HETEROCYCLES

Paper | Regular issue | Vol. 83, No. 4, 2011, pp. 827-835
Received, 21st January, 2011, Accepted, 21st February, 2011, Published online, 2nd March, 2011.
DOI: 10.3987/COM-11-12146

■ Heck-Mizoroki Reaction of 4-Iodo-1H-pyrazoles

Yoshihide Usami,* Hayato Ichikawa, and Shinya Harusawa

Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Abstract

The Heck-Mizoroki reaction of 1-protected-4-iodo-1H-pyrazoles with various kinds of alkenes was examined and found to yield 1-protected-4-alkenyl-1H-pyrazoles. P(OEt)3 was a suitable ligand for the cross-coupling reaction, together with the trityl group that acted as an appropriate protecting group of 1H-pyrazole.

INTRODUCTION
The exploration of new methods for the synthesis of heterocyclic compounds is an important work for synthetic organic chemists, as most drugs or bioactive compounds possess one or more heterocyclic moieties in their molecules. Pyrazoles are one of the most important classes of heterocyclic compounds1,2 and many pyrazole syntheses are based on the construction of a pyrazole ring by cycloaddition of hydrazines with 1,3-dicarbonyl compounds or diazomethane with acetylenes in the last step. A novel binuclear platinum(II) complex bearing 4-methylpyrazole (4mpz)3 as the ligand showed enhanced antitumor activity in the cisplatin-resistant L1210/R cell line. The discovery of the 4mpz ligand encouraged us to develop practical cross-coupling methods for the synthesis of novel C-4 substituted pyrazoles. We have so far reported the synthesis of 4-arylpyrazoles by the Kumada coupling (Scheme 1, eq. 1)4 or the Suzuki-Miyaura coupling (eq. 2),5 and the synthesis of 4-alkynylpyrazoles by the Sonogashira coupling (eq. 3), which further provided 2H-indazoles by the double Sonogashira coupling of bisiodo-1H-pyrazoles followed by the Bergman-Masamune cycloaromatization.6 As an extension of our synthetic studies of 4-functionalized 1H-pyrazoles, we next addressed the Heck-Mizoroki reaction, which is widely applied to the preparation of substituted alkenes by the cross-coupling reaction between alkenyl compounds and arylhalides or aryltriflates in the presence of palladium(0) catalysts.7-9 Ying and co-workers reported the Heck-Mizoroki reaction between 4-bromo-1,3,5-trimethylpyrazole and tert-butyl acrylate in the presence of IMes-Pd(dmba)Cl (4 mol %) in the development of a new Pd catalyst, but the yield was only 32%.10 As far as we know, this is the only example of the Heck-Mizoroki reaction of 4-halopyrazole.10-12 In this article, we describe the direct alkenylation of 4-iodo-1H-tritylpyrazole (1a) using the Heck-Mizoroki reaction.

RESULTS AND DISCUSSION
We first examined the Heck-Mizoroki reaction of 4-iodo-1H-tritylpyrazole (1a) with methyl acrylate in the presence of Pd(OAc)2 (1 mol %), phosphine ligand, and triethylamine in DMF at 80 oC for 24 h. The results are summarized in Table 1. In the absence of the phosphine ligand, 4-(2-methoxycarbonylvinyl)-1-trityl-1H-pyrazole (2a) was obtained in only 46% yield (entry 1). 2a was assigned the E-configuration from the coupling constant (15.9 Hz) between the double bond protons in the 1H-NMR spectrum. Use of P(OEt)3 (4 mol %) as a ligand improved the yield of 2a to 95% (entry 4), whereas higher concentrations of P(OEt)3 lowered the yield (entries 2 and 3). Reducing the amount of methyl acrylate from 5 to 1.2 equivalent in the presence of 4 mol % of P(OEt)3 afforded 2a in 95% yield (entry 5). Changing the ligand from P(OEt)3 to PPh3 decreased the yield to 50% (entry 6), and increasing the amount of Pd(OAc)2 from 1 to 10 mol % had little effect on the yield (entry 7). From these results, we adopted the reaction conditions of entry 5 as the general procedure for further studies.
To clarify the scope and limitations of the Heck-Mizoroki reaction of 1, the reactions of various 1-protected 4-iodo1H-pyrazoles 1a-f with alkenes were carried out using the previous reaction conditions (Table 1, entry 5), and the results are summarized in Table 2. From the results of entries 1-6 in Table 2, the trityl group was confirmed to be a desirable N-1 protective group and benzyl groups were also an acceptable protective group (entry 2). In the cases of p-toluenesulfonyl and 2,4,6-trimethylbenzoyl groups

(entries 3 and 4), the corresponding products (E)-2c and 2d were obtained in modest yields, whereas Boc- and Cbz-substituted carbamates 1e and 1f were unfavorable as an N-1 protective group (entries 5 and 6). We next focused on the reaction of 1a with various alkenes (entries 7-18). tert-Butyl acrylate and methyl vinyl ketone were good coupling partners of 1a, affording 2g and 2h in 90% and 85% yields, respectively (entries 7 and 8). Although most of the coupling reactions afforded selectively E-alkene products, the reactions of 1a with methyl vinyl ketone (entry 8) or acrylonitrile (entry 13) gave a mixture of E- and Z-isomers. The reactions of 1a with vinyl acetate (entry 10), acrolein (entry 11), diethyl vinylphosphonate (entry 12), or acrylonitrile (entry 13) gave Heck products in low yields, accompanied by starting material 1a or dehalogenated 1-tritylpyrazole 3.
Although the reactions of 1a with some styrenes were examined (entries 14-17), the reactions gave (E)-2n-q in low yields. Increasing the amounts of Pd(OAc)2 and P(OEt)3 in the reaction of 1a with styrene improved somewhat the yield (entry 18). The results in Table 2 indicated the scope and limitations of our procedure for the direct C-4 alkenylation of 1-protected -1H-pyrazoles via the Heck-Mizoroki reaction.

CONCLUSION
The synthesis of 1-protected-4-alkenyl-1H-pyrazoles from 1-protected-4-iodo-1H-pyrazoles using the Heck-Mizoroki reaction was investigated. The results indicated that P(OEt)3, trityl group, and acrylates were appropriate for use as a ligand, a protective group, and coupling partner in this reaction, respectively. This study offered a new aspect in the direct functionalization of pyrazoles.

EXPERIMENTAL
Unless otherwise indicated, all starting materials were obtained from commercial suppliers (Aldrich, Kishida Chemical, Nacalai Tesque, Wako Pure Chemicals, and TCI) and used without further purification. IR spectra were obtained with a JEOL FT/IR-680 Plus spectrometer. HRMS was determined with a JEOL JMS-700 (2) mass spectrometer. NMR spectra were recorded at 27 oC on Varian UNITY INOVA-500 and Mercury-300 spectrometers in CDCl3 with tetramethylsilane (TMS) as the internal standard. Melting points were determined on a Yanagimoto micromelting point apparatus and are uncorrected. Liquid column chromatography was conducted over silica gel (SiliCycle, SiliaFlash F60, 40-63 µm). Analytical TLC was performed on precoated Merck glass plates (silica gel 60 F254) and compounds were detected by dipping the plates in an ethanol solution of phosphomolybdic acid, followed by heating.

Typical synthetic procedure (Table 1, entry 5): 4-Iodo-1H-tritylpyrazole (1a) (0.44 g, 1.0 mmol) and Pd(OAc)2 (2.2 mg, 0.01 mmol) were dissolved in DMF (6 mL). The resulting solution was added dropwise to a mixture of Et3N (1.2 mL), P(OEt)3 (6.9 µL, 0.04 mmol), and methyl acrylate (108 µL, 1.2 mmol). The reaction mixture was heated to 80 °C with stirring for 24 h under nitrogen atmosphere and the resulting mixture was poured into water and extracted with CH2Cl2. The organic layer was washed with brine, dried over MgSO4, filtered, and evaporated to furnish a crude product that was purified by silica gel column chromatography (eluent: hexane/EtOAc = 4:1) to give 2a (0.36 g, 95%).
4-(2-Methoxycarbonylvinyl)-1-trityl-1H-pyrazole (2a): Colorless needles (CH2Cl2); mp 196−199 °C; IR (KBr) νmax 1699 (C=O), 1643 (C=C), 1493 (C=C) cm−1; 1H-NMR (300 MHz, CDCl3): δ 7.87 (1H, s, pyrazole-H), 7.55 (1H, s, pyrazole-H), 7.53 (1H, d, J = 15.9 Hz, -CH=CH-), 7.38–7.27 (9H, m, Tr-H), 7.20–7.12 (6H, m, Tr-H), 6.14 (1H, d, J = 15.9 Hz, -CH=CH-), 3.78 (3H, s, COOCH3); 13C-NMR (75 MHz, CDCl3): δ 167.6, 142.6, 138.8, 135.4, 132.8, 130.0, 128.0, 127.9, 116.9, 115.6, 79.1, 51.5; HRMS m/z calcd for C26H22N2O2 (M+) 394.1682, found 394.1673.
1-Benzyl-4-(2-methoxycarbonylvinyl)-1H-pyrazole (2b): Colorless needles; mp 68 °C; IR (KBr) νmax 1707 (C=O), 1637 (C=C) cm-1; 1H-NMR (300 MHz, CDCl3): δ 7.73 (1H, s, pyrazole-H), 7.54 (1H, d, J = 16.0 Hz, -CH=CH-), 7.536 (1H, s, pyrazole-H), 7.36–7.32 (2H, m Ph-H), 7.24–7.21 (2H, m, Ph-H), 6.15 (1H, d, J = 16.0 Hz, -CH=CH-), 5.28 (2H, s, NCH2Ph), 3.75 (3H, s, -COOCH3); 13C-NMR (75 MHz, CDCl3): δ 167.6, 138.8, 135.6, 135.1, 129.5, 128.9, 128.3, 127.8, 118.6, 115.5, 56.2, 51.4; HRMS m/z calcd for C14H14N2O2 (M+) 242.1055, found 242.1054.
4-(2-Methoxycarbonylvinyl)-1-tosyl-1H-pyrazole (2c): Colorless needles (CH2Cl2); mp 159−160 °C; IR (KBr) νmax 1716 (C=O), 1648 (C=C), 1588 (C=C) cm−1; 1H-NMR (300 MHz, CDCl3): δ 8.22 (1H, s, pyrazole-H), 7.91 (2H, d, J = 8.2 Hz, Ts-H), 7.87 (1H, s, pyrazole-H), 7.49 (1H, d, J = 16.1 Hz, -CH=CH-), 7.34 (2H, d, J = 8.2 Hz, Ts-H), 6.24 (1H, d, J = 16.1 Hz, -CH=CH-), 3.76 (3H, s, -COOCH3), 2.42 (3H, s, -PhCH3); 13C-NMR (75 MHz, CDCl3): δ 166.8, 146.4, 143.3, 133.3, 132.9, 130.4, 130.2, 128.3, 120.6, 119.3, 51.7, 21.7; HRMS m/z calcd for C14H14N2O4S (M+) 306.0674, found 306.0670.
4-(2-Methoxycarbonylvinyl)-1-(2,4,6-trimethylbenzoyl)-1H-pyrazole (2d): Colorless crystals (CH2Cl2); mp 134−136 °C; IR (KBr) νmax 1725 (C=O), 1712 (C=O), 1645 (C=C), 1609 (C=C) cm−1; 1H-NMR (300 MHz, CDCl3): δ 8.50 (1H, br s, pyrazole-H), 7.89 (1H, s, pyrazole-H), 7.58 (1H, d, J = 16.1 Hz, -CH=CH-), 6.93 (2H, s, Ar-H), 6.33 (1H, d, J = 16.1 Hz, -CH=CH-), 3.80 (3H, s, COOCH3), 2.33 (3H, s, ArCH3), 2.15 (6H, s, 2x ArCH3); 13C-NMR (75 MHz, CDCl3): δ 166.9, 143.2, 140.2, 134.7, 133.1, 130.4, 128.2, 121.7, 119.6, 116.3, 56.2, 51.7, 21.2, 19.1; HRMS m/z calcd for C17H18N2O3 (M+) 298.1317, found 298.1307.
4-(2-Methoxycarbonylvinyl)-1H-pyrazole (2e): Colorless needles (CH2Cl2); mp 92−95 °C; IR (KBr) νmax 1731 (C=O), 1649 (C=C) cm−1; 1H-NMR (300 MHz, CDCl3): δ 9.00 (1H, br s, NH), 7.80 (2H, s, pyrazole-H), 7.62 (1H, d, J = 15.9 Hz, -CH=CH-), 6.22 (1H, d, J = 15.9 Hz, -CH=CH-), 3.78 (3H, s, COOCH3); 13C-NMR (75 MHz, CDCl3): δ 167.7, 135.2, 133.7, 117.9, 116.1, 51.6; HRMS m/z calcd for C7H8N2O2 (M+) 152.0586, found 152.0582.
4-(2-tert-Butoxycarbonylvinyl)-1-trityl-1H-pyrazole (2g): Colorless crystals (CH2Cl2); mp 148−152 °C; IR (KBr) νmax 1704 (C=O), 1638 (C=C), 1499 (C=C) cm−1; 1H-NMR (300 MHz, CDCl3): δ 7.88 (1H, s, pyrazole-H), 7.57 (1H, s, pyrazole-H), 7.46 (1H, d, J = 15.9 Hz, -CH=CH-), 7.37–7.28 (9H, m, Tr-H), 7.22–7.16 (6H, m, Tr-H), 6.13 (1H, d, J = 15.9 Hz, -CH=CH-), 1.53 (9H, s, -tBu); 13C-NMR (75 MHz, CDCl3): δ 166.4, 142.6, 138.7, 133.9, 132.5, 130.0, 127.8, 127.1, 118.0, 117.0, 80.0, 79.0, 28.1; HRMS m/z calcd for C29H28N2O2 (M+) 436.2151, found 436.2147.
4-[3-Oxo-(E)-1-butenyl]-1-trityl-1H-pyrazole [(E)-2h]: Colorless needles (CH2Cl2); mp 214−216 °C; IR (KBr) νmax 1667 (C=O), 1625 (C=C), 1541 (C=C) cm−1; 1H-NMR (300 MHz, CDCl3): δ 7.89 (1H, s, pyrazole-H), 7.59 (1H, s, pyrazole-H), 7.37 (1H, d, J = 16.8 Hz, -CH=CH-), 7.34–7.31 (9H, m, Tr-H), 7.25–7.13 (6H, m, Tr-H), 6.43 (1H, d, J = 16.8 Hz, -CH=CH-), 2.28 (3H, s, CH3); 13C-NMR (75 MHz, CDCl3): δ 198.1, 142.4, 138.9, 134.1, 133.0, 130.0, 128.0, 127.9, 127.8, 125.6, 79.2, 27.0; HRMS m/z calcd for C26H22N2O (M+) 378.1732, found 378.1734.
4-(3-Oxo-(Z)-1-butenyl)-1-trityl-1H-pyrazole ((Z)-2h): Colorless crystals (CH2Cl2); mp 163−166 °C; IR (KBr) νmax 1676 (C=O), 1580 (C=C), 1541 (C=C) cm−1; 1H-NMR (300 MHz, CDCl3): δ 8.47 (1H, s, pyrazole-H), 8.09 (1H, s, pyrazole-H), 7.40–7.27 (9H, m, Tr-H), 7.25–7.13 (6H, m, Tr-H), 6.55 (1H, d, J = 8.2 Hz, -CH=CH-), 6.07 (1H, d, J = 8.2 Hz, -CH=CH-), 2.22 (3H, s, CH3); 13C-NMR (75 MHz, CDCl3): δ 197.5, 143.4, 142.6, 136.3, 131.9, 130.0, 127.8, 121.4, 116.7, 79.0, 31.3 (lack of a carbon signal probably because of overlap with one of the other aromatic carbon signals); HRMS m/z calcd for C26H22N2O (M+) 378.1732, found 378.1724.
4-(2-Morphorylcarbonylvinyl)-1-trityl-1H-pyrazole (2i): White powder (CH2Cl2); mp 138−141 °C; IR (KBr) νmax 1649 (C=O), 1601 (C=C) cm-1; 1H-NMR (300 MHz, CDCl3): δ 7.87 (1H, s, pyrazole-H), 7.55 (1H, d, J = 15.4 Hz, -CH=CH-), 7.54 (1H, s, pyrazole-H), 7.34−7.29 (9H, m, Tr-H), 7.18−7.12 (6H, m, Tr-H), 6.56 (1H, d, J = 15.4 Hz, -CH=CH-), 3.68 (4H,br s), 3.676 (4H, br s); 13C-NMR (75 MHz, CDCl3): δ 165.7, 142.6, 138.3, 133.7, 132.7, 130.0, 127.9, 127.8, 117.6, 114.2, 79.0, 66.8 (lack of a carbon signal probably because of overlap with the carbon signal at 66.8 ppm); HRMS m/z calcd for C29H27N3O2 (M+) 449.2103, found 449.2100.
1-Trityl-4-vinyl-1H-pyrazole (2j): Colorless crystals (CH2Cl2); mp 127−130 °C; IR (KBr) νmax 1641 (C=C), 1491 (C=C) cm−1; 1H-NMR (300 MHz, CDCl3): δ 7.77 (1H, s, pyrazole-H), 7.36 (1H, s, pyrazole-H), 7.34–7.30 (9H, m, Tr-H), 7.26–7.12 (6H, m, Tr-H), 6.46 (1H, dd, J = 17.7, 11.0 Hz, -CH=CHH), 5.43 (1H, d, J = 17.7 Hz, -CH=CHtransH), 5.04 (1H, d, J = 11.0 Hz, -CH=CHHcis); 13C-NMR (75 MHz, CDCl3): δ 143.0, 137.3, 130.0, 127.9, 127.7, 126.8, 119.6, 111.9, 78.5 (lack of a carbon signal probably because of overlap with one of the other aromatic carbon signals); HRMS m/z calcd for C24H20N2 (M+) 336.1626, found 336.1620.
4-(2-Formylvinyl)-1-trityl-1H-pyrazole (2k): Pale yellow powder (CH2Cl2); mp 211−213 °C; IR (KBr) νmax 1716 (C=O), 1676 (C=C), 1634 (C=C) cm-1; 1H-NMR (300 MHz, CDCl3): δ 9.52 (1H, d, J = 7.9 Hz, -CHO), 7.91 (1H, s, pyrazole-H), 7.64 (1H, s, pyrazole-H), 7.34−7.14 (16H, m, Tr-H, -CH=CHCHO), 6.42 (1H, dd, J = 15.7, 7.0 Hz, -CH=CHCHO); 13C-NMR (75 MHz, CDCl3): δ 193.4 (193.3), 143.4, 142.3, 139.3 (138.9), 133.4 (133.2), 130.0, 129.9, 127.9, 126.8, 116.9, 79.3; HRMS m/z calcd for C25H20N2O (M+) 364.1576, found 364.1580.
4-{2-(P,P-Diethoxyphosphonyl)vinyl}-1-trityl-1H-pyrazole (2l): Colorless crystals (CH2Cl2); mp 97−100 °C; IR (KBr) νmax 1621 (C=C) cm-1; 1H-NMR (300 MHz, CDCl3): δ 7.84 (1H, s, pyrazole-H), 7.52 (1H, s, pyrazole-H), 7.40–7.25 (9H, m, Tr-H), 7.18–7.11 (6H, m, Tr-H), 5.92 (1H, d, J = 18.0 Hz, -CH=CH-), 5.87 (1H, d, J = 18.0 Hz, -CH=CH-), 4.10 (2H, q, J = 7.1 Hz, -PO(OCH2CH3)OEt), 4.07 (2H, q, J = 7.1 Hz, -PO(OCH2CH3)OEt), 1.33 (6H, t, J = 7.1 Hz, -PO(OCH2CH3)2); 13C-NMR (75 MHz, CDCl3): δ 142.5, 139.4 (d, 2JC-P = 6.9 Hz), 138.4, 132.5, 130.0, 127.8, 127.1, 117.8 (d, 3JC-P = 25.2 Hz), 110.1 (d, 1JC-P = 194 Hz), 79.1, 61.7 (d, 2JC-P = 4.6 Hz), 16.3 (d, 3JC-P = 5.7 Hz); HRMS m/z calcd for C28H29N2O3P (M+) 472.1916, found 472.1918.
4-[(E)-2-Cyanovinyl]-1-trityl-1H-pyrazole ((E)-2m): Colorless needles (EtOAc-hexane); mp 233−236 °C; IR (KBr) νmax 2214 (CN), 1629 (C=C), 1597 (C=C) cm-1; 1H-NMR (300 MHz, CDCl3): δ 7.84 (1H, s, pyrazole-H), 7.55 (1H, s, pyrazole-H), 7.38−7.28 (9H, m, Tr-H), 7.21 (1H, d, J = 16.6 Hz, -CH=CH-), 7.18−7.10 (6H, m, Tr-H), 5.55 (1H, d, J = 16.6 Hz, -CH=CH-); 13C-NMR (75 MHz, CDCl3): δ 142.3, 141.0, 138.0, 132.6, 130.0, 128.1, 127.9, 118.5, 116.6, 93.5, 79.3; HRMS m/z calcd for C25H19N3 (M+) 361.1579, found 361.1576.
4-[(Z)-2-Cyanovinyl]-1-trityl-1H-pyrazole [(Z)-2m]: colorless crystals (CH2Cl2); mp 182−185 °C; IR (KBr) νmax 2211 (CN), 1615 (C=C), 1492 (C=C) cm-1; 1H-NMR (300 MHz, CDCl3): δ 8.14 (1H, s, pyrazole-H), 7.96 (1H, s, pyrazole-H), 7.38−7.28 (9H, m, Tr-H), 7.18−7.10 (6H, m, Tr-H), 6.96 (1H, d, J = 11.7 Hz, -CH=CH-), 5.15 (1H, d, J = 11.7 Hz, -CH=CH-); 13C-NMR (75 MHz, CDCl3): δ 142.4, 140.1, 139.5, 133.5, 130.0, 127.9, 127.2, 118.2, 116.2, 91.6, 79.4; HRMS m/z calcd for C25H19N3 (M+) 361.1579, found 361.1570.
4-(2-Phenylvinyl)-1-trityl-1H-pyrazole (2n): Colorless crystals (CH2Cl2); mp 225−228 °C; IR (KBr) νmax 1643 (C=C), 1490 (C=C) cm−1; 1H-NMR (500 MHz, CDCl3): δ 7.86 (1H, s, pyrazole-H), 7.46 (1H, s, pyrazole-H), 7.39 (2H, br d, J = 7.1 Hz, Ph-H), 7.35–7.25 (12H, m, Tr-H, Ph-H), 7.22–7.16 (6H, m, Tr-H), 6.90 (1H, d, J = 16.5 Hz, -CH=CH-), 6.80 (1H, d, J = 16.5 Hz, -CH=CH-); 13C-NMR (125 MHz, CDCl3): δ 143.5, 137.6, 130.4, 130.4, 130.1, 128.6, 127.9, 127.8, 127.6, 127.0, 125.8, 119.3, 118.7, 78.7; HRMS m/z calcd for C30H24N2 (M+) 412.1939, found 412.1940.
4-[2-(4-Fluorophenyl)vinyl]-1-trityl-1H-pyrazole (2o): Colorless needles (CH2Cl2); mp 239−242 °C; IR (KBr) νmax 1641 (C=C), 1507 (C=C) cm−1; 1H-NMR (500 MHz, CDCl3): δ 7.85 (1H, s, pyrazole-H), 7.45 (1H, s, pyrazole-H), 7.38–7.31 (11H, m, Tr-H, Ph-H), 7.22–7.15 (6H, m, Tr-H), 7.01 (1H, d, J = 8.7 Hz, Ph-H), 6.97 (1H, d, J = 8.6 Hz, Ph-H), 6.83 (1H, d, J = 16.6 Hz, -CH=CH-), 6.73 (1H, d, J = 16.6 Hz, -CH=CH-); 13C-NMR (125 MHz, CDCl3): δ 143.0, 137.5, 130.4, 130.1, 130.0, 127.9, 127.8, 127.4, 127.3, 119.2, 115.5 (d,2JC-F = 22.0 Hz), 78.7 (lack of a carbon signal probably because of overlap with one of the other aromatic carbon signals); HRMS m/z calcd for C30H23FN2 (M+) 430.1845, found 430.1848.
4-[2-(4-Nitrophenyl)vinyl]-1-trityl-1H-pyrazole (2p): Yellow plates (CH2Cl2); mp 163−168 °C; IR (KBr) νmax 1637 (C=C), 1593 (C=C), 1509 (NO2), 1342 (NO2) cm−1; 1H-NMR (300 MHz, CDCl3): δ 8.09 (2H, d, J = 8.8 Hz, -PhNO2), 7.83 (1H, s, pyrazole-H), 7.46 (1H, s, pyrazole-H), 7.41 (2H, d, J = 8.8 Hz, 　-PhNO2), 7.28–7.04 (15H, m, Tr-H), 7.01 (1H, d, J = 16.6 Hz, -CH=CH-), 6.75 (1H, d, J = 16.6 Hz, -CH=CH-); 13C-NMR (75 MHz, CDCl3): δ 142.8, 137.8, 131.4, 130.1, 129.0, 128.2, 127.9, 127.8, 126.1, 125.3, 124.5, 124.1, 118.6, 79.0; HRMS m/z calcd for C30H23N3O2 (M+) 457.1790, found 457.1786.
4-[1-(Pyridin-2-yl)vinyl]-1-trityl-1H-pyrazole (2q): White powder; mp 165−168 °C; IR (KBr) νmax 1636 (C=C), 1585 (C=C) cm-1; 1H-NMR (300 MHz, CDCl3): δ 8.53 (1H, br d, J = 4.6 Hz, pyridinyl-H), 7.91 (1H, s, pyrazole-H), 7.69 (1H, m, pyridinyl-H), 7.55 (1H, s, pyrazole-H), 7.50 (1H, d, J = 16.1 Hz, -CH=CH-), 7.38–7.10 (17H, m, Tr-H, pyridinyl-H), 6.88 (1H, d, J = 16.1 Hz, -CH=CH-); 13C-NMR (75 MHz, CDCl3): δ 143.1, 142.8, 142.0, 138.2, 136.2, 134.6, 131.8, 130.2, 130.1, 128.0, 127.75, 121.6, 121.5, 118.6, 78.9; HRMS m/z calcd for C29H23N3 (M+) 413.1982, found 413.1887.

ACKNOWLEDGEMENTS
We are grateful to Ms. Mihoyo Fujitake of this University for MS measurement and Professor Masao Arimoto, who retired from this University in 2009, for continuous encouragement. We thank Ms. Megumi Ashino of Nihon University for experimental assistance during her internship program, as well as Ms. Tomoko Matsushita and Mr. Yudai Suzuki of our laboratory. This work was supported in part by a Grant-in-Aid for the “High-Tech Research Center” Project for Private Universities: matching fund subsidy from MEXT (Ministry of Education, Culture, Sports, Science, and Technology), 2006−2009, Japan and the Lonza Japan Award 2009 in Synthetic Organic Chemistry, Japan to H. I.

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