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2.4. Catalytic carbonylations of alkynes using ligand L3 or complex Pd
(L3)Cl2
2. Experimental
2.1. Materials and methods
In the glove box, a 4 mL screw-cap vial was charged with Pd-
catalyst (1.0 mol%), ligand L3 (4.0 mol%), methanesulfonic acid
(MSA) (6.0 mol%), solvent (1 mL), and an oven-dried stirring bar.
After stirring for 15 min, alkyne (0.5 mmol) and alcohols (1.0
mmol) were injected into the vial. The vial was closed by PTFE/
white rubber septum (Wheaton 13 mm Septa) and phenolic cap,
and connected with atmosphere with a needle, and fixed in an
alloy plate, and put into the autoclave (250 mL) under argon atmo-
sphere. At room temperature, the autoclave was flushed with CO
gas five times and pressurized with CO gas to 30 bar. The reaction
was performed at 80 °C for 12 h. After that, the autoclave was
cooled to room temperature and the pressure was carefully
released. Hexadecane was added as an internal standard. A sample
of the mixture was taken and analyzed by GC-FID (Shimadzu GC-
2010) and GC–MS (Agilent GC–MS 7890A-5975C). Pure product
could be obtained by column chromatography on silica gel using
petroleum ether/ethyl acetate as eluents with a gradient ratio of
100:1–50:1.
All materials were purchased from commercial sources and
used without further purification. Solvents were dried by solvent
purification system from LC Technology Solution Inc. CO (99.95%)
was purchased from Messer (Wujiang, China). GC data obtained
through Shimadzu GC-2010 Plus. All 1H and 13C NMR spectra were
recorded on Bruker 400 MHz spectrometer. HRMS data were
obtained on Agilent 6530 spectrometer. X-ray data collection from
Bruker SMART APEX diffractometer.
Diffraction intensity for complex Pd(L3)Cl2 is collected on a Bru-
ker SMART APEX diffractometer system equipped with graphite
monochromatic Mo Ka radiation (k = 0.71073 Å) at 296 K. An
empirical absorption correction using SADABS [11] was applied
for all data. The structure was solved by direct methods using
the SHELXS program. All non-hydrogen atoms were refined
anisotropically by full-matrix least-squares on F2 by the use of
the program SHELXL [12]. Crystallographic data are given in
Table S1 (see the Supplementary Data). Selected bond distances
and angles are given in Table S2. CCDC1821020 contains the sup-
plementary crystallographic data.
3. Results and discussion
2.2. Preparation of ligands (L1-L5)
3.1. Conditions optimization
Ligands L1-L5 were synthesized by coupling dicyclohexylphos-
phine or diphenylphosphine with the corresponding carbazole aryl
halide. Unless otherwise stated, the synthetic method is similar to
the preparation of L3 shown below in two steps.
Step 1: In 150 mL sealed tube, a stirred mixture of CuI (38.1 mg,
0.2 mmol), 1-methylimidazole (41.7 lL, 0.4 mmol), t-BuOLi (2.401
g, 30 mmol), 1-bromo-9H-carbazole (4.922 g, 20 mmol) and 2-
bromopyridine (2.1 mL, 22 mmol) in toluene (70 mL) was heated
to 130 °C. After 12 h, the reaction mixture was allowed to cool to
room temperature, and upon evaporation of solvent a brownish
yellow solid was obtained (1-bromo-9-(pyridin-2-yl)-9H-
carbazole, 95% yield).
We originally investigated methoxycarbonylation of 1-octyne
using different metal precursors and ligands with reactions carried
out under various conditions. Firstly, using PdCl2 as the metal pre-
cursor, the five carbazole-derived ligands were screened. The
results showed that only L3 and L4 having P atom substitution
on 1-position of the carbazole moiety led to good reactivity (83%
yield; Table 1, entries 3–4). By contrast, for the other three ligands
(L1, L2 and L5) having either P atom substitution on 2- and 3-
position on the carbazole or the absence of N-pyridyl group substi-
tution, inferior reactivity was observed under the same reaction
conditions (8–40% yields; Table 1, entries 1, 2 and 5). This result
clearly supports our design strategy and shows the importance of
having Py group at close proximity in space to P atom in both reac-
tivity and selectivity in alkyne alkoxycarbonylations.
In addition, different palladium precursors were screened using
L3 as the ligand showing that both Pd(0) or Pd(II) salts give reason-
able reactivity with similar branched regioselectivity (Table 1,
entries 6–9). The reaction medium was also investigated showing
that two polar solvents were suitable with MeCN as medium giving
better regioselectivity (98.0%; Table 1, entry 11). Hence, MeCN was
chosen as the best reaction medium for these alkyne alkoxycar-
bonylations. Further investigation of acid co-catalysts, reaction
temperature and time, yielded the optimized conditions; 60 °C
with 60 bar of CO for 16 h giving the desired branched product in
89% yield and 99.2% selectivity (Table 1, entry 18). Due to the high
yield obtained, the in-situ formation the catalyst based on ligand L3
and PdCl2 was chosen for subsequent substrate scope study.
Step 2: Pd(OAc)2 (44.9 mg, 0.2 mmol), 1,10-bis(di-i-
propylphosphino)ferrocene (100.4 mg, 0.24 mmol), Cs2CO3 (3.909
g, 12.0 mmol) and 1-bromo-9-(pyridin-2-yl)-9H-carbazole (4.406
g, 10.0 mmol) were added to an oven dried 75 mL sealed tube con-
taining 20 mL toluene in the glove box. After stirring for 1 h at
room temperature, a reddish-brown solution was obtained. Then
dicyclohexylphosphine (12 mmol) were added under a nitrogen
atmosphere, and the mixture was heated to 130 °C, and stirred
for 20 h. After cooling, dichloromethane (30 mL) and water (30
mL) were added and the layers were separated. The aqueous layer
was extracted three times with dichloromethane, the combined
organic extracts were washed with water (three times) and brine.
Then the organic phase was dried with MgSO4 and the solvent was
concentrated to afford a yellow solid. The crude product was puri-
fied by flash column chromatography on silica gel to afford the
desired L3 as a pale yellow solid (89% yield).
3.2. Crystal structure of complex Pd(L3)Cl2
2.3. Preparation of crystals of complex (Pd(L3)Cl2)
In order to understand the coordination behavior of L3 with Pd
center in the catalytic cycle, a good quality single crystal of Pd(L3)
Cl2 has been prepared and its single-crystal structure has been
investigated by the single-crystal X-ray diffraction method. On
crystals bulk analysis, the XRD data from simulation result of the
single-crystal structure and the experimental data of the crystal-
lized powder were in total agreement. Analysis of the single-
crystal X-ray diffraction reveals that Pd(L3)Cl2 crystallizes in mon-
oclinic space group. The asymmetrical unit of Pd(L3)Cl2 consists of
In an oven dried one necked 100 mL round bottom flask, Pd
(PhCN)2Cl2 (44 mg, 0.11 mmol), L3 (52 mg, 0.12 mmol) and
toluene were added under N2. After stirring for 3 h at room tem-
perature, a light yellow solution was obtained. Then, the solvent
is evaporated under reduced pressure and resulted in a pale yellow
solid (yield 85%). The crystals of this complex were obtained by
slow evaporation from a 2:1 DCM/MeCN solvent mixture at room
temperature.