Efficient C-7 or C-3/C-7 Direct Arylation of Tri- or Disubstituted Imidazo[1,2-b]pyrazoles

Sandrine Grosse; Christelle Pillard; Philippe Bernard; Gérald Guillaumet

doi:10.1055/s-0033-1339657

Synlett, Table of Contents

Synlett 2013; 24(16): 2095-2101
DOI: 10.1055/s-0033-1339657

letter

Efficient C-7 or C-3/C-7 Direct Arylation of Tri- or Disubstituted Imidazo[1,2-b]pyrazoles

Sandrine Grosse

^aInstitut de Chimie Organique et Analytique (ICOA), Université d’Orléans, UMR-CNRS 7311, BP 6759, rue de Chartres, 45067 Orléans cedex 2, France Fax: +33(38)417281 Email: gerald.guillaumet@univ-orleans.fr

,

Christelle Pillard

^bGreenpharma S.A.S, 3, allée du Titane, 45100 Orléans, France

,

Philippe Bernard

^bGreenpharma S.A.S, 3, allée du Titane, 45100 Orléans, France

,

Gérald Guillaumet*

^aInstitut de Chimie Organique et Analytique (ICOA), Université d’Orléans, UMR-CNRS 7311, BP 6759, rue de Chartres, 45067 Orléans cedex 2, France Fax: +33(38)417281 Email: gerald.guillaumet@univ-orleans.fr

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Abstract

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Abstract

A novel and efficient method of C-7 direct arylation of the imidazo[1,2-b]pyrazole core, never described to date, is presented in this paper. Series of electron-rich or electron-poor aryl and heteroaryl groups were easily introduced. The corresponding products were obtained in moderate to excellent yields thanks to this pallado-catalyzed and microwave-assisted process. A one-pot double C-3 and C-7 direct coupling is also reported.

Key words

C–C coupling - arylation - fused-ring systems - microwave chemistry - palladium

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References

References and Notes

1a Baviskar AT, Madaan C, Preet R, Mohapatra P, Jain V, Agarwal A, Guchhait SK, Kundu CN, Banerjee UC, Bharatam PV. J. J. Med. Chem. 2011; 54: 5013
1b Zhang J, Singh R, Goff D, Kinoshita T. U.S. Patent US20100316649(A1), 2010 ; Chem. Abstr. 2010, 154, 64825
1c Keshi O, Bahar I, Jernigan RL, Beutler JA, Shoemaker RH, Sansville EA, Covell DG. Anti-Cancer Drugs 2000; 15: 79
1d Kinnamon KE, Engle RR, Poon BT, Ellis WY, MacCall JW, Pzimianski MT. Proc. Soc. Exp. Biol. Med. 2000; 224: 45

2a Abdelhamid AO, Abdelall EK. A, Zakic YH. J. Heterocycl. Chem. 2010; 47: 477
2b Li M, Zhao G, Wen L, Cao W, Zhang S, Yang H. J. Heterocycl. Chem. 2005; 42: 209
2c Chen YF, Huang NY, Ding MW. Chin. J. Chem. 2004; 24: 1413

3 Terada A, Wachi K, Myazawa H, Lizuka Y, Hagesawa K, Tabata K. (Sankyo Co) Jpn. Patent 07278148, 1995 ; Chem. Abstr. 1996, 124, 8700

4a Bhatia G, Graczyk P, Khan A, Medland DP, Numata H, Oinuma H, Palmer V. Int. Patent WO02081475A1, 2002 ; Chem. Abstr. 2002, 137, 310918
4b Vanotti E, Fiorentini F, Villa M. J. Heterocycl. Chem. 1994; 31: 737

5a Rahmati A, Eskandari-Vashareh M, Alizadeh-Kouzehrash M. Tetrahedron 2013; 69: 4199
5b Rahmati A, Alizadeh-Kouzehrash M. Synthesis 2011; 2913
5c Shawali AS, Mosseelhi MA, Altablawy FM. A, Farghaly TA. F, Tawfik NM. Tetrahedron 2008; 64: 5524
5d Barsy MA, El-Rady EA. J. Heterocycl. Chem. 2006; 43: 523
5e Ming L, Guilong Z, Lirong W, Huazheng Y. Synth. Commun. 2005; 35: 493
5f Shawali AS, Abdelkader MH, Eltalbawy FM. A. Tetrahedron 2002; 58: 2875
5g Langer P, Wuckelt J, Döring M, Schreiner PR, Görls H. Eur. J. Org. Chem. 2001; 2257
5h Seneci P, Nicola M, Inglesi M, Vanotti E, Resnati G. Synth. Commun. 1999; 29: 311
5i Cho N, Kubo K, Furuya S, Sugiura Y, Yasuma T, Kohara Y, Ojima M, Inada Y, Nishikawa K, Naka T. Bioorg. Med. Chem. Lett. 1994; 4: 35
5j Hammouha HA, El-Barbary AA, Sharaf MA. F. J. Heterocycl. Chem. 1984; 21: 945
5k Wood SG, Dalley NK, George RD, Robins RK, Revankar GR. J. Org. Chem. 1984; 49: 3534
5l Hiroshi K, Masaaki H, Toshihiko O. Chem. Pharm. Bull. 1974; 22: 482

6 Grosse S, Pillard C, Massip S, Léger JM, Jarry C, Bourg S, Bernard P, Guillaumet G. Chem. Eur. J. 2012; 18: 14943

7a Bassoude I, Berteina-Raboin S, Massip S, Leger JM, Jarry C, Essassi EM, Guillaumet G. Eur. J. Org. Chem. 2012; 2572
7b El Akkaoui A, Berteina-Raboin S, Mouaddib A, Guillaumet G. Eur. J. Org. Chem. 2010; 862
7c Koubachi J, El Kazzouli S, Berteina-Raboin S, Mouaddib A, Guillaumet G. J. Org. Chem. 2007; 72: 7650
7d Koubachi J, El Kazzouli S, Berteina-Raboin S, Mouaddib A, Guillaumet G. Synlett 2006; 3237

For selected recent reviews on direct C–H arylation, see:

8a Ackermann L. Chem. Commun. 2010; 46: 4866
8b Fisch-Meister C, Doucet H. Green Chem. 2011; 13: 741
8c Roger J, Gottumukkala AL, Doucet H. ChemCatChem 2010; 2: 20
8d Jazzar R, Hitce J, Renaudat A, Sofack-Kreutzer J, Baudoin O. Chem. Eur. J. 2010; 16: 2654
8e Ackermann L, Vicente R, Kapdi AR. Angew. Chem. Int. Ed. 2009; 48: 9792
8f Daugulis O, Do HQ, Shabashov D. Acc. Chem. Res. 2009; 42: 1074
8g McGlacken GP, Bateman LM. Chem. Soc. Rev. 2009; 38: 2447
8h Bellina F, Rossi R. Tetrahedron 2009; 65: 10269
8i Li BJ, Yang SD, Shi ZJ. Synlett 2008; 949
8j Alberico D, Scott ME, Lautens M. Chem. Rev. 2007; 107: 174
8k Seregin IV, Gevorgyan V. Chem. Soc. Rev. 2007; 36: 1173
8l Campeau LC, Stuart DR, Fagnou K. Aldrichimica Acta 2007; 40: 35
8m Catellani M, Motti E, Della Ca’ N, Ferracioli R. Eur. J. Org. Chem. 2007; 4153
8n Satoh T, Miura M. Chem. Lett. 2007; 36: 200

9a See ref 7.
9b Fu HY, Chen L, Doucet H. J. Org. Chem. 2012; 77: 4473
9c Beladhriaa A, Beydounb K, Ammar HB, Salemc RB, Doucet H. Synthesis 2011; 2553
9d Basolo L, Beccalli EM, Borsini E, Broggini G. Tetrahedron 2009; 65: 3486
9e Basolo L, Beccalli EM, Borsini E, Broggini G, Pellegrino S. Tetrahedron 2008; 64: 8182
9f Li W, Nelson DP, Jensen MS, Hoerrner RS, Javadi GJ, Cai D, Larsen RD. Org. Lett. 2003; 5: 4835

10a Liégault B, Lapointe D, Caron L, Vlassova A, Fagnou K. J. Org. Chem. 2009; 74: 1826
10b Lafrance M, Fagnou K. J. Am. Chem. Soc. 2006; 128: 16496

11a See Ref 8e.
11b Daugulis O. Chem. Heterocycl. Compd. 2012; 48: 21
11c Ackermann L, Vicente R, Borna R. Adv. Synth. Catal. 2008; 350: 741
11d Campeau LC, Parisien M, Jean A, Fagnou K. J. Am. Chem. Soc. 2006; 128: 581

For reviews providing mechanistic discussions on palladium(0)-catalyzed direct C–H coupling, see:

12a Théveau L, Querolle O, Dupas G, Hoarau C. Tetrahedron 2013; 69: 4375
12b Verrier C, Lassalas P, Théveau L, Quéguiner G, Trécourt F, Marsais F, Hoarau C. Beilstein J. Org. Chem. 2011; 7: 1584
12c Bellina F, Rossi R. Adv. Synth. Catal. 2010; 352: 1223
12d Balcells D, Clot E, Eisenstein O. Chem. Rev. 2010; 110: 749
12e Fagnou K. Top. Curr. Chem. 2010; 292: 35
12f Bellina F, Cautericcio S, Rossi R. Curr. Org. Chem. 2008; 12: 774
12g Seregin IV, Gevorgyan V. Chem. Soc. Rev. 2007; 36: 1173

13 Pivalic acid and potassium acetate should enhance the reactivity in the case of a CMD mechanism but in our case no improvement in the conversion was observed (Table 1, entry 4). See: Lafrance M, Fagnou K. J. Am. Chem. Soc. 2006; 128: 16496
14 Iodide poisoning effect of catalyst is known to inhibit CMD reactivity. A low conversion of 10% is noted using 4-iodotoluene (Table 1, entry 16). Consequently the CMD mechanism may not be excluded. See ref. 11d.
15 General Procedure A; C-7 Direct Arylation of the Imidazo[1,2-b]pyrazoles 1–5: A microwave vial containing a stirring bar was loaded with imidazo[1,2-b]pyrazole 1–5 in 1,4-dioxane, (hetero)aryl bromide or chloride (2.0 equiv), tricyclohexylphosphine tetrafluoroborate (0.20 equiv) and cesium carbonate (2.0 equiv). The tube was evacuated and backfilled with dry argon twice. Palladium acetate (0.10 equiv) was added and the mixture was submitted to microwave irradiation with stirring at 160 °C for 4 h. It was then cooled to r.t., and 1,4-dioxane was removed under reduced pressure. The residue was purified by flash chromatography to provide the desired products 1a–5b. 2-(4-Methoxyphenyl)-1-methyl-6-phenyl-3-(4-tolyl)-7-[4-(trifluoromethyl)phenyl]-1H-imidazo[1,2-b]pyrazole (1b): The reaction was carried out as described in general procedure A using imidazo[1,2-b]pyrazole 1 (100 mg, 0.254 mmol), palladium acetate (5.7 mg, 0.0254 mmol), tricyclohexylphosphine tetrafluoroborate (18.7 mg, 0.0508 mmol), cesium carbonate (142 mg, 0.508 mmol) and 4-bromobenzotrifluoride (114 mg, 72 μL, 0.508 mmol) in 1,4-dioxane (2 mL). Standard workup followed by flash chromatography (CH₂Cl₂–petroleum ether, 1:1) yielded 1b as a pale yellow solid (123 mg, 90%); mp 226–228 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.71 (d, J = 8.1 Hz, 2 H, H_Ar), 7.58 (d, J = 8.4 Hz, 2 H, H_Ar), 7.53 (d, J = 7.9 Hz, 2 H, H_Ar), 7.47 (d, J = 8.1 Hz, 2 H, H_Ar), 7.33 (d, J = 8.5 Hz, 2 H, H_Ar), 7.25–7.29 (m, 3 H, H_Ar), 7.12 (d, J = 8.1 Hz, 2 H, H_Ar), 7.00 (d, J = 8.5 Hz, 2 H, H_Ar), 3.88 (s, 3 H, OMe), 3.30 (s, 3 H, NMe), 2.32 (s, 3 H, Me). ¹³C NMR (101 MHz, CDCl₃): δ = 160.31 (C_q), 152.26 (C_q), 140.07 (C_q), 137.17 (C_q), 136.82 (C_q), 134.27 (C_q), 132.46 (CH_Ar), 130.97 (CH_Ar), 129.19 (C_q), 129.03 (CH_Ar), 128.87 (CH_Ar), 128.18 (CH_Ar), 127.87 (² J _C–F = 33.0 Hz, C_q), 127.42 (CH_Ar), 127.14 (CH_Ar), 125.63 (C_q), 125.14 (³ J _C–F = 3.72 Hz, CH_Ar), 124.41 (¹ J _C–F = 273 Hz, C_q), 121.13 (C_q), 118.42 (C_q), 114.64 (CH_Ar), 94.33 (C_q), 55.34 (OMe), 31.73 (NMe), 21.29 (Me). IR (neat): 1603, 1322, 1118, 1066, 838, 697 cm^–1. HRMS (ESI): m/z [M + H]⁺ calcd for C₃₃H₂₇F₃N₃O: 538.21007; found: 538.21007. HRMS (ESI): m/z [M + Na]⁺ calcd for C₃₃H₂₇F₃N₃O: 560.19202; found: 560.19113. General Procedure B; One-Pot C-3 and C-7 Direct Arylation of Imidazo[1,2-b]pyrazole 6: A microwave vial containing a stirring bar was loaded with imidazo[1,2-b]pyrazole 6 in 1,4-dioxane, (hetero)aryl bromide (3.0 equiv), tricyclohexylphosphine tetrafluoroborate (0.20 equiv) and cesium carbonate (4.0 equiv). The tube was evacuated and back-filled with dry argon twice. Palladium acetate (0.10 equiv) was added and the mixture was submitted to microwave irradiation with stirring at 160 °C for 4 h. It was then cooled to r.t., and 1,4-dioxane was removed under reduced pressure. The residue was purified by flash chromatography to provide the desired products 1a, 6a and 6b. 2-(4-Methoxyphenyl)-1-methyl-6-phenyl-3,7-bis[4-(trifluoromethyl)phenyl]-1H-imidazo[1,2-b]pyrazole (6a): The reaction was carried out as described in general procedure B using imidazo[1,2-b]pyrazole 6 (100 mg, 0.329 mmol), palladium acetate (8.04 mg, 0.0329 mmol), tricyclohexylphosphine tetrafluoroborate (24.0 mg, 0.0658 mmol), caesium carbonate (369 mg, 1.32 mmol) and 4-bromobenzotrifluoride (222 mg, 138 μL, 0.987 mmol) in 1,4-dioxane (2 mL). Standard workup followed by flash chromatography (CH₂Cl₂–petroleum ether, 3:7) yielded 6a as a white solid (151 mg, 78%); mp 220–222 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.01 (d, J = 8.4 Hz, 2 H, H_Ar), 7.47–7.64 (m, 8 H, H_Ar), 7.29–7.41 (m, 5 H, H_Ar), 7.07 (d, J = 8.4 Hz, 2 H, H_Ar), 3.92 (s, 3 H, OMe), 3.33 (s, 3 H, NCH₃). ¹³C NMR (101 MHz, CDCl₃): δ = 160.76 (C_q), 152.49 (C_q), 140.08 (C_q), 136.81 (C_q), 133.96 (C_q), 132.34 (CH_Ar), 132.28 (C_q), 131.09 (C_q), 131.05 (CH_Ar), 128.78 (CH_Ar), 128.37 (² J _C–F = 32.6 Hz, C_q), 128.27 (CH_Ar), 128.20 (² J _C–F = 32.8 Hz, C_q), 127.64 (CH_Ar), 126.73 (CH_Ar), 125.25 (³ J _C–F = 3.70 Hz, 2 × CH_Ar), 124.36 (¹ J _C–F = 273 Hz, C_q), 124.18 (¹ J _C–F = 273 Hz, C_q), 120.39 (C_q), 117.03 (C_q), 114.99 (CH_Ar), 94.65 (C_q), 55.39 (OMe), 31.74 (NMe). IR (neat): 1613, 1320, 1249, 1162, 1103, 1076, 1064, 1016, 834 cm^–1. HRMS (ESI): m/z [M + H] calcd for C₃₃H₂₄F₆N₃O: 592.18181; found: 592.18163.

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