Synthesis and Characterization of N,N-Dimethylformamide-Protected Palladium Nanoparticles and Their Use in the Suzuki-Miyaura Cross-Coupling Reaction.

Herein, the synthesis of new N,N-dimethylformamide (DMF)-protected palladium nanoparticles (Pd NPs-OAc) employing Pd (OAc)2 (= Pd(OCOCH3)2) as the NP precursor is reported. Pd NPs-OAc were comprehensively characterized by transmission electron microscopy, FT-IR, NMR, and X-ray photoelectron spectroscopy to determine the Pd NP size distribution and the coordination state of DMF. Pd NPs-OAc were compared with Pd NPs-Cl, using PdCl2 as the NP precursor. The Suzuki-Miyaura cross-coupling reaction proceeded efficiently in the presence of Pd NPs-OAc and a high catalytic activity was observed with a turnover number of up to 1.5 × 105. Furthermore, the Pd NP-OAc catalysts could be recycled at least five times.

Introduction

As nanoparticles (NPs) become smaller in size, new properties arise that differ from the corresponding properties of the bulk metals,[1] and hence, a wealth of interdependent research has been focused on the fundamentals of NPs and their diverse use across multiple applications. NPs are employed across a diverse range of applications, from the chemical industry to biological fields and as material components in sensors and electronics.[2−5]

Transition metal NPs exhibit high catalytic activity because of their high surface/volume ratio when compared with bulk metals.[6] NPs can be prepared by various synthetic strategies. The final properties of the NPs (e.g., size and stability) are significantly influenced by the choice of the capping agent, reductant, and metal precursor, especially when adopting liquid-phase reduction methods.[6−8] Previously, the synthesis of NPs by employing N,N-dimethylformamide (DMF) as the reductant, capping agent, and solvent has been reported.[9] The DMF-protected method can carried out in the absence of external additives such as additional capping agents (e.g., ionic solvents, functionalized polymers, surfactants, and dendrimers) and reductants (e.g., H2, NaBH4, and LiAlH4). Furthermore, the synthesis of DMF-protected transition metal NPs (e.g., Pd, Ir, Cu, and Fe) has been previously detailed.[10,11] For instance, DMF-protected palladium NPs (Pd NPs-Cl) have been synthesized by employing the DMF-protected method using PdCl2 as the precursor.[11] The catalytic activity of Pd NPs-Cl was investigated in the Suzuki–Miyaura and Mizoroki–Heck cross-coupling reactions and achieved turnover numbers (TONs) of up to 4.5 × 105 and 6.0 × 108, respectively, using iodobenzene as the substrate. Pd NPs-Cl were successfully recycled at least five times in the Suzuki–Miyaura cross-coupling reaction.[11a]

Pd(OAc)2 is more readily reduced than PdCl2.[12] The metal nucleation rate can control the starting precursor. The LaMer diagram model is widely used to explain the formation of metal NPs. The nucleation rate affects the particle size and shape.[12] Herein, the synthesis and characterization of Pd NPs-OAc, derived from Pd(OAc)2, together with the corresponding catalytic activity in the Suzuki–Miyaura cross-coupling reaction is reported and compared with the catalytic activity of Pd NPs derived from PdCl2.

Results and Discussion

Both Pd NPs-OAc and Pd NPs-Cl were prepared via the DMF-based reduction method. Annular dark-field scanning transmission electron microscopy (ADF-STEM) was employed to determine the particle size distribution of Pd NPs-OAc and Pd NPs-Cl (Figure ). A particle size distribution of 3–5 nm was observed for Pd NPs-OAc (Figure a,b), while for Pd NPs-Cl, the particle size distribution ranged from 1 to 2 nm (Figure c,d). The dynamic light scattering (DLS) chart of the Pd NPs-OAc is shown in Figure S6. The difference in particle sizes between Pd NPs-OAc and Pd NPs-Cl is ascribable to the nucleation rate of these precursors.

Figure 1

(a) Annular dark-field scanning transmission electron microscopy (ADF-STEM) image of N,N-dimethylformamide (DMF)-protected palladium nanoparticles (Pd NPs-OAc) (scale bar = 5 nm); (b) particle size distribution of Pd NPs-OAc; (c) ADF-STEM of Pd NPs-Cl (scale bar = 5 nm); and (d) particle size distribution of Pd NPs-Cl.

Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy were employed to determine the coordination state of the DMF layer surrounding the Pd NPs. The FT-IR spectra at 1800–600 cm–1 of the DMF-protected Pd NPs (Figure ) show the interaction of the DMF amide group (e.g., C=O and C–N vibration modes) with the Pd NPs. The DMF C=O and C–N vibration modes in the DMF-protected Pd NPs are observed to shift away from the corresponding peaks associated with the DMF-free solvent. The similarities of the three FT-IR spectra confirm that DMF is present in both Pd NPs-OAc and Pd NPs-Cl. All the peaks that correspond to the DMF-protected Pd NPs are broader than those of the DMF-free solvent, which may result due to an influence of the interaction between the Pd NPs and the DMF molecules. A strong absorption peak is observed at ∼1670 cm–1, which corresponds to the DMF ν(C=O) vibration. The band shifts to lower wavenumbers (from 1674 cm–1 (Figure i) to 1670 cm–1 for Pd NPs-OAc and to 1672 cm–1 for Pd NPs-Cl) and broadens for both the DMF-protected Pd NPs (−OAc and −Cl), suggesting an interaction between the C=O group in DMF and the Pd NPs. The band located at 1386 cm–1 for the DMF-free solvent (Figure ii) shifts to 1400 cm–1 in the DMF-protected Pd NPs-OAc, while a slightly smaller shift is observed for the DMF-protected Pd NPs-Cl to 1388 cm–1. The two absorption bands at 1093 and 1064 cm–1 in the DMF-free solvent are assigned to methyl rocking vibrations (Figure iii).[13] The methyl rocking vibration bands shift to 1049 and 1014 cm–1 in the DMF-protected Pd NPs-OAc. However, for the DMF-protected Pd NPs-Cl, these bands shift to 1045 cm–1. The O–C–N band shifts from 657 to 704 cm–1 in the DMF-protected Pd NPs-OAc, while a greater shift to 704 or 758 cm–1 is observed in the DMF-protected Pd NPs-Cl (Figure iv). The shifts in the C=O and O–C–N vibrations suggest an interaction between the DMF amide groups and the Pd NPs, regardless of the capping agent used.

Figure 2

FT-IR spectra of: (a) Pd NPs-OAc (red), (b) Pd NPs-Cl (blue), and (c) DMF (black).

Furthermore, the NMR spectra of the DMF-protected Pd NPs and DMF-free Pd NPs (Figure S1–S5) show the electronic state of the protons associated with DMF (e.g., formyl and methyl groups). The peaks associated with the protons of the formyl and methyl groups in the DMF-protected Pd NPs were observed to shift away from the corresponding peaks of the DMF-free solvent. Additionally, because the magnitude of the shift varied, the strength of the interaction between DMF and the Pd NPs also differed depending on the precursor used.

The oxidation state of palladium in Pd NPs-Cl and Pd NPs-OAc was examined by X-ray photoelectron spectroscopy (XPS). Two main peaks, Pd 3d5/2 and Pd 3d3/2, are shown in Figure . Peak full widths at half maxima are listed in Table S1. The peaks associated with Pd NPs are higher than that of the Pd metal standard (Pd 3d5/2 335.8 and Pd 3d3/2 340.3 eV).[14] Similar peaks were observed for Pd NPs-Cl and Pd NPs-OAc. There is no substantial difference in the electronic states of Pd NPs-Cl and Pd NPs-OAc. The Pd 3d5/2 spectrum can be deconvoluted into two symmetric peaks for Pd NPs. Two components are assigned to the Pd core and the Pd surface in order of increasing binding energy.[15] Compared with Pd NPs-Cl, the Pd NPs-OAc core component ratio was increased. The broad spectra are related to the particle size.[16]

Figure 3

X-ray photoelectron spectroscopy core level spectra of Pd 3d areas of: (a)Pd NPs-Cl and (b)Pd NPs-OAc.

The catalytic activity of the DMF-protected Pd NPs (−OAc and −Cl) by the Suzuki–Miyaura cross-coupling of bromobenzene (1a) with 4-methylphenylboronic acid (2a) was evaluated. The catalytic conditions and results are expressed in Table . The reaction of 1a (0.5 mmol) with 2a (0.75 mmol), conducted in the presence of Pd NPs-OAc (0.04 mol % based on 1a) and K2CO3 (0.75 mmol) as a base in DMF (2 mL) at 100 °C for 16 h, yielded the desired product 3a in 10% yield (entry 1, Table ).

Table 1

Palladium Nanoparticle (Pd NP)-Catalyzed Suzuki–Miyaura Cross-Coupling Reaction of Bromobenzene (1a) with 4-Methylphenylboronic Acid (2a)a

entry	Pd NPs	solvent	yield (%)b	TONc
1	–OAc	DMF	10	2.5 × 102
2	–OAc	MeOH	9	2.2 × 102
3	–OAc	NMP	25	6.2 × 102
4	–OAc	H2O	45	1.1 × 102
5d	–OAc	DMF/H2O	trace	<2.5 × 101
6d	–OAc	MeOH/H2O	>99 (97)	>2.5 × 102
7d,e	–OAc	MeOH/H2O	87	2.1 × 104
8d,f	–OAc	MeOH/H2O	94	1.1 × 105
9d,g	–OAc	MeOH/H2O	62	1.5 × 105
10d	–OAc	NMP/H2O	83	2.0 × 103
11	–Cl	DMF	30	7.5 × 102
12	–Cl	MeOH	>99	>2.5 × 102
13	–Cl	NMP	22	5.5 × 102
14	–Cl	H2O	61	1.5 × 103
15d	–Cl	DMF/H2O	84	2.1 × 103
16d	–Cl	MeOH/H2O	>99	>2.5 × 103
17d,e	–Cl	MeOH/H2O	93	2.3 × 102
18d,f	–Cl	MeOH/H2O	10	1.2 × 104
19d,g	–Cl	MeOH/H2O	trace	4.4 × 103
20d	–Cl	NMP/H2O	83	2.0 × 103

Conditions: 1a (0.5 mmol), 2a (0.75 mmol), Pd NPs (0.04 mol %), K2CO3 (0.75 mmol), solvent (2 mL), 100 °C, 16 h, under Ar.

Gas chromatography (GC) yield. The number in parentheses shows the isolated yield.

Turnover number = 3a (mol)/Pd NPs (mol).

Solvent ratio = 1:1.

Pd NPs (4 × 10–3 mol %).

Pd NPs (8 × 10–4 mol %).

Pd NPs (4 × 10–4 mol %).

The influence of the solvent was studied by substituting DMF for MeOH (entry 2, Table ), N-methylpyrroridone (NMP) (entry 3, Table ), or H2O (entry 4, Table ), giving 3a in 9, 25, or 45% yield, respectively. Furthermore, the solvents (DMF, MeOH, or NMP) were mixed with H2O at a ratio of 1:1. However, the reaction was limited in DMF/H2O (entry 5, Table ). Conversely, the reaction was enhanced in the presence of MeOH/H2O to quantitatively yield 3a at 97% (entry 6, Table ). In the case of NMP/H2O, the reaction yielded 3a at 83% (entry 10, Table ). On further decreasing the catalyst loading to 0.004, 0.0008, and 0.0004 mol %, the reaction yielded 3a at 87, 94, and 62%, respectively (entries 7–9, Table ). On changing the catalyst to Pd NPs-Cl, the reaction proceeded in a good yield (entries 11–20, Table ). The catalytic activity of Pd NPs-OAc and Pd NPs-Cl was compared, and the highest TON of 1.5 × 105 was achieved in the presence of 4 × 10–4 mol % Pd NPs-OAc (entry 9, Table ).

The Pd NP materials were further screened by the Suzuki–Miyaura cross-coupling reaction of various aryl bromides (1) and arylboronic acids (2) under the same conditions as for entry 6 in Table (Table ). The reaction using electron-donating and electron-withdrawing aryl bromides, such as −OCH3 (1b), −CHO (1c), and −CF3 (1d), with 4-methylphenylboronic acid (2a) gave the corresponding biphenyl derivatives (3b–3d) in good yields (entries 1–3, Table ). 2-Bromopyrridine (1e), 3-bromopyrridine (1f), 2-bromothiophene (1 g), 1-bromonaphthalene (1 h), and 2-bromonaphthalene (1i) reacted with 2a to give the aryl derivatives 3e and 3 g in 36 and 10% yields (entries 4 and 6, Table , respectively) and 3f, 3 h, and 3i in excellent yields (entries 5, 7, and 8, Table ). Additionally, various arylboronic acids reacted with 1a in good yields (entries 9–13, Table ), whereas the reaction between 3-pyridylboronic acid (2 g) and 1a did not yield the aryl derivative 3o.

Table 2

Pd NP-Catalyzed Suzuki–Miyaura Cross-Coupling Reaction of Bromoaryl (1) with Arylboronic Acid (2)a

Conditions: same as entry 6, Table . Yield of the isolated product after purification.

At 24 h.

At 48 h.

Not detected by GC.

The recycling ability of the DMF-protected Pd NPs in the Suzuki–Miyaura cross-coupling reaction was evaluated. Under reduced catalyst loadings (0.0004 mol %) and base-free conditions (entries 7 and 17, Table ), the (4-methylphenyl)cyclic-triolborate potassium salt (2 h) replaced 4-methylphenylboronic acid (2a) to prevent the base from inhibiting the reaction. As the catalyst is soluble in a polar solvent such as alcohol or water, the catalyst can only be recovered by extraction. After recycling for five times, the Pd content in these layers (organic layer and water layer) was measured by inductively coupled plasma-atomic emission spectroscopy. The quantification showed that 4% used Pd NPs-Cl or 9% Pd NPs-OAc was present in the organic layer. In the water layer, the corresponding values were determined to be 68% used Pd NPs-Cl or 58% Pd NPs-OAc. Therefore, Pd NPs were separated from the substrate and product only by the extraction procedure. The recovered Pd NPs were successfully recycled at least five times (Figure ). Furthermore, taking into account that the catalyst amount decreased by one order of magnitude (0.004 mol %), the yields obtained after recycling five times were high. The Pd NPs-OAc derived from the more readily reducible Pd precursor would provide a stable, catalytically active, and recyclable catalyst in this reaction.

Figure 4

Multiple catalyst recycling procedure for the Suzuki–Miyaura cross-coupling reaction.

Conclusions

In summary, the synthesis of DMF-protected Pd NPs (Pd NPs-OAc) from palladium acetate was successful and a detailed structural evaluation of the Pd NPs (−OAc and −Cl) was performed. The analysis revealed that the surface of both Pd NPs-OAc and −Cl was protected by DMF molecules. From ADF-STEM and DLS analysis, the particle size of Pd NPs-OAc was observed to be 3–5 nm. Catalytic studies demonstrated that an excellent TON (1.5 × 105) was achieved with Pd NPs-OAc. Pd NPs-OAc exhibit good recycling ability. The Suzuki–Miyaura cross-coupling reactions were successfully conducted in the presence of a new Pd NP-OAc catalyst.

Experimental Section

General

Gas liquid chromatography (GLC) analysis was performed using a flame ionization detector with a 0.22 nm × 25 m capillary column (BP-5). 1H and 13C NMR spectra were measured using JEOL JNM-ECS400 and JEOL JNM-ECZ400s spectrometers at 400 and 100 MHz, respectively, in CDCl3 with trimethylsilane as the internal standard. The products were characterized by 1H NMR, 13C NMR, and gas chromatography–mass spectrometry (GC-MS). All compounds 3a,[17a]3b,[17a]3c,[17a]3d,[17a]3e,[17b] 3f,[17c]3g,[17d]3h,[17b]3i,[17a]3j,[17a]3k,[17a]3l,[17a]3m,[17a] and 3n(17a) are known compounds, which have previously been reported. Pd precursors (e.g., Pd(OAc)2, PdCl2) were obtained from Tokyo Chemical Industry Co., Ltd. (TCI) and Wako Pure Chemical Industries, Ltd. (Wako). All solvents and other regents were obtained from Wako, TCI, and Sigma-Aldrich Co., LLC.

Preparation and Characterization of N,N-dimethylformamide (DMF)-Protected Palladium Nanoparticles (Pd NPs-Cl and Pd NPs-OAc)

Pd NPs-OAc derived from palladium acetate were synthesized by the DMF-protected method. Pd(OAc)2 (0.1123 g, 0.5 mmol) was dispersed in dehydrated acetic acid (10 mL), 0.05 M Pd(OAc)2 acetic acid solution. Preheated DMF (50 mL) at 140 °C was added to the Pd(OAc)2 acetic acid solution (200 μL) in a three-necked flask followed by heating at 140 °C for 10 h to yield a yellow solution containing Pd NPs-OAc.

Similarly, Pd NPs-Cl derived from palladium chloride were synthesized by the DMF-protected method. PdCl2 (0.1773 g, 1 mmol) was dispersed in distilled water (9 mL) and HCl (1 mL), 0.1 M PdCl2 solution. Preheated DMF (50 mL) at 140 °C was added to a 0.1 M PdCl2 solution (500 μL) in a three-necked flask followed by heating at 140 °C for 10 h to yield an orange solution containing Pd NPs-Cl.

Excess DMF was removed by vacuum evaporation to obtain the DMF-protected Pd NPs and the residues were redispersed in selected solvents (e.g. methanol, N-methylpyrroridone, and water) prior to using in the Suzuki–Miyaura cross-coupling reaction.

Annular Dark-Field Scanning Transmission Electron Microscopy (ADF-STEM)

ADF-STEM observations were performed using a JEOL JEM-ARM200F field emission microscope operating at 200 kV. A Cu microgrid was used.

Fourier Transform Infrared Spectroscopy (FT-IR)

FT-IR spectroscopy was performed on a SHIMADZU IRAffinity-1 Fourier transform infrared spectrophotometer. The dried DMF-protected Pd NPs were prepared under a vacuum of less than 0.1 hPa at room temperature for 1 day followed by dispersing over a NaCl crystal for the FT-IR measurements.

NMR Spectroscopy

The dried DMF-protected Pd NPs were prepared under a vacuum of less than 0.1 hPa at 100 °C for 1 day prior to NMR measurements.

XPS

XPS spectra of dried DMF-protected Pd NPs were measured using a ULVAC-PHI, PHI5000 VersaProbe instrument with Al Kα as the irradiation source (1400 eV). The binding energies were referenced to C1s at 284.6 eV.

Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES)

After recycling the catalysts, the Pd content in organic and water layers was measured using a Shimadzu ICP-8100 instrument.

Procedure for Suzuki–Miyaura Cross Coupling (Entry 6,Table )

A mixture of bromobenzene (1a, 0.0785 g, 0.5 mmol), 4-methylphenylboronic acid (2a, 0.1020 g, 0.75 mmol), and K2CO3 (0.1035 g, 0.75 mmol) were added to a pressure container followed by Pd NPs in methanol (0.2 mm, 1.0 mL) as the catalyst and water (1 mL). The reaction mixture was stirred at 100 °C for 16 h under argon. Substrate conversion and the product yield were calculated from their GC peak areas based on n-tridecane as the internal standard. The reaction mixture was extracted with distilled water and ethyl acetate to separate the product from the Pd NPs and K2CO3. The product (3a, 0.0819 g, 97%) was isolated by column chromatography (silica gel, n-hexane: ethyl acetate = 200:1 as eluent) as a white solid (m.p. 46–47 °C).

3a(17a)

Purification by silica gel chromatography (n-hexane: EtOAc = 200: 1) gave 3a (0.485 mmol, 97%) as a white solid (mp 46–47 °C, lit 46–47 °C); 1H NMR (400 MHz, CDCl3) δ: 7.58 (2H, dd, J = 8.2, 1.1 Hz), 7.49 (2H, d, J = 8.1 Hz), 7.42 (2H, t, J = 7.5 Hz), 7.33 (1H, d, J = 7.4 Hz), 7.25 (2H, d, J = 7.5 Hz), 2.39 (3H, s); 13C NMR (100 MHz, CDCl3) δ: 141.14 (C), 138.34 (C), 137.01 (C), 129.47 (CH), 128.70 (CH), 126.98 (CH), 21.10 (CH3).; GC–MS (EI) m/z (relative intensity) 168 (100) [M]+, 153(21), 115(7).

3b(17a)

Purification by silica gel chromatography (n-hexane: EtOAc = 200: 1) gave 3b (0.495 mmol, 99%) as a white solid (mp 109.2–110.8 °C, lit 111–112 °C); 1H NMR (400 MHz, CDCl3) δ: 7.51 (2H, d, J = 8.6 Hz), 7.45 (2H, d, J = 8.2 Hz), 7.23 (2H, t, J = 7.9 Hz), 6.96 (2H, d, J = 8.6 Hz), 3.84 (3H, s), 2.38 (3H, s); 13C NMR (100 MHz, CDCl3) δ: 158.94 (C), 137.99 (C), 136.35 (C), 133.77 (C), 129.43 (CH), 127.96 (CH), 126.59 (CH), 114.17 (CH), 55.35 (CH3), 21.05 (CH3); GC–MS (EI) m/z (relative intensity) 198 (100) [M]+, 183(57), 152(11).

3c(17a)

Purification by silica gel chromatography (n-hexane: EtOAc = 200: 1) yielded 3c (0.415 mmol, 83%) as a white solid (mp 102.6–103.2 °C, lit 103–104 °C); 1H NMR (400 MHz, CDCl3) δ: 10.05 (1H, s), 7.94 (2H, t, J = 4.2 Hz), 7.74 (2H, d, J = 8.2 Hz), 7.54 (2H, d, J = 8.0 Hz), 7.28 (2H, t, J = 8.6 Hz), 2.42 (3H, s); 13C NMR (100 MHz, CDCl3) δ: 191.88 (CH), 147.09 (C), 138.49 (C), 136.73 (C), 134.92 (C), 130.22 (CH), 129.71 (CH), 127.35 (CH), 127.15 (CH), 21.14 (CH3); GC–MS (EI) m/z (relative intensity) 196 (100) [M]+, 167(26), 152(48).

3d(17a)

Purification by silica gel chromatography (n-hexane: EtOAc = 200: 1) gave 3d (0.41 mmol, 82%) as a white solid (mp 121.4–122.8 °C, lit 121–122 °C); 1H NMR (400 MHz, CDCl3) δ: 7.67 (4H, s), 7.49 (2H, d, J = 8.2 Hz), 7.27 (2H, t, J = 4.2 Hz), 2.41 (3H, s); 13C NMR (100 MHz, CDCl3) δ: 144.67 (C), 138.16 (C), 136.89 (C), 129.73 (CH), 129.06 (C, q, J = 32.5 Hz), 127.18 (CH), 127.12 (CH), 125.68 (CH, q, J = 3.7 Hz), 124.37 (C q, J = 270.8 Hz), 21.14 (CH3); GC–MS (EI) m/z (relative intensity) 236(100) [M]+, 167(55), 152(11).

3e(17b)

Purification by silica gel chromatography (n-hexane: EtOAc = 200: 1) gave 3e (0.18 mmol, 36%) as colorless oil; 1H NMR (400 MHz, CDCl3) δ: 8.68 (1H, d, J = 4.7 Hz), 7.90–7.88 (m, 2H), 7.75–7.69 (m, 2H), 7.29–7.19 (m, 3H), 2.41 (3H, s); 13C NMR (100 MHz, CDCl3) δ: 157.4(C), 149.5(CH), 139.0(C), 136.8(C), 136.5(CH), 129.5(CH), 126.8(CH), 121.8(CH), 120.3(CH), 21.2(CH3); GC-MS (EI) m/z (relative intensity) 170(13), 169(100) [M]+, 168(64), 167(26), 154(8), 83(12).

3f(17c)

Purification by silica gel chromatography (n-hexane: EtOAc = 8: 1) gave 3f (0.45 mmol, 90%) as a white solid (mp 37.2–38.1 °C, lit 37–38 °C); 1H NMR (400 MHz, CDCl3) δ: 8.84 (1H, dd, J = 2.3, 0.7 Hz), 8.57 (1H, dd, J = 4.8, 1.6 Hz), 7.85 (1H, ddd, J = 7.9, 2.4, 1.7 Hz), 7.49–7.46 (2H, m), 7.35–7.25 (3H, m), 2.41 (3H, s); 13C NMR (100 MHz, CDCl3) δ: 148.15 (CH), 148.13 (CH), 138.04 (C), 136.59 (C), 134.91 (C), 134.16 (CH), 129.81 (CH), 126.98 (CH), 123.52 (CH), 21.14 (CH3); GC–MS (EI) m/z (relative intensity) 169(100) [M]+, 154(4), 142(4), 115 (21).

3g(17d)

Purification by silica gel chromatography (n-hexane) gave 3g (0.051 mmol, 10%) as a white solid (mp 68.0–69.0 °C, lit 60–64 °C); 1H NMR (400 MHz, CDCl3) δ: 7.50 (2H, d, J = 8.0 Hz), 7.27–7.17 (m, 4H), 7.10–7.05 (m, 1H), 2.36 (3H, s); 13C NMR (100 MHz, CDCl3) δ: 144.6(C), 137.3(C), 131.6(C), 129.5(CH), 127.9(CH), 125.9(CH), 124.2(CH), 122.6(CH), 21.2(CH3); GC–MS (EI) m/z (relative intensity) 175(14), 174(100)[M]+, 173(55), 141(12), 129(16), 128(13), 115(12).

3h(17b)

Purification by silica gel chromatography (n-hexane: EtOAc = 100: 1) gave 3h (0.475 mmol, 95%) as a white solid (mp 53.4–54.1 °C, lit 52–54 °C); 1H NMR (400 MHz, CDCl3) δ: 7.93–7.81 (3H, m), 7.51–7.27 (8H, m), 2.44 (3H, s); 13C NMR (100 MHz, CDCl3) δ: 140.22 (C), 137.79 (C), 136.88 (C), 133.79 (C), 131.69 (C), 129.93 (CH), 128.95 (CH), 128.22 (CH), 127.41 (CH), 126.86 (CH), 126.07 (CH), 125.89 (CH), 125.68 (CH), 125.37 (CH), 21.22 (CH3); GC–MS (EI) m/z (relative intensity) 218(100)[M]+, 217(30), 203(61), 202(51), 101(11).

3i(17a)

Purification by silica gel chromatography (n-hexane: EtOAc = 100: 1) gave 3i (0.42 mmol, 84%) as a white solid (mp 96.4–97.6 °C, lit 96–97 °C); 1H NMR (400 MHz; CDCl3) δ: 3.74 (s, 3H), 3.85 (d, J = 5.0 Hz, 4H), 5.12–5.20 (m, 4H), 5.80–5.89 (m, 2H), 6.68 (d, J = 9.1 Hz, 2H), 6.80 (d, J = 9.1 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 53.6 (CH2), 55.8 (CH3), 114.4 (CH), 114.6 (CH), 116.1 (CH2), 134.5 (CH), 143.5 (C), 151.5 (C); GC–MS (EI) m/z (relative intensity) 203 (100) [M]+, 176 (41), 135 (55), 91 (9), 77 (16).

3j(17a)

Purification by silica gel chromatography (n-hexane: EtOAc = 200: 1) gave 3j (0.4 mmol, 80%) as colorless oil; 1H NMR (400 MHz, CDCl3) δ: 3.74 (s, 3H), 3.85 (d, J = 5.0 Hz, 4H), 5.12–5.20 (m, 4H), 5.80–5.89 (m, 2H), 6.68 (d, J = 9.1 Hz, 2H), 6.80 (d, J = 9.1 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 53.6 (CH2), 55.8 (CH3), 114.4 (CH), 114.6 (CH), 116.1 (CH2), 134.5 (CH), 143.5 (C), 151.5 (C); GC–MS (EI) m/z (relative intensity) 203 (100) [M]+, 176 (41), 135 (55), 91 (9), 77 (16).

3k(17a)

Purification by silica gel chromatography (n-hexane: EtOAc = 200: 1) gave 3k (0.40 mmol, 86%) as a white solid (mp 76.3–77.8 °C, lit 76–78 °C); 1H NMR (400 MHz, CDCl3) δ: 3.74 (s, 3H), 3.85 (d, J = 5.0 Hz, 4H), 5.12–5.20 (m, 4H), 5.80–5.89 (m, 2H), 6.68 (d, J = 9.1 Hz, 2H), 6.80 (d, J = 9.1 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 53.6 (CH2), 55.8 (CH3), 114.4 (CH), 114.6 (CH), 116.1 (CH2), 134.5 (CH), 143.5 (C), 151.5 (C); GC–MS (EI) m/z (relative intensity) 203 (100) [M]+, 176 (41), 135 (55), 91 (9), 77 (16).

3l(17a)

Purification by silica gel chromatography (n-hexane: EtOAc = 200: 1) gave 3l (0.5 mmol, 99%) as a white solid (mp 85.7–86.7 °C, lit 84–86 °C); 1H NMR (400 MHz, CDCl3) δ: 3.74 (s, 3H), 3.85 (d, J = 5.0 Hz, 4H), 5.12–5.20 (m, 4H), 5.80–5.89 (m, 2H), 6.68 (d, J = 9.1 Hz, 2H), 6.80 (d, J = 9.1 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 53.6 (CH2), 55.8 (CH3), 114.4 (CH), 114.6 (CH), 116.1 (CH2), 134.5 (CH), 143.5 (C), 151.5 (C); GC–MS (EI) m/z (relative intensity) 203 (100) [M]+, 176 (41), 135 (55), 91 (9), 77 (16).

3m(17a)

Purification by silica gel chromatography (n-hexane: EtOAc = 200: 1) gave 3m (0.395 mmol, 79%) as a white solid (mp 68.4–69.4 °C, lit 67–68 °C); 1H NMR (400 MHz, CDCl3) δ: 7.69 (4H, s), 7.60–7.59 (2H, m), 7.47–7.42 (3H, m); 13C NMR (100 MHz, CDCl3) δ 144.8(C, d,4JC-F = 1.2 Hz), 139.8(C), 129.4(C, q,2JC-F = 32.3 Hz), 129.0(CH), 128.2(CH), 127.4(CH), 127.3(CH), 125.7(CH, q,3JC-F = 3.9 Hz), 124.3(CF3, q,1JC-F = 271.3 Hz); GC–MS (EI) m/z (relative intensity) 223(14), 222(100) [M]+, 203(7), 201(9), 153(19), 152(21), 151(6), 86(5).

3n(17a)

Purification by silica gel chromatography (n-hexane: EtOAc = 100: 1, 7: 3) gave 3n (0.485 mmol, 97%) as a white solid (mp 119.0–119.7 °C, lit 119–120 °C); 1H NMR (400 MHz, CDCl3) δ: 8.03 (2H, d, J = 8.3 Hz), 7.69 (d, 2H, J = 8.3 Hz), 7.63 (d, 2H, J = 7.2 Hz), 7.49–7.38 (m, 3H), 2.64 (3H, s); 13C NMR (100 MHz, CDCl3,) δ: 197.7(C), 145.8(C), 139.9(C), 135.9(C), 129.0(CH), 128.9(CH), 128.2(CH), 127.3(CH), 127.2(CH), 26.7(CH3); GC–MS (EI) m/z (relative intensity) 196 (59) [M]+, 181 (100), 153 (45), 152 (58), 151 (17), 76 (18).