Ruthenium-Catalyzed Oxidative C–H Bond Alkenylation of 2-Phenylimidazo[1,2-a]pyridine

Abstract

Monoalkenylation of sp² C–H bonds directed by the innate reactivity of imidazo[1,2-a]pyridine to afford 2-(2′-alkenylphenyl)imidazo[1,2-a]pyridine with high levels of diastereoselectivity is described. The methodology is employed to generate di-substituted alkenes by using a cationic ruthenium(II) catalyst in the presence of AgSbF₆ and Cu(OAc)₂·H₂O under air.

Key words

C–H activation - Diastereoselectivity - regioselectivity - ruthenium - alkenylation

• References and Notes


For selected reviews for C–H activation, see:
• 1a Engle KM, Mei T.-S, Wasa M, Yu J.-Q. Acc. Chem. Res. 2012; 45: 788
• 1b Yamaguchi J, Yamaguchi AD, Itami K. Angew. Chem. Int. Ed. 2012; 51: 8960
• 1c Ackermann L. Chem. Rev. 2011; 111: 1315
• 1d McMurray L, Ohara F, Gaunt MJ. Chem. Soc. Rev. 2011; 40: 1885
• 1e Trost BM. Science 1991; 254: 1471
• 1f Trost BM. Acc. Chem. Res. 2002; 35: 695
• 2a Sarkar SD, Liu W, Kozhushkov SI, Ackermann L. Adv. Synth. Catal. 2014; 356: 1461
• 2b Gandeepan P, Parthasarathy K, Cheng C.-H. J. Am. Chem. Soc. 2010; 132: 8569
• 2c Lyons TW, Sanford MS. Chem. Rev. 2010; 110: 1147 ; and references therein
• 2d Chen X, Engle KM, Wang D.-H, Yu J.-Q. Angew. Chem. Int. Ed. 2009; 48: 5094
• 2e Ackermann L, Vicente R, Kapdi AR. Angew. Chem. Int. Ed. 2009; 48: 9792
• 2f Daugulis O, Do H.-Q, Shabashov D. Acc. Chem. Res. 2009; 42: 1074
• 2g Alberico D, Scott ME, Lautens M. Chem. Rev. 2007; 107: 174
• 2h Stuart DR, Fagnou K. Science 2007; 316: 1172
• 2i Dick AR, Sanford MS. Tetrahedron 2006; 62: 2439
• 3a Lewis JC, Bergman RG, Ellman JA. Acc. Chem. Res. 2008; 41: 1013
• 3b Daugulis O, Zaitsev VG, Shabashov D, Pham Q.-N, Lazareva A. Synlett 2006; 3382
• 3c Miura M, Nomura M. Top. Curr. Chem. 2002; 219: 212
• 3d Dyker G. Angew. Chem. Int. Ed. 1999; 38: 1698
• 4a Arockiam PB, Fischmeister C, Bruneau C, Dixneuf PH. Green Chem. 2011; 13: 3075
• 4b Hashimoto Y, Ueyama T, Fukutani T, Hirano K, Satoh T, Miura M. Chem. Lett. 2011; 40: 1165
• 5a Hashimoto Y, Ortloff T, Hirano K, Satoh T, Bolm C, Miura M. Chem. Lett. 2012; 41: 151
• 5b Li B, Devaraj K, Darcel C, Dixneuf P. Green Chem. 2012; 14: 2706
• 6 Oi S, Fukita S, Hirata N, Watanuki N, Miyano S, Inoue Y. Org. Lett. 2001; 3: 2579
• 7a Colby DA, Bergman RG, Ellman JA. Chem. Rev. 2010; 110: 624
• 7b Park YJ, Jun C.-H. Bull. Korean Chem. Soc. 2005; 26: 871
• 7c Jun C.-H, Moon CW, Lee D.-Y. Chem. Eur. J. 2002; 8: 2422

For reviews on catalytic C–H bond activation with a Ru catalyst, see:
• 8a Kozhushkov SI, Ackermann L. Chem. Sci. 2013; 4: 886 ; and references therein
• 8b Arockiam PB, Bruneau C, Dixneuf PH. Chem. Rev. 2012; 112: 5879 ; and references therein
• 8c Ackermann L. Chem. Rev. 2011; 111: 1315
• 8d Ackermann L, Vicente R. Top. Curr. Chem. 2010; 292: 211
• 8e Ackermann L. Chem. Commun. 2010; 46: 4866
• 8f Ackermann L, Vicente R, Kapdi AR. Angew. Chem. Int. Ed. 2009; 48: 9792
• 8g Ritleng V, Sirlin C, Pfeffer M. Chem. Rev. 2002; 102: 1731
• 9 Fujiwara Y, Moritani I, Matsuda M, Teranishi S. Tetrahedron Lett. 1968; 3863
• 10 Lewis LN, Smith JF. J. Am. Chem. Soc. 1986; 108: 2728
• 11 Murai S, Kakiuchi F, Sekine S, Tanaka Y, Kamatani A, Sonoda M, Chatani N. Nature 1993; 366: 529
• 12 Lim Y.-G, Kim YH, Kang J.-B. J. Chem. Soc., Chem. Commun. 1994; 2267
• 13a Ackermann L, Althammer A. Angew. Chem. Int. Ed. 2006; 45: 2619
• 13b Ackermann L. Org. Lett. 2005; 7: 3123
• 13c Ackermann L, Lygin AV, Hofmann N. Angew. Chem. Int. Ed. 2011; 50: 6379

For selected examples of Ru-catalyzed C–H activation, see:
• 14a Li H, Xie X, Wang L. Chem. Commun. 2014; 50: 4218
• 14b Zhao P, Niu R, Wang F, Han K, Li X. Org. Lett. 2012; 14: 4166
• 14c Graczyk K, Ma W, Ackermann L. Org. Lett. 2012; 14: 4110
• 14d Padala K, Pimparkar S, Madasamy P, Jeganmohan M. Chem. Commun. 2012; 48: 7140
• 14e Arockiam PB, Fischmeister C, Bruneau C, Dixneuf PH. Angew. Chem. Int. Ed. 2010; 49: 6629
• 14f Arockiam PB, Fischmeister C, Bruneau C, Dixneuf PH. Green Chem. 2011; 13: 3075
• 14g Ackermann L, Hofmann N, Vicente R. Org. Lett. 2011; 13: 1875
• 14h Ackermann L. Org. Lett. 2005; 7: 3123
• 15 Babu PA, Narasu ML, Srinivas K. ARKIVOC 2007; (ii): 247
• 16a Kaminsky JJ, Doweyko AM. J. Med. Chem. 1997; 40: 427
• 16b Kaesura Y, Nishino S, Inoue Y, Tomoi M, Taksugi H. Chem. Pharm. Bull. 1992; 40: 371
• 16c Starrett JE. Jr, Montzka TA, Crosswell AR, Cavanagh RL. J. Med. Chem. 1989; 32: 2204
• 16d Kaminsky JJ, Puchalski C, Solomon DM, Rizvi RK, Conn DJ, Elliot AJ, Lovey RG, Guzik H, Chui PJ. S, Long JF, McPhail AT. J. Med. Chem. 1989; 32: 1686
• 17a Cheng Y, Moraski GC, Cramer J, Miller MJ, Schorey JS. PLOS One 2014; 9: e87483
• 17b Rewankar GR, Matthews JR, Robins RK. J. Med. Chem. 1975; 18: 1253
• 17c Rival Y, Grassy G, Michel G. Chem. Pharm. Bull. 1992; 40: 1170
• 18 Marhadour S, Marchand P, Pagniez F, Bazin MA, Picot C, Lozach O, Ruchaud S, Antoine M, Meijer L, Rachidi N, Le Pape P. Eur. J. Med. Chem. 2012; 58: 543
• 19 Abrahams KA, Cox JA, Spivey VL, Loman NJ, Pallen MJ, Constantinidou C, Fernández R, Alemparte C, Remuiñán MJ, Barros D, Ballell L, Besra GS. PLOS One 2012; 7: e52951
• 20a Puerstinger G, Paeshuyse J, Declercq E, Neyts J. Bioorg. Med. Chem. Lett. 2007; 17: 390
• 20b Gudmundsson KS, Williams JD, Drach JC, Townsend LB. J. Med. Chem. 2003; 46: 1449
• 20c Hamdouchi C, de Blas J, del Prado M, Gruber J, Heinz BA, Vance L. J. Med. Chem. 1999; 42: 50
• 20d Pan S, Wang G, Shinazi RF, Zhao K. Tetrahedron Lett. 1998; 39: 8191
• 20e Gudmundsson KS, Drach JC, Townsend LB. J. Org. Chem. 1997; 62: 3453
• 20f Gueiffier A, Lhassani M, Elhakmoui A, Snoeck R, Andrei G, Chavignion O, Teulade JC, Kerbal A, Essassi M, Debouzy JC, Witurowo JP, Blache Y, Balzarini J, De Clercq E, Chapat JP. J. Med. Chem. 1996; 39: 2856
• 20g Elhakmoui A, Gueiffier A, Milhavet JC, Blache Y, Chapat JP. Bioorg. Med. Chem. Lett. 1994; 4: 1937
• 21a Fisher MH, Lusi A. J. Med. Chem. 1972; 15: 982
• 21b Rival Y, Grassy G, Taudou A, Ecalle R. Eur. J. Med. Chem. 1991; 26: 13
• 22a Biftu T, Feng D, Fisher M, Liang GB, Qian X, Scribner A, Dennis R, Lee S, Liberator PA, Brown C, Gurnett A, Leavitt PS, Thompson D, Mathew J, Misura A, Samaras S, Tamas T, Sina JF, McNulty KA, McKnight CG. Bioorg. Med. Chem. Lett. 2006; 16: 2479
• 22b Ismail MA, Arafa RK, Wenzler T, Brun R, Tanious FA, Wilson WD, Boykin DW. Bioorg. Med. Chem. 2008; 16: 683
• 23a Gudmundsson KS, Johns BA. Bioorg. Med. Chem. Lett. 2007; 17: 2735
• 23b Gudmundsson KS, Johns BA. Org. Lett. 2003; 5: 1369
• 24 Rupert KC, Henry JR, Dodd JH, Wadsworth SA, Cavender DE, Olini GC, Fahmy B, Siekierka JJ. Bioorg. Med. Chem. Lett. 2003; 13: 347
• 25 Langer SZ, Arbilla S, Benavides J, Scatton B. Adv. Biochem. Psychopharmacol. 1990; 46: 61

For synthetic routes to the imidazo[1,2-a]pyrimidine ring, see:
• 26a Nair DK, Mobin SM, Namboothiri IN. N. Org. Lett. 2012; 14: 4580
• 26b Chemyak N, Gevorgyan V. Angew. Chem. Int. Ed. 2010; 49: 2743
• 26c Tolmachova NA, Gerus II, Vdovenko SI, Haufe G, Kirzhner YA. Synthesis 2007; 3797
• 26d Gerencser J, Panka G, Nagy T, Egyed O, Dorman G, Uerge L, Darvas F. J. Comb. Chem. 2005; 7: 530
• 27a Ackermann L. Acc. Chem. Res. 2014; 47: 281
• 27b Padala K, Jeganmohan M. Org. Lett. 2012; 14: 1134
• 27c Ackermann L, Pospech J. Org. Lett. 2011; 13: 4153
• 27d Ackermann L, Wang L, Wolfram R, Lygin AV. Org. Lett. 2012; 14: 728
• 27e Padala K, Jeganmohan M. Org. Lett. 2011; 13: 6144
• 28a Cao H, Zhan H, Lin Y, Lin X, Du Z, Jiang H. Org. Lett. 2012; 14: 1688
• 28b Koubachi J, Berteina-Raboin S, Mouaddib A, Guillaumet G. Synthesis 2009; 271
• 29 Lanke V, Prabhu KR. Org. Lett. 2013; 15: 2818
• 30a Sharma A, Singh M, Rai NN, Sawant D. Beilstein J. Org. Chem. 2013; 9: 1235
• 30b Agarwal PK, Sharma SK, Sawant D, Kundu B. Tetrahedron 2009; 65: 1153
• 31a Mehta VP, García-López JA, Greaney MF. Angew. Chem. Int. Ed. 2014; 53: 1529
• 31b Suzuki C, Morimoto K, Hirano K, Satoh T, Miura M. Adv. Synth. Catal. 2014; 356: 1521
• 31c Lanke V, Prabhu KR. Org. Lett. 2013; 15: 6262
• 31d Zhang L.-Q, Yang S, Huang X, You J, Song F. Chem. Commun. 2013; 49: 8830
• 32 Typical Procedure: A mixture of 5a (100 mg, 0.515 mmol), ruthenium p-cymene dichloride dimer (10 mol%, 0.052 mmol), silver hexafluoroantimonate (20 mol%, 0.103 mmol) and copper acetate monohydrate (0.515 mmol) in dichloroethane (2 mL) was stirred at r.t. for 1 min, then acrylate (0.773 mmol) was added. The mixture was heated to 100 °C in an open air atmosphere for 24 h. On completion of the reaction (monitored by TLC), the mixture was cooled to r.t., diluted with EtOAc, passed through a short Celite bed, and washed repeatedly with pure EtOAc. The combined organic layer was concentrated under reduced pressure. The crude product was purified on a silica gel column (EtOAc–hexane, 1:4) to give 8a as an off-white solid; mp 95 °C. IR (KBr): 3035, 2971, 1729, 1634, 1321, 1173 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.23 (d, J = 15.9 Hz, 1 H), 8.16 (d, J = 6.7 Hz, 1 H), 7.91 (d, J = 7.6 Hz, 1 H), 7.66 (d, J = 7.7 Hz, 2 H), 7.62 (s, 1 H), 7.48 (t, J = 7.4 Hz, 1 H), 7.39 (t, J = 7.4 Hz, 1 H), 7.21 (t, J = 6.9 Hz, 1 H), 6.81 (t, J = 6.7 Hz, 1 H), 6.45 (d, J = 15.8 Hz, 1 H), 3.79 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 167.6, 145.4, 144.6, 143.9, 134.5, 133.1, 130.3, 130.1, 128.2, 127.2, 125.8, 125.1, 119.4, 117.8, 112.7, 112.1, 51.8. MS (ES+): m/z = 279.1 [M + 1]⁺ .
• 33 Flegeau EF, Bruneau C, Dizneuf PH, Jutand A. J. Am. Chem. Soc. 2011; 133: 10161
• 34 Kommagalla Y, Mullapudi VB, Francis F, Ramana CV. Catal. Sci. Technol. 2015; 5: 114