Palladium(II)-N-heterocyclic carbene complexes derived from proline: Synthesis and characterization

Article abstract of DOI:10.1016/j.tet.2010.08.021

Pd(II)-N-heterocyclic carbene complexes derived from proline have been successfully synthesized in good yields and their structures have been characterized by X-ray single crystal diffraction. It was found that the substituents on the N-atom of the pyrrolidine skeleton dramatically affect on the coordination pattern of the palladium complexes. In a word, when an electron-rich group as benzyl group was attached on the N-atom, both of the N-atom and NHC were coordinated to the Pd(II) center; while when an electron-poor group as Ts group was attached, a dimeric mono-coordinated Pd(II)-NHC was obtained exclusively.

Full text of DOI:10.1016/j.tet.2010.08.021

Tetrahedron 66 (2010) 7970e7974
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium(II)eN-heterocyclic carbene complexes derived from proline:
synthesis and characterization
*
Yi-Qiang Tang, Jian-Mei Lu, Xiu-Ren Wang, Li-Xiong Shao
College of Chemistry and Materials Engineering, Wenzhou University, Chashan University Town, Wenzhou, Zhejiang Province 325035, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 May 2010
Received in revised form 23 July 2010
Accepted 10 August 2010
Available online 13 August 2010
Pd(II)eN-heterocyclic carbene complexes derived from proline have been successfully synthesized in
good yields and their structures have been characterized by X-ray single crystal diffraction. It was found
that the substituents on the N-atom of the pyrrolidine skeleton dramatically affect on the coordination
pattern of the palladium complexes. In a word, when an electron-rich group as benzyl group was at-
tached on the N-atom, both of the N-atom and NHC were coordinated to the Pd(II) center; while when an
electron-poor group as Ts group was attached, a dimeric mono-coordinated Pd(II)eNHC was obtained
exclusively.
Keywords:
Proline
N-Heterocyclic carbene
Palladium complex
Characterization
Electronic effect
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
with LiAlH4.7 Replacement of the hydroxy group in prolinol 2 with
Br atom was accomplished in 76% yield by using the combination of
Sincethe isolationof thefirststablefreecarbenebyArduengoetal.
in 1991,1 the chemistry of carbene and their transitionemetal com-
plexes have been dramatically concerned during the past years.2
Development of donor-functionalized N-heterocyclic carbene
(NHC)emetal complexes has been attracted much attention and it
was found that these bifunctional carbeneemetal complexes will
enhance catalytic activity in carbonecarbon and carboneheteroatom
bond formations.3 Although some skeletons of these carbene
have been documented,4 less attention was paid on the palla-
diumecarbene complexes based onproline.5 In this paper, we wish to
report our results on the first synthesis and structure determination
of Pd(II)eNHC complexes derived from proline.
PPh3 and CBr4.8 Finally, reactions of the bromide 3 with N-methyl or
-ethyl imidazole gave the target imidazolium salts 4a and 4b in 98%
and 96% yields, respectively (Scheme 1).
(a)
(b)
OH
COOH
COOH
N
N
N
H
1
Ph
2
Ph
N
R
(c)
(d)
Br
N
N
N
Br
4a: R = Me, 98%
Ph
Ph
3
2. Results and discussion
2.1. Synthesis of ligands
4b: R = Et, 96%
Scheme 1. Synthesis of proline-based imidazolium salts 4a and 4b.
The synthesis of proline-based imidazolium salts 4a and 4b is
shown in Scheme 1. Treatment with benzyl chloride (1.15 equiv)
and KOH (3.0 equiv), commercially available rac-proline (0.15 mol)
was transformed into N-benzyl proline 1 in 85% yield,6 which gave
the corresponding N-benzyl prolinol 2 in 95% yield by reduction
Scheme 2 shows another route for the synthesis of NeTs proline
derived imidazolium salt 8 according to the previous literature.9
Reduction of proline with LiAlH4 gave prolinol 5 in 95% yield.
Treatment of prolinol 5 with excess of toluenesulfonyl chloride
(TsCl) afforded product 6 in 65% yield. The reaction of 6 with imi-
dazolium sodium salt gave imidazolium derivative 7 in 89% yield.
Finally, the desired imidazolium salt 8 was obtained in 92% yield
from the reaction of 7 with methyl iodide (Scheme 2).
* Corresponding author. Tel./fax: þ86 577 8837 3111; e-mail address: Shaolix@
wzu.edu.cn (L.-X. Shao).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.08.021

Y.-Q. Tang et al. / Tetrahedron 66 (2010) 7970e7974
7971
(a)
(b)
OTs
N
CH2OH
COOH
N
H
N
H
Ts
6
5
Me
N
N
(c)
(d)
N
N
N
Ts
N
Ts
I
7
8
Scheme 2. Synthesis of proline-based imidazolium salt 8.
2.2. Synthesis of Pd(II)eNHC Complexes
Initial investigations for the preparation of Pd(II)eNHC com-
plexes involved the reaction of imidazolium salt 4a (1.0 mmol) with
PdCl2 (1.0 equiv) in THF under reflux for 22 h in the presence of
NaBr or LiBr.10 Disappointingly, it was found that Pd(II)eNHC
complex 9a was only obtained in 17e26% yields and a plenty of
palladium black was observed in these cases. In a second round, the
reaction of 4a (1.0 mmol) with Pd(OAc)2 (0.5 equiv) was carried out
at room temperature in THF in the presence of NaOtBu (1.0 equiv),
and it was found that complex 9a can be obtained only in 6% yield.
In a third round, to our pleasure, by treatment of imidazolium salt
4a (1.0 mmol) with PdCl2 (0.5 equiv) in THF (12 mL) at reflux
temperature for 16 h, the corresponding Pd(II)eNHC complex 9a
was obtained in 85% yield. Complexes 9b can also be obtained
through this method in 61% yield (Scheme 3). These complexes are
air and moisture stable in solid state and even in the solution state.
The structures of complexes 9a and 9b were fully determined by X-
ray single crystal diffraction (Figs. 1 and 2) and their CIF data are
presented in the Supplementary data.11,12 The central palladium
Figure 2. ORTEP drawing of complex 9b with thermal ellipsoids at the 30% probability
ꢀ
level. Selected bond distances (A) and angles (deg): PdeC15¼1.961(5), PdeN1¼2.152(4),
PdeBr1¼2.4906(8), PdeBr2¼2.4298(7),
C
15ePdeN1¼89.21(19),
C15ePdeBr2¼88.92
(16), N1ePdeBr1¼93.43(12), Br2ePdeBr1¼89.52(3).
atom in both Pd(II) complexes is C, N-coordinated by one ligand
from the carbene and the pyrrolidine nitrogen atom, which to-
gether with the two bromine atoms gives the square planar co-
ordination (Figs. 1 and 2). Both structures showed that each of the
Pd(II) center is an almost perfect normal square planar coordination
with the angles around 90ꢀ, which suggests that the complexes
only have little rigid geometry. Representative data of bond dis-
tances and angles are also shown in the corresponding Figures.
The synthesis of Pd(II)eNHC complex 10 with chloride ion was
accomplished via the transmetallation route with Ag2O.13 Adding
Ag2O (0.5 equiv) to the solution of imidazolium 4a (1.0 mmol) in
CH2Cl2 (10 mL) under exclusion of light for 11 h, then treatment of
the in situ formed AgeNHC complex with PdCl2(CH3CN)2
(1.0 equiv) for 7 h in CH2Cl2 gave the Pd(II)eNHC complex 10 in 65%
yield (Scheme 4). The structure of complex 10 was also fully de-
termined by X-ray single crystal diffraction (Fig. 3) and its CIF data
are presented in the Supplementary data.14 In this case, similar
coordinative pattern for the palladium center was found and the
central palladium atom is also square planar coordinated with the
angles around 90ꢀ (Fig. 3). Representative data of bond distances
and angles are also shown in Figure 3.
N
R
N
R
PdCl2
THF, reflux, 16 h
N
.
.
N
N
N
Br
Pd
Ph
Ph
4a: R = Me
4b: R = Et
Br
Br
9a: R = Me, 85%
9b: R = Et, 61%
Scheme 3. Synthesis of PdeNHC complexes 9a and 9b.
(1) Ag2O, CH2Cl2,
rt, 11 h
(2) PdCl2(CH3CN)2,
Me
N
Me
N
N
.
.
N
N
N
Br
Pd
CH2Cl2, rt, 7 h
Ph
Ph
Cl
4a
Cl
10, 65%
Scheme 4. Synthesis of PdeNHC complex 10.
Treatment of imidazolium salt 8 with Pd(OAc)2 in the presence
of NaOtBu in THF at room temperature for 16 h, another type of
complex 11, as a mixture of cis- and trans-isomers in the ratio of
about 1:1, was achieved in 47% yield (Scheme 5). The structure
of the cis-complex 11 was also fully determined by X-ray single
crystal diffraction (Fig. 4) and its CIF data are presented in the
Supplementary data.15 A dimeric mono-coordinated NHCePd(II)
complex was obtained in this case and it clearly showed that the
N-atom substituted with Ts group in the pyrrolidine ring do not
coordinate to the palladium center because of its lack of
coordinative electrons. Pd(II) center lies also in a normal square
planar coordination state. Representative data of bond distances
and angles for this complex are also shown in Figure 4.
Figure 1. ORTEP drawing of complex 9a with thermal ellipsoids at the 30% probability
ꢀ
level. Selected bond distances (A) and angles (deg): PdeC15¼1.960(4), PdeN1¼2.154(3),
PdeBr1¼2.5084(6), PdeBr2¼2.4278(6),
C
15ePdeN1¼88.79(13),
C
15ePdeBr2¼89.55
(11), N1ePdeBr1¼92.69(8), Br2ePdeBr1¼89.970(19).

7972
Y.-Q. Tang et al. / Tetrahedron 66 (2010) 7970e7974
3. Conclusion
In conclusion, we present the synthesis and structural charac-
terization of new Pd(II)eNHC complexes derived from proline in
this paper. All the complexes reported have been fully determined
by X-ray single crystal diffraction. It was found that the substituents
on the N-atom of the pyrrolidine skeleton dramatically affect on the
coordination pattern of the palladium center. In a word, when an
electron-rich group as benzyl group was attached on the N-atom,
both of the N-atom and NHC were coordinated to the Pd(II) center;
while when an electron-poor group as Ts group was attached,
a dimeric mono-coordinated NHCePd(II) was obtained exclusively.
4. Experimental section
4.1. General methods
1H and 13C NMR spectra were recorded on a Bruker Avance-
300 MHz or Bruker AV-III 500 MHz spectrometer for solution in
CDCl3 with tetramethylsilane (TMS) as an internal standard or in
DMSO-d6; J-values are in hertz. Mass spectra were recorded with
Figure 3. ORTEP drawing of complex 10 with thermal ellipsoids at the 30% probability
ꢀ
level. Selected bond distances (A) and angles (deg): PdeC15¼1.956(4), PdeN1¼2.124(3),
a HP-5989 instrument. Satisfactory CHN microanalyses were
PdeCl1¼2.3882(13), PdeCl2¼2.3152(11),
C
15ePdeN1¼88.86(14),
C15ePdeCl2¼89.69
obtained via a Carlo-Erba 1106 analyzer. X-ray diffraction analysis
was performed on a Bruker Smart APEX CCD X-ray diffraction
meter. THF was distilled from sodium (Na) under nitrogen (N2)
atmosphere. CH3CN and CH2Cl2 were distilled from CaH2 under
nitrogen (N2) atmosphere. Commercially obtained reagents were
used without further purification. Flash column chromatography
was carried out using Huanghai 300e400 mesh silica gel at in-
creased pressure.
(11), N1ePdeCl1¼91.86(10), Cl2ePdeCl1¼89.98(5).
Me
N
N
I
.
.
I
N
Pd
Me
Pd(OAc)2, NaOBut
N
Me
Ts
.
.
4.2. Experimental procedures
N
N
THF, rt, 16 h
N
Ts
N
I
4.2.1. Synthesis of compound 16. To a dry 250 mL flask,
D, L-proline
N
Ts
(17.3 g, 150 mmol) and potassium hydroxide (25.40 g, 450 mmol)
were dissolved in isopropanol (100 mL) and heated to 40 ꢀC. Benzyl
chloride (20.0 mL, 170 mmol) was added slowly over 3 h via
a dropping funnel. The reaction mixture was stirred overnight at
the same temperature and then was allowed to cool to room
temperature. Concentrated HCl was added to adjust the PH of so-
lution to 4e5. Chloroform (40 mL) was added and the reaction
mixture was allowed to stir at room temperature for 12 h. The re-
action mixture was filtered to remove the white precipitate and the
precipitate was washed with chloroform (3ꢁ20 mL). The organic
layers were combined and concentrated to yield a pale viscous
liquid, which was treated with acetone (100 mL). A large amount of
white solid appeared. The mixture was further cooled to 0 ꢀC, and
then was filtered and the precipitate was washed with cold acetone
(3ꢁ50 mL). The solid was dried under vacuum to yield the benzy-
lated acid 1 (26.21 g, 85%) as a white solid, which was used further
without any purification. 1H NMR (CDCl3, TMS, 300 MHz):
8
11, 47%
Scheme 5. Synthesis of PdeNHC complex 11.
d
1.92e2.09 (m, 2H), 2.23e2.40 (m, 2H), 3.00 (dd, J¼18.9, 9.0 Hz,
1H), 3.67e3.74 (m, 1H), 3.92 (t, J¼7.5 Hz, 1H), 4.33 (d, J¼12.6 Hz,
1H), 4.41 (d, J¼12.6 Hz, 1H), 6.42 (br, 1H), 7.38e7.48 (m, 5H, Ar).
4.2.2. Synthesis of compound 27. Under N2 atmosphere, to a dry
500 mL flask, the benzylated acid 1 (26.2 g, 127.8 mmol) was added
to a suspension of LiAlH4 (7.60 g, 191.5 mmol) in tetrahydrofuran
(240 mL) at 0 ꢀC. The reaction mixture was refluxed for 3 h. After
cooling to room temperature, the excess of LiAlH4 was treated with
20% aq KOH (16 mL). The reaction mixture was filtered and the
residue was refluxed with new tetrahydrofuran (150 mL) for
30 min. the reaction mixture was filtered. The combined tetrahy-
drofuran filtrates were dried over anhydrous Na2SO4 and evapo-
rated to yield product 2 (23.2 g, 96%) as a yellow liquid. 1H NMR
Figure 4. ORTEP drawing of complex 11 with thermal ellipsoids at the 30% probability
ꢀ
level. Selected bond distances (A) and angles (deg): PdeC16¼2.023(11), PdeC17¼2.005
(11), PdeI1¼2.6482(12), PdeI2¼2.6464(12), C17ePdeC16¼93.6(5), C16ePdeI1¼87.2(3),
C
17ePdeI2¼87.0(3), I2ePdeI1¼93.20(4).
(CDCl3, TMS, 300 MHz): d 1.66e1.97 (m, 4H), 2.25e2.34 (m, 1H),

Y.-Q. Tang et al. / Tetrahedron 66 (2010) 7970e7974
7973
2.51 (br, 1H), 2.72e2.76 (m, 1H), 2.95e3.01 (m, 1H), 3.36 (d,
J¼12.9 Hz, 1H), 3.43 (dd, J¼10.5, 2.1 Hz, 1H), 3.66 (dd, J¼10.5, 3.3 Hz,
1H), 3.97 (d, J¼12.9 Hz, 1H), 7.25e7.32 (m, 5H, Ar); 13C NMR (CDCl3,
(d, J¼8.4 Hz, 2H, Ar), 7.82 (d, J¼8.4 Hz, 2H, Ar); 13C NMR (CDCl3,
125 MHz):
d 21.49, 21.63, 23.71, 28.49, 49.30, 57.62, 71.44, 127.52,
127.97, 129.77, 129.94, 132.54, 133.46, 143.84, 145.02.
75 MHz): d 23.3, 27.7, 54.3, 58.4,61.7, 64.1, 126.9, 128.2, 128.6, 139.2.
4.2.8. Synthesis of compound 7. A solution of Imꢂ Naþ (1.23 g,
13.6 mol) and compound 6 (2.05 g, 5.0 mmol) in THF (25 mL) was
refluxed for 24 h. Then the solution was filtered and the filter cake
was washed with THF. The combined filtrate was concentrated in
vacuo and the residue was purified by a flash chromatography on
silica gel (eluent: ethyl acetate) to give compound 7 (1.33 g, 89%) as
a white solid. Mp: 115e116 ꢀC. 1H NMR (CDCl3, TMS, 300 MHz):
4.2.3. Synthesis of compound 3. To a solution of compound 2
(10.0 g, 52.4 mmol) and PPh3 (20.02 g, 76.3 mmol) in anhydrous
THF (150 mL) was added CBr4 (25.00 g, 75.3 mmol) slowly at 0 ꢀC.
The reaction mixture was allowed to warm slowly to room tem-
perature and stirred at that temperature for an additional 2 h. Then
the reaction mixture was poured into saturated aq NaHCO3 to reach
a pH of 7e8, extracted with CH2Cl2, washed with brine, dried over
anhydrous Na2SO4. The solvent was removed under reduced pres-
sure and the residue was purified by a flash chromatography on
silica gel (eluent: petroleum ether/ethyl acetate, 20:1) to give
compound 3 (10.22 g, 76%) as a pale-yellow liquid. 1H NMR (CDCl3,
d
1.22e1.45 (m, 2H), 1.60e1.67 (m, 2H), 2.45 (s, 3H), 30.2e3.10 (m,
1H), 3.28e3.35 (m, 1H), 3.78e3.85 (m, 1H), 4.25 (dd, J¼14.4, 3.0 Hz,
1H), 4.35 (dd, J¼14.4, 5.7 Hz, 1H), 7.11 (s, 2H), 7.36 (d, J¼8.1 Hz, 2H),
7.74 (d, J¼8.1 Hz, 2H), 7.80 (s, 1H); 13C NMR (CDCl3, 125 MHz):
d
21.52, 23.63, 29.09, 49.37, 51.56, 59.59, 120.10, 127.52, 129.45,
TMS, 300 MHz):
d
1.60e1.78 (m, 3H), 2.08e2.38 (m, 3H), 2.73 (d,
129.89, 133.60, 137.73, 144.01. IR (neat) n 3029, 2943, 2797, 2756,
J¼10.8 Hz, 1H), 3.08 (d, J¼10.8 Hz, 1H), 3.51(d, J¼13.8 Hz, 1H), 3.55
1740, 1494, 1453, 1345, 1217, 1181, 1149, 1072, 1028, 982, 873, 794,
738, 712 cmꢂ1. MS (ESI) m/z 306 [Mþ1]þ. HRMS (ESI) calcd for
C15H20N3O2S: requires 306.1271, found: 306.1266.
(d, J¼13.8 Hz, 1H), 4.08e4.17 (m, 1H), 7.22e7.34 (m, 5H, Ar); 13C
NMR (CDCl3, 75 MHz): d 25.8, 35.6, 48.3, 52.7, 61.7, 62.6, 127.1, 128.2,
128.9, 137.7. MS (ESI) m/z 254 [Mþ1]þ. IR (neat)
n 2959, 2874, 1596,
1507, 1447, 1338, 1289, 1233, 1151, 1092, 1039, 990, 818, 745,
711 cmꢂ1. HRMS (ESI) calcd for C12H17BrN: requires 254.0539,
found: 254.0509.
4.2.9. Synthesis of compound 89. To a CH3CN (15 mL) solution
containing compound 7 (1.0234 g, 3.3 mmol) was added MeI
(0.4 mL, 6.4 mmol) at room temperature. The reaction mixture was
stirred under reflux for 20 h. The solution was concentrated in
vacuo and obtained a yellow solid, which was washed with Et2O
(3ꢁ10 mL) to afford compound 8 as a pale-yellow solid (1.3492 g,
4.2.4. Synthesis of compound 4a. A solution of N-methylimidazole
(1.8 mL, 22 mmol) and compound 3 (5.10 g, 20 mmol) in CH3CN
(60 mL) was stirred at 50 ꢀC for 16 h. The solvent was removed
under reduced pressure and the residue was dissolved in water, and
washed with CH2Cl2 (3ꢁ20 mL). Then the aqueous layer was
92%). 1H NMR (CDCl3, TMS, 300 MHz):
d 1.41e1.83 (m, 4H), 2.43 (s,
3H), 3.07e3.16 (m, 1H), 3.49e3.56 (m, 1H), 4.08 (s, 3H), 4.10e4.17
(m, 1H), 4.56 (dd, J¼13.8, 6.6 Hz, 1H), 4.72 (dd, J¼13.8, 9.6 Hz, 1H),
7.36 (d, J¼8.4 Hz, 2H, Ar), 7.53 (dd, J1¼J2¼1.5 Hz, 1H), 7.71 (d,
J¼8.4 Hz, 2H, Ar), 7.84 (dd, J1¼J2¼1.5 Hz, 1H), 9.87 (s, 1H); 13C NMR
evaporated to give 4a as a pale-yellow liquid (6.6 g, 98%). IR (neat)
n
3407, 3142, 3061, 2953, 2811, 1618, 1572, 1495, 1452, 1376, 1168,
1117, 1075, 1027, 825, 733, 705 cmꢂ1; MS (ESI) m/z 257 [MꢂBrþ1]þ.
(CDCl3, 125 MHz): d 21.40, 23.79, 28.77, 36.83, 49.37, 52.79, 59.63,
122.85, 123.77, 127.53, 129.97, 132.70, 137.00, 144.21.
4.2.5. Synthesis of compound 4b. The same procedure for the syn-
thesis of compound 4a was used and 4b was obtained as a pale-
4.2.10. Synthesis of compound 9a. Under N2 atmosphere, a mixture
of compound 4a (336.2 mg, 1.0 mmol) and PdCl2 (89.1 mg,
0.5 mmol) was stirred in anhydrous THF (12 mL) under reflux for
20 h. The solvent was removed under reduced pressure, and the
residue was purified by a flash chromatography on silica gel
(CH2Cl2/EtOH, 100:1) to give NHCePd(II) complex 9a (225.2 mg,
85%) as a yellow solid. The single crystal for X-ray diffraction was
obtained by recrystallization from CH2Cl2 and ethyl acetate. Be-
cause of its poor solubility in routine solvents as CDCl3, DMSO-d6,
CD3CN, D2O, acetone-d6, so there is no good 1H NMR and 13C NMR
spectroscopy data for this compound. Mp: 172.2 ꢀC (decomposed).
yellow liquid (7.2 g, 96%). IR (neat)
n 3419, 3061, 2971, 2806, 1634,
1562, 1495, 1452, 1355, 1164, 1120, 1075, 1027, 872, 740, 720 cmꢂ1
;
MS (ESI) m/z 270 [MꢂBr]þ.
4.2.6. Synthesis of compound 5. Under N2 atmosphere D, L-proline
(17.30 g, 150 mmol) was added to a suspension of LiAlH4 (8.53 g,
225 mmol) in anhydrous tetrahydrofuran (250 mL) at 0 ꢀC. The
reaction mixture was refluxed for 2 h. After cooling to room tem-
perature, the excess of LiAlH4 was treated with 20% aq KOH (18 mL).
The reaction mixture was filtered and the residue was refluxed with
new tetrahydrofuran (150 mL) for 30 min. The reaction mixture was
filtered. The combined tetrahydrofuran filtrates were dried over
anhydrous Na2SO4 and evaporated to yield compound 5 (14.63 g,
IR (neat)
n 3569, 3486, 3162, 3121, 3096, 2951, 1603, 1473, 1454,
1407, 1227,1190,1088, 951, 917, 740, 705 cmꢂ1. MS (ESI) m/z 440 [M-
Br]þ. Anal. Calcd for C16H21Br2N3Pd requires: C, 36.84%; H, 4.06%; N,
8.06%; found: C, 37.39%; H, 4.30%, N, 8.20%. HRMS (MALDI) calcd for
C16H21BrN3102Pdþ: requires 435.9969, found: 435.9955.
96%) as a yellow liquid. 1H NMR (CDCl3, 300 MHz, TMS):
d 1.35e1.46
(m, 1H),1.65e1.87 (m, 3H), 2.90 (t, J¼6.9 Hz, 2H), 3.20e3.28 (m, 1H),
3.36 (dd, J¼10.8, 7.8 Hz, 1H), 3.55 (dd, J¼10.8, 6.9 Hz, 1H), 3.74
(br, 1H).
4.2.11. Synthesis of compound 9b. The same procedure for the
synthesis of compound 9a was used and 9b was obtained as a yel-
low solid (163.1 mg, 61%). The single crystal for X-ray diffraction
was obtained by recrystallization from CH2Cl2 and ethyl acetate.
4.2.7. Synthesis of compound 69. To a stirred solution of 5 (4.30 g,
42.6 mmol) and Et3N (24 mL, 173 mmol) in anhydrous CH2Cl2
(20 mL) at 0 ꢀC was added p-toluenesulfony1 chloride (24.40 g,
127.8 mmol). The mixture was stirred at room temperature for 4 h
and extracted with EtOAc. The extract was washed with water and
brine, dried over anhydrous Na2SO4, and evaporated. Then the
residue was purified by a flash chromatography on silica gel (pe-
troleum ether/ethyl acetate, 2:1) to give compound 6 (11.25 g, 65%)
Mp: 171.2 ꢀC (decomposed). IR (neat)
n 3141, 3104, 3083, 2967,
2930, 2868, 1470, 1452, 1428, 1265, 1218, 1183, 948, 913, 780, 744,
703 cmꢂ1. MS (ESI) m/z 456 [MꢂBr]þ. Anal. Calcd for C17H23Br2N3Pd
requires: C, 38.12%; H, 4.33%; N, 7.85%; found: C, 38.72%; H, 4.68%, N,
7.96%. HRMS (MALDI) calcd for C17H23BrN3102Pdþ: requires
450.0126, found: 450.0130.
as a white solid. 1H NMR (CDCl3, TMS, 300 MHz):
d 1.51e1.92 (m,
4H), 2.43 (s, 3H), 2.47 (s, 3H), 2.99e3.69 (m, 1H), 3.36e3.43 (m, 1H),
3.71e3.76 (m, 1H), 3.96 (dd, J1¼J2¼9.9 Hz, 1H), 4.25 (dd, J¼9.9,
3.6 Hz, 1H), 7.31 (d, J¼8.1 Hz, 2H, Ar), 7.38 (d, J¼8.1 Hz, 2H, Ar), 7.66
4.2.12. Synthesis of compound 10. Under N2 atmosphere, to a solu-
tion of compound 4a (336.6 mg, 1.0 mmol) in CH2Cl2 (10 mL) was
added Ag2O (116.0 mg, 0.5 mmol), and the mixture was stirred at

7974
Y.-Q. Tang et al. / Tetrahedron 66 (2010) 7970e7974
room temperature under exclusion of light for 11 h. Then the re-
action mixture was filtered and to the filtrate was added Pd
(CH3CN)2Cl2 (259.3 mg, 1.0 mmol). After stirring at room temper-
ature for 7 h, the mixture was filtered through Celite. The solvent
was removed under reduced pressure and the residue was purified
by a flash chromatography on silica gel (CH2Cl2/EtOH¼100:1) to
give NHCePd(II) complex 10 (290.5 mg, 65%) as a yellow solid. Mp:
184.5 ꢀC (decomposed). 1H NMR (CDCl3, TMS, 300 MHz):
References and notes
1. Arduengo, A. J., III; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991, 113, 361e363.
2. For recent selected reviews on NHCs, please see: (a) Glorius, F. N-Heterocyclic
Carbenes in Transition Metal Catalysis; Springer: Berlin, 2007; (b) N-Heterocyclic
Carbenes in Synthesis; Nolan, S. P., Ed.; Wiley-VCH: Weinheim, Germany, 2006;
(c) Díez-González, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612e3676;
(d) Marion, N.; Nolan, S. P. Acc. Chem. Res. 2008, 41, 1440e1449; (e) Hahn, F. E.;
Jahnke, M. C. Angew. Chem., Int. Ed. 2008, 47, 3122e3172; (f) Pugh, D.; Dano-
poulos, A. A. Coord. Chem. Rev. 2007, 251, 610e641; (g) Kantchev, E. A. B.;
O’Brien, C. J.; Organ, M. G. Angew. Chem., Int. Ed. 2007, 46, 2768e2813; (h) Peris,
E.; Crabtree, R. H. Coor. Chem. Rev. 2004, 248, 2239e2246; (i) César, V.; Belle-
min-Laponnaz, S.; Gade, L. H. Chem. Soc. Rev. 2004, 33, 619e636.
3. (a) Liddle, S. T.; Edworthy, I. S.; Arnold, P. L. Chem. Soc. Rev. 2007, 36, 1732e1744;
(b) Normand, A. T.; Cavell, K. J. Eur. J. Inorg. Chem. 2008, 2781e2800; (c) Cor-
beran, R.; Mas-Marza, E.; Peris, E. Eur. J. Inorg. Chem. 2009, 1700e1716.
4. (a) Bonnet, L. G.; Douthwaite, R. E.; Hodgson, R.; Houghton, J.; Kariuki, B. M.;
Simonovic, S. Dalton Trans. 2004, 3528e3535; (b) Douthwaite, R. E.; Houghton,
J.; Kariuki, B. M. Chem. Commun. 2004, 698e699; (c) Houghton, J.; Dyson, G.;
Douthwaite, R. E.; Whitwood, A. C.; Kariuki, B. M. Dalton Trans. 2007,
3065e3073; (d) Wylie, W. N. O.; Lough, A. J.; Morris, R. H. Organometallics 2009,
28, 6755e6761; (e) Jimenez, M. V.; Perez-Torrente, J. J.; Bartolome, M. I.; Gierz,
V.; Lajoz, F. J.; Oro, L. A. Organometallics 2008, 27, 224e234; (f) Jong, H.; Patrick,
B. O.; Fryzuk, M. D. Can. J. Chem. 2008, 86, 803e810.
d
1.70e1.81 (m, 1H), 1.99e2.13 (m, 2H), 2.29e2.39 (m, 1H), 3.02 (t,
J¼9.3 Hz,1H), 3.37 (d, J¼12.0 Hz,1H), 3.67 (s, 3H), 3.90 (d, J¼13.8 Hz,
1H), 3.97e4.08 (m, 1H), 4.24 (d, J¼10.8 Hz, 1H), 4.29 (d, J¼10.8 Hz,
1H), 4.70 (d, J¼12.0 Hz, 1H), 6.58 (d, J¼1.5 Hz, 1H), 6.96 (d, J¼1.5 Hz,
1H), 7.30e7.37 (m, 3H, Ar), 8.06 (d, J¼6.9 Hz, 2H, Ar); 13C NMR
(CDCl3, 125 MHz):
d 25.18, 38.62, 53.40, 54.26, 61.54, 62.34, 63.79,
120.10, 122.88, 128.45, 128.81, 131.93, 135.01, 150.38. MS (ESI) m/z
396 [MꢂCl]þ. IR (neat)
n 3573, 3477, 3162, 3125, 3096, 2955, 2868,
1603, 1475, 1454, 1408, 1228, 1192, 949, 918, 807, 746, 706 cmꢂ1
.
Anal. Calcd for C16H23Cl2N3OPd requires: C, 42.64%; H, 5.14%, N,
9.32%; found: C, 42.83%; H, 5.33%, N, 9.43%. HRMS (MALDI) calcd for
C16H21N3Br102Pdþ: requires 392.0475, found: 392.0461.
5. Boronat, M.; Corma, A.; González-Arellano, C.; Iglesias, M.; Sánchez, F. Organ-
ometallics 2010, 29, 134e141.
6. (a) Belokon, Y. N.; Tararov, V. I.; Maleev, V. I.; Savel’eva, T. F.; Ryzhov, M. G.
Tetrahedron: Asymmetry 1998, 9, 4249e4252; (b) Traverse, J. F.; Zhao, Y.;
Hoveyda, A. H.; Snapper, M. L. Org. Lett. 2005, 7, 3151e3154.
7. Wallen, E. A. A.; Christiaans, J. A. M.; Forsberg, M. M.; Venalainen, J. I.; Mannisto,
P. T.; Gynther, J. J. Med. Chem. 2002, 45, 4581e4584.
8. Kawabata, T.; Moriyama, K.; Kawakami, S.; Tsubaki, K. J. Am. Chem. Soc. 2008,
130, 4153e4157.
9. Zhang, W.-F.; Qin, Y.-C.; Zhang, S.-J.; Luo, M.-M. ARKIVOC 2005, xiv, 39e48.
10. Huynh, H. V.; Han, Y.; Ho, J. H. H.; Tan, G. K. Organometallics 2006, 25,
3267e3274.
4.2.13. Synthesis of compound 11. Under N2 atmosphere, a mixture
of compound 10 (223.2 mg, 0.50 mmol), Pd(OAc)2 (56 mg,
0.25 mmol), and NaOtBu (48.1 mg, 0.5 mmol) was stirred in anhy-
drous THF (12 mL) at room temperature for 16 h. The solvent was
removed under reduced pressure, and the residue was purified by
a flash chromatography on silica gel (CH2Cl2/ethyl acetate, 20:1) to
give Pd(II)eNHC complex 11 as a yellow solid (117 mg, 47%). The
single crystal for X-ray diffraction was obtained by recrystallization
11. The crystal data of complex 9a has been deposited in CCDC with number
761757. Empirical Formula: C16H21Br2N3Pd; Formula Weight: 521.58; Crystal
Color, Habit: colorless, prismatic; Crystal System: Monoclinic Lattice Type:
from CH2Cl2, ethanol, and ethyl acetate. IR (neat) n 2947, 2922,1589,
1465, 1404, 1344, 1239, 1194, 1161, 1093, 1042, 987, 820, 730 cmꢂ1
.
ꢀ
ꢀ
Primitive; Lattice Parameters: a¼9.2705(13) A, b¼14.1816(19) A, c¼13.7065
3
ꢀ
¼90ꢀ,
b
¼102.129(2)ꢀ,
¼90 , V¼1761.8(4) A ; Space group: P21/c; Z¼4;
g
ꢀ
ꢀ
Mp: 299.3 ꢀC (decomposed). MS (ESI) m/z 871 [MꢂI]þ. Anal. Calcd
for C32H42N6O4S2I2Pd$1/3CH2Cl2: requires C, 37.80%; H, 4.19%, N,
8.18%; found: C, 37.80%; H, 4.07%, N, 8.00%. HRMS (MALDI) calcd for
C32H42N6O4S2I102Pdþ: requires 867.0824, found: 867.0804.
(18) A,
a
Dcalcd¼1.966 g/cm3; F000¼1016; Diffractometer: Bruker Smart APEX CCD; Re-
siduals: R; Rw: 0.0288, 0.0768.
12. The crystal data of complex 9b has been deposited in CCDC with number
761,753. Empirical Formula: C17H23Br2N3Pd; Formula Weight: 535.60; Crystal
Color, Habit: colorless, prismatic; Crystal System: Monoclinic; Lattice Type:
ꢀ
ꢀ
Primitive; Lattice Parameters: a¼9.6028(9) A, b¼14.5618(13) A, c¼13.8519
3
ꢀ
ꢀ
¼90ꢀ,
b
¼102.888(2)ꢀ,
g
¼90 , V¼1888.2(3) A ; Space group: P2(1)/c;
ꢀ
Acknowledgements
(13) A,
a
Z¼4; Dcalcd¼1.884 g/cm3; F000¼1048; Diffractometer: Bruker Smart APEX CCD;
Residuals: R; Rw: 0.0464, 0.1122.
Financial support from the National Natural Science Foundation
of China (No. 20702013) and the start-up fund of Wenzhou Uni-
versity is greatly acknowledged. J.-M.L. thanks the Department of
Education of Zhejiang Province for financial support (No.
Y200907072).
13. Wang, H. M. I.; Lin, I. J. B. Organometallics 1998, 17, 972e975.
14. The crystal data of 10 has been deposited in CCDC with number 761755. Em-
pirical Formula: C16H23Cl2N3OPd; Formula Weight: 450.67; Crystal Color, Habit:
colorless, prismatic; Crystal System: Orthorhombic; Lattice Type: Primitive;
ꢀ
ꢀ
ꢀ
a
Lattice Parameters: a¼8.5445(6) A, b¼13.6489(9) A, c¼15.6269(10) A,
¼90ꢀ,
3
ꢀ
b
¼90ꢀ,
g
¼90ꢀ, V¼1822.5(2) A ; Space group: P212121; Z¼4; Dcalcd¼1.643
g/cm3; F000¼912; Diffractometer: Bruker Smart APEX CCD; Residuals: R; Rw: 0.
0326, 0.0746.
Supplementary data
15. The crystal data of 11 has been deposited in CCDC with number 761758. Em-
pirical Formula: C32H41I2N6O4PdS2; Formula Weight: 998.03; Crystal Color,
Habit: colorless, prismatic; Crystal System: Monoclinic; Lattice Type: Primitive;
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2010.08.021. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
ꢀ
ꢀ
ꢀ
a
Lattice Parameters: a¼10.3040(8) A, b¼24.1974(19) A, c¼18.9602(15) A,
¼90ꢀ,
3
ꢀ
ꢀ
b
¼102.979(2)ꢀ,
g
¼90 , V¼4606.6(6) A ; Space group: P21/n; Z¼4; Dcalcd¼1.
439 g/cm3; F000¼1964; Diffractometer: Bruker Smart APEX CCD; Residuals: R;
Rw: 0.0913, 0.2376