scheme 1. As part of our effort to with the pincer catalyst 4. Thus, the reaction of iodoben-
develop their wide utility, we explored the basic catalytic zene (7a) with methyl acrylate (8) was carriedout in
Adv. Synth. Catal. 2004, 346, 1693–1696
DOI: 10.1002/adsc.200404161
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Kazuhiro Takenaka, Yasuhiro Uozumi
COMMUNICATIONS
Table 1. The Heck reaction of iodobenzene (7a) andmethyl
acrylate (8).[a]
[b]
Entry 4 (mol %) Solvent
Base
Yield[%] of 9a
1
0.1
NMP
NMP
NMP
NMP
DMF
NaHCO3 84
NaHCO3 83
NaHCO3 87
2[c] 0.1
3
4
5
6
7
8
9
10
11
0.0001
none
0.1
0.1
2.0
2.0
2.0
2.0
2.0
NaHCO3
–
NaHCO3 19
mesitylene NaHCO3
8
NMP
NMP
NMP
NMP
NMP
Na2CO3 70
K2CO3 76
NaOAc 44
i-Pr2EtN 42
n-Bu3N 19
[a]
[b]
[c]
Scheme 1. Preparation of the pincer palladium complex 4.
All reactions were carriedout at 140 8C for 22 h.
Isolatedyield.
Carriedout in air.
tively, of the Heck product under otherwise similar con-
ditions (entries 10 and 11).
Using the efficient reaction conditions (NMP/
NaHCO3/1408C) identified above, various aryl halides
were examinedfor the Heck reaction with acrylates in
the presence of 1 mol ppm of the pincer palladium com-
plex 4 (Table 2). Thus, the reactions of the ortho-, meta-,
and para-iodotoluenes (7b–d) with 1.2 equivs. of methyl
acrylate (8) were catalyzedby 1.0 mol ppm of the pincer
palladium complex 4 at 1408C in NMP to give 89, 88, and
87% isolatedyields of the Heck products 9b, 9c, and 9d,
i.e., the turnover numbers (TONs) for the palladium cat-
alyst were 888Â103, 882Â103, and873 Â103, respective-
ly (Table 2, entries 1–3). Excellent TONs were also ach-
Scheme 2. The Heck reaction.
NMP in the presence of 1.1 mol equivs. of NaHCO3 and ievedin the reaction of the aryl halides having electron-
0.1 mol % of pincer complex 4 at 1408C for 22 h to give donating as well as electron-withdrawing substituents.
an 84% isolatedyieldof methyl cinnamate ( 9a) (Table 1, The observedTONs in the reactions of para-iodoanisole
entry 1). It is noteworthy that the Heck reaction took (7e), para-chloroiodobenzene (7f), and para-(trifluoro-
place under aerobic conditions to give 83% yield of 9a methyl)iodobenzene (7g) affording 9e, 9f, and 9g were
(entry 2). The reaction of 7a and 8 proceeded smoothly 430Â103, 775Â103, and910 Â103, respectively, to dem-
with only 1 mol ppm of the pincer catalyst 4 under oth- onstrate the wide substituent tolerance of this reaction
erwise similar conditions to give an 87% isolated yield system (entries 4–6). The reactions with naphthyl io-
of the cinnamate 9a (entry 3). The cinnamate 9a was dide (7h) or butyl acrylate (8’) gave the corresponding
not detected by GC-MS analysis at all in the control ex- Heck products 9h or 9a’ in 51 or 60% isolatedyield(en-
periment carriedout without the pincer palladium 4 (en- tries 7 and8).
try 4). The Heck reaction performedin N,N-dimethyl-
formamide (DMF) andmesitylene gave 19% and8%
of the cinnamate 9a, respectively (entries 5 and6),
The high catalytic potential of the pincer palladium
complex 4 promptedus to explore the minimization of
the catalyst loading to promote the Heck reaction. The
whereas the Heck reaction gave 84% yieldof 9a in reaction of iodobenzene (7a) with methyl acrylate (8)
NMP (entry 1). The reaction efficiency is also strongly took place in the presence of 1.0 mol ppb of the pincer
affected by the base employed. Thus, the yields of meth- complex 4 under otherwise similar conditions to give a
yl cinnamate (9a) were lower in the reactions using more 52% isolatedyieldof methyl cinnamate ( 9a) along
basic and less basic inorganic bases, including sodium with 46% of the recoveredstarting aryl substrate with
carbonate, potassium carbonate, andsodium acetate
(Na2CO3: 70%, K2CO3: 76%, NaOAc: 44%) (en- sec were achieved.
which a TON of 519.6Â106 anda TOF of >6500 TOF/
tries 7–9) even with 2 mol % of the pincer complex 4.
Recently, it has been proposedthat palladium nano-
Organic bases such as diisopropylethylamine and tribu- cluster species were generated in situ from PCP pincer
tylamine also gave lower yields, 42% and 19%, respec- palladium complexes to catalyze the Heck reaction
1694
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Adv. Synth. Catal. 2004, 346, 1693–1696

An N-C-N Pincer Palladium Complex
COMMUNICATIONS
Table 2. The Heck reaction of aryl iodides and methyl acry-
are given relative to CDCl3 as an internal standard (d¼77.0).
The 31P NMR data are reported relative to external 85%
H3PO4 . 1H, 13C, and 31P NMR spectra were recorded in
CDCl3 at 258C unless otherwise noted. FAB mass spectra
were recorded on a JEOL JMS-777V spectrometer; 3-nitro-
benzyl alcohol was usedas the matrix. Melting points were de-
terminedusing a Yanaco micro melting point apparatus MP-J3
andare uncorrected. Optical rotations were measuredon a
JASCO P-1020 polarimeter. Commercially available reagents
were usedwithout any purification.
late.[a]
Entry
ArI
Product
Yield [%][b]
TON
1
2
3
4
5
6
7b
7c
7d
7e
7f
7g
7h
7a
9b
9c
9d
9e
9f
9g
9h
9a’
89
88
87
43 (43)
78 (6)
91
51 (37)
60 (30)
888,000
881,700
872,500
430,000
775,000
910,100
506,700
600,000
7
8[c]
4-tert-Butyl-2,6-diformylphenyl
Trifluoromethanesulfonate (5)
[a]
All reactions were carriedout in the presence of the pincer
palladium complex and NaHCO3 at 1408C for 22 h. ArI
(mol)/8 (mol)/[Pd] (mol)/base (mol) ¼1.0/1.2/0.000001/
1.1.
Isolatedyield. SM recovered(%) in parentheses.
n-Butyl acrylate (8’) was usedinsteadof methyl acrylate.
To a solution of 5-tert-butyl-1,3-diformyl-2-hydroxybenzene[9]
(1.72 g, 8.34 mmol) andpyriidne (1.20 mL, 14.8 mmol) in
50 mL of CH2Cl2 was added trifluoromethanesulfonic anhy-
dride (1.80 mL, 10.7 mmol) dropwise at 08C over 10 min.
The reaction mixture was warmedto room temperature and
stirredfor 30 min. The solution was cooledto 0 8C and
quenchedwith 40 mL of 1.5 M HCl. After separation, the
[b]
[c]
aqueous phase was extractedtwice with CH Cl2 (30 mL) and
2
the combinedextract was driedover Na 2SO4. The organic
phase was passedthrough a short plug of silica gel, which was
then washedwith CH 2Cl2 (100 mL). The filtrates were concen-
trated under reduced pressure and the resulting crude solid was
recrystallizedfrom hexane to give the title compoundas a
white crystalline solid; yield: 2.63 g (93%); mp 69–708C. MS
(EI): m/z¼338 ([M]þ); 1H NMR (CDCl3, 500 MHz): d¼1.35
(s, 9H, CH3), 8.22 (s, 2H, ArH), 10.24 (s, 2H, CHO);
13C{1H} NMR (CDCl3, 125 MHz): d¼31.1 [C(CH3)3], 35.5
[C(CH3)3], 118.4 (q, 1JCF ¼320 Hz, O3SCF3), 129.2 (ArC attach-
edto CHO), 132.4 (Ar C), 147.0 (ArC attachedto t-Bu), 153.2
(ArC attachedto OTf), 185.3 ( CHO); anal. calcd. for
C13H13F3O5S: C 46.15, H 3.87, S 9.48; found: C 45.89, H 3.87,
S 9.64.
Scheme 3. The Heck reaction with 1 mol ppb of 4.
with extremely high TON andTOF. [6,7] Although the de-
tailedmechanism of the present Heck reaction with the
NCN pincer 4 is not yet clear,[8] an induction period was
observedin the preliminary kinetic study (time-conver-
sion profile) of the reaction of 7a and 8 to show good
agreement with the profile of the PCP pincer palladium
catalysis.[7]
A novel NCN pincer palladium complex bearing pyr-
roloimidazolone groups was found to catalyze the Heck
reaction with high catalytic activity, i.e., the TON and
the TOF were up to 519.6Â106 and ca. 6500 TOF/sec, re-
spectively. The catalytic efficiency achievedfor the
Heck reaction of various iodoarenes is among the high-
est reportedso far. Mechanistic studies on this catalytic
process are currently underway and will be reported in
due course.
trans-(4-tert-Butyl-2,6-diformylphenyl)chlorobis-
(triphenylphosphine)palladium (6)
4-tert-Butyl-2,6-diformylphenyl trifluoromethanesulfonate (5;
2.03 g, 6.00 mmol), Pd2(dba)3 ·CHCl3 (3.11 g, 3.00 mmol), and
triphenylphosphine (3.15 g, 12.0 mmol) were dissolved in
60 mL of CH2Cl2, which was stirredat room temperature for
4 h. After the solvent was removed, the residue and LiCl
(2.73 g, 64 mmol) were suspended in a mixture of acetone
(50 mL) andwater (10 mL). The reaction mixture was stirred
at room temperature for 10 h andconcentratedunder reduced
pressure. The residue was dissolved in 100 mL of CHCl3, which
was washedwith water (50 mL Â2) andbrine (50 mL), and
dried over Na2SO4. The solvent was removedunder vacuum
andthe resulting solidwas recrystallizedfrom MeCN to afford
6 as yellow crystals; yield: 4.71 g (92%); mp 226–2298C (dec.);
MS (FAB): m/z¼819 ([MÀCl]þ); 1H NMR (CDCl3,
400 MHz): d¼1.16 (s, 9H, CH3), 7.15 (s, 2H, ArH), 7.22 (t,
Experimental Section
General Remarks
All manipulations were carriedout under a nitrogen atmos-
phere unless otherwise noted. Nitrogen gas was dried by pas-
sage through P2O5. NMR spectra were recorded on a JEOL
JNM-AL400 spectrometer (400 MHz for 1H, 100 MHz for
13C, 162 MHz for 31P), JEOL JNM-AL500 spectrometer
3
3
12H, JHH ¼7.6 Hz, m-PhH), 7.30 (t, 6H, JHH ¼7.2 Hz, p-
PhH), 7.50 (dd, 12H, o-PhH), 10.40 (s, 2H, CHO);
13C{1H} NMR (CDCl3, 100 MHz): d¼31.3 [C(CH3)3], 34.1
1
(500 MHz for H, 125 MHz for 13C), or JEOL JNM-LA500
1
spectrometer (500 MHz for H, 125 MHz for 13C). Chemical
2
4
shifts are reportedin d ppm referencedto an internal tetrame-
[C(CH3)3], 127.9 (virtual t, j JCP þ JCP j ¼5.3 Hz, o-PhC),
1 3
thylsilane standard for 1H NMR. Chemical shifts of 13C NMR
129.7 (virtual t, j JCP þ JCP j ¼23.9 Hz, ipso-PhC), 129.9 (p-
Adv. Synth. Catal. 2004, 346, 1693–1696
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Kazuhiro Takenaka, Yasuhiro Uozumi
COMMUNICATIONS
3
5
PhC), 132.4 (ArC), 134.1 (virtual t, j JCP þ JCP j ¼6.3 Hz, m-
Areas, Nos. 412 and 420) for partial financial support of this
work.
PhC), 140.9 (ArC attachedto CHO), 146.7 (Ar C attachedto
2
t-Bu), 172.4 (t, JCP ¼6.2 Hz, ArC attachedto P)d, 194.7
(CHO); 31P{1H} NMR (CDCl3, 162 MHz): d¼22.5 (s); anal.
calcd. for C48H43ClO2P2Pd·CH3CN: C 66.97, H 5.17, N 1.56;
found: C 67.04, H 5.17, N 1.53.
References and Notes
[1] For reviews on palladacycle complexes, see: a) W. A.
Herrmann, V. P. W Bçhm, C.-P. Reisinger, J. Organomet.
Chem. 1999, 576, 23; b) J. Dupont, M. Pfeffer, J. Spencer,
Eur. J. Inorg. Chem. 2001, 1917; c) R. B. Bedford, Chem.
Commun. 2003, 1787.
[4-tert-Butyl-2,6-bis{(3R,7aS)-2-phenylhexahydro-1H-
pyrrolo[1,2-c]imidazole-1-on-3-
yl}phenyl]chloropalladium (4)
[2] For reviews on pincer complexes, see: a) M. Albrecht, G.
van Koten, Angew. Chem. Int. Ed. 2001, 40, 3750;
b) M. E. van der Boom, D. Milstein, Chem. Rev. 2003,
103, 1759; c) J. T. Singleton, Tetrahedron 2003, 59, 1837.
[3] For recent studies on the Heck reaction with pincer cata-
lysts, see: a) I. G. Jung, S. U. Son, K. H. Park, K.-C. Chung,
J. W. Lee, Y. K. Chung, Organometallics 2003, 22, 4715;
b) E. Díez-Barra, J. Guerra, V. Hornillos, S. Merino, J. Te-
jeda, Organometallics 2003, 22, 4610; c) F. Miyazaki, K.
Yamaguchi, M. Shibasaki, Tetrahedron Lett. 1999, 40,
Palladium complex 6 (1.71 g, 2.00 mmol) and l-proline anilide
(3.80 g, 20 mmol) were suspended in 60 mL of MeCN. The sus-
pension was refluxedunder O 2 atmosphere for 94 h (turnedto
a clear solution) andallowedto cool to room temperature. Af-
ter removal of the solvent, the crude product was treated with
MeOH and ether. The resulting yellow powder was filtered,
washed with ether, and dried under vacuum to give 4-Cl; yield:
1.33 g (98%); mp 263–2658C (dec.); MS (FAB): m/z¼639
1
([MÀCl]þ); [a]D24: À161 (c 1.0, CH2Cl2); H NMR (CDCl3,
500 MHz): d¼0.70 (s, 9H, CH3), 1.81 (m, 2H), 2.17 (m, 2H),
2.39 (m, 2H), 2.60 (m, 2H), 3.56 (m, 2H), 4.23 (m, 2H), 5.13
´
7379; d) D. Morales-Morales, R. Redon, C. Yung, C. M.
3
3
(dd, 2H, JHH ¼9.7 Hz, JHH ¼1.9 Hz, bridge-head CH), 5.87
Jensen, Chem. Commun. 2000, 1619; e) M. Ohff, A.
Ohff, M. E. van der Boom, D. Milstein, J. Am. Chem.
Soc. 1997, 119, 11687; f) D. E. Bergbreiter, P. L. Osburn,
Y.-S. Liu, J. Am. Chem. Soc. 1999, 121, 9531; g) A. S.
Gruber, D. Zim, G. Ebeling, A. L. Monteiro, J. Dupont,
Org. Lett. 2000, 2, 1287; h) S. Sjçvall, O. F. Wendt, C. An-
dersson, J. Chem. Soc. Dalton Trans. 2002, 1396; i] M.-H.
Huang, L.-C. Liang, Organometallics 2004, 23, 2813.
[4] a) Y. Uozumi, K. Shibatomi, J. Am. Chem. Soc. 2001, 123,
2919; b) Y. Uozumi, K. Yasoshima, T. Miyachi, S. Nagai,
Tetrahedron Lett. 2001, 42, 411; c) K. Shibatomi, Y. Uozu-
mi, Tetrahedron: Asymmetry 2002, 13, 1769.
3
(s, 2H), 6.15 (s, 2H), 7.20 (d, 4H, JHH ¼7.6 Hz, o-PhH), 7.32
3
3
(t, 2H, JHH ¼7.5 Hz, p-PhH), 7.41 (t, 4H, JHH ¼7.8 Hz, m-
PhH); 13C{1H} NMR (CDCl3, 125 MHz): d¼23.5 (CH2 in pyr-
roloimidazolone ring), 29.2 (CH2 in pyrroloimidazolone
ring), 30.7 [C(CH3)3], 34.2 [C(CH3)3], 63.6 (N-CH2), 71.3
(bridge-head CH), 94.4 (N-CH-N), 121.5 (p-PhC), 126.6 (o-
PhC), 128.0 (ArC), 129.5 (m-PhC), 134.9 (ipso-PhC), 144.6
(ArC attachedto pyrroloimidazolone ring), 146.7 (Ar C attach-
¼
edto t-Bu), 150.0 (ArC attachedto Pd), 170.2 ( C O); anal.
calcd. for C34H37ClN4O2Pd: C 60.45, H 5.52, N 8.29; found: C
60.30, H 5.74, N 8.03.
[5] K. Takenaka, Y. Uozumi, Org. Lett. 2004, 6, 1833–1835.
[6] It has recently been reportedthat palladium nanoparticles
and/or low ligated palladium species are generated in situ
from carbopalladacycle complexes to exhibit the extraor-
dinarily high catalytic performance in the Heck reaction;
see: a) M. Nowotny, U. Hanefeld, H. van Koningsveld, T.
Maschmeyer, Chem. Commun. 2000, 1877; b) I. P. Belet-
skaya, A. N. Karlstedt, A. V. Mitin, A. V. Cheprakov,
G. M. Kazankov, J. Organomet. Chem. 2001, 622, 89;
c) R. B. Bedford, C. S. J. Cazin, M. B. Hursthous, M. E.
Light, K. J. Pike, S. Wimperis, J. Organomet. Chem.
2001, 633, 173; d) C. S. Consorti, M. L. Zanini, S. Leal,
G. Ebeling, J. Dupont, Org. Lett. 2003, 5, 983; e) C. Roca-
boy, J. A. Gladysz, New J. Chem. 2003, 27, 39; f) A. H. M.
de Vries, J. M. C. A. Mulders, J. H. M. Mommers, H. J. W.
Henderickx, J. G. deVries, Org. Lett. 2003, 5, 3285.
General Procedure for the Heck Reactions
To a suspension of NaHCO3 (1.1 equivs.) in NMP (1.0 mL/
1.0 mmol of aryl halide) were added aryl halide (1.0 equiv.),
methyl acrylate (1.2 equivs.) andthe catalyst 4 (as a 0.1 mM sol-
ution in NMP). The reaction mixture was heatedat 140 8C for
22 h andallowedto cool to room temperature. Then the reac-
tion mixture was diluted with water, and the product was ex-
tractedthree times with ether. The combinedextracts were
dried over Na2SO4. The organic phase was concentratedunder
reduced pressure and the crude product was purified by silica
gel column chromatography (eluent: hexane/EtOAc¼100/1),
giving the desired product. CAS Registry numbers of the
Heck products: 9a, 1754-62-7; 9a’, 52392-64-0; 9b, 130451-86-4;
9c, 95416-56-1; 9d, 20754-20-5; 9e, 3901-07-3; 9f, 20754-21-6;
9 g, 20754-22-7; 9 h, 22837-81-6.
[7] M. R. Eberhard, Org. Lett. 2004, 6, 2125.
[8] The Heck reaction of 2,3-dihydrofuran with iodobenzene
in the presence of the chiral pincer complex 4 gave race-
mic mixtures of 2-phenyl-2,3-dihydrofuran and 2-phenyl-
2,5-dihydrofuran. These observations suggest that the ac-
tive palladium species generated in situ may not be coor-
dinated with the chiral pyrroloimidazolone groups.
Acknowledgements
This work was supported by the CREST program, sponsored by
the JST. We also thank the JSPS (Creative Scientific Research,
No. 13GS0024; GRANT-in-AID for Scientific Research, [9] L. F. Lindoy, G. V. Meehan, N. Svenstrup, Synthesis 1998,
No.15205015) and the MEXT(Scientific Research on Priority
1029.
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ꢀ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Adv. Synth. Catal. 2004, 346, 1693–1696