Synlett 2016; 27(07): 1073-1076
DOI: 10.1055/s-0035-1561265
letter
© Georg Thieme Verlag Stuttgart · New York

Regioselective Suzuki–Miyaura Reactions of the Bis(triflate) of 6,7-Dihydroxy-2,2-dimethylchroman-4-one

Dávid Pajtás
a   Department of Organic Chemistry, University of Debrecen, 4032 Debrecen, Egyetem tér 1, Hungary
b   Department of Chemistry, University of Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
,
Károly Dihen
a   Department of Organic Chemistry, University of Debrecen, 4032 Debrecen, Egyetem tér 1, Hungary
b   Department of Chemistry, University of Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
,
Krisztina Kónya
a   Department of Organic Chemistry, University of Debrecen, 4032 Debrecen, Egyetem tér 1, Hungary
b   Department of Chemistry, University of Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
,
Peter Langer*
b   Department of Chemistry, University of Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany   Email: peter.langer@uni-rostock.de
c   Leibniz-Institute for Catalysis e.V. at the University of Rostock (LIKAT), Albert-Einstein-Str. 3a, 18059 Rostock, Germany
› Author Affiliations
Further Information

Publication History

Received: 03 November 2015

Accepted after revision: 06 December 2015

Publication Date:
21 January 2016 (online)


Dedicated in memory to our dear colleague and friend Professor Tamás Patonay, PhD, DSc

Abstract

6,7-Diarylchromanone derivatives were prepared by Suzuki–Miyaura reactions of the bis(triflate) of 6,7-dihydroxy-2,2-dimethylchroman-4-one. Due to electronic factors the first attack proceeded with very good site selectivity at position 7.

 
  • References and Notes

  • 1 Lemos LM. S, Martins TB, Tanajura GH, Gazoni VF, Bonaldo J, Strada CL, Silva MG, Dall’Oglio EL, Sousa JP. T, Martins DT. O. J. Ethnopharmacol. 2012; 141: 432
  • 2 Nascimento AM, Oliveira DC. R. Helv. Chim. Acta 2014; 97: 146
  • 3 Wanga H, Sun Q.-Y, Yang F.-M, Long C.-L, Wang Y.-H, Tang G.-H, Zhao F.-W, Niua H.-M, Huang Q.-Q, Xu J.-J, Wataya Y, Ma L.-J. Helv. Chim. Acta 2010; 93: 2183
  • 4 Tanaka Y, Honma D, Tamura M, Yanagida A, Zhao P, Shoji T, Tagashira M, Shibusawa Y, Kanda T. Phytochem. Lett. 2012; 5: 514
  • 5 Albrecht U, Lalk M, Langer P. Bioorg. Med. Chem. 2005; 13: 1531
  • 6 Cottiglia F, Dhanapal B, Sticher O, Heilmann J. J. Nat. Prod. 2004; 67: 537
  • 7 Hoettecke N, Rotzoll S, Albrecht U, Lalk M, Fischer C, Langer P. Bioorg. Med. Chem. 2008; 16: 10319
  • 8 Park JH, Lee SU, Kim SH, Shin SY, Lee JY, Shin C.-G, Yoo KH, Lee YS. Arch. Pharm. Res. 2008; 31: 1
  • 9 Gamal-Eldeena AM, Abdel-Lateff A, Okinoc T. Environ. Toxicol. Pharmacol. 2009; 28: 317
  • 10 Zhao P.-L, Li J, Yang G.-F. Bioorg. Med. Chem. 2007; 15: 1888
  • 11 Nicolaou KC, Pfefferkorn JA, Roecker AJ, Cao G.-G, Barluenga S, Mitchell HJ. J. Am. Chem. Soc. 2000; 122: 9939
  • 12 Nicolaou KC, Pfefferkorn JA, Cao G.-G. Angew. Chem. Int. Ed. 2000; 39: 739
  • 13 Tímár T, Lévai A, Eszenyi T, Sebők P. J. Heterocycl. Chem. 2000; 37: 1389
  • 14 Lévai A, Tímár T, Sebők P, Eszenyi T. Heterocycles 2000; 53: 1193
  • 15 Dubrovskiy AV, Larock RC. Tetrahedron 2013; 69: 2789
  • 16 López CS, Erra-Balsells R, Bonesi SM. Tetrahedron Lett. 2010; 51: 4387
  • 17 Iguchi D, Erra-Balsells R, Bonesi SM. Tetrahedron Lett. 2014; 55: 4653
  • 18 Dubrovskiy AV, Larock RC. Org. Lett. 2010; 12: 3117
  • 19 Miyaura N, Yamada K, Suzuki A. Tetrahedron Lett. 1979; 36: 3437
  • 20 Miyaura N, Suzuki A. Chem. Commun. 1979; 866
  • 21 Suzuki A. Pure Appl. Chem. 1985; 57: 1749
  • 22 Negishi E.-i. Handbook of Organopalladium for Organic Synthesis . Vol. 1 and 2. Wiley-Interscience; New York: 2002
  • 23 Beller M, Bolm C. Transition Metals for Organic Synthesis: Building Blocks and Fine Chemicals . Wiley-VCH; Weinheim: 2004. 2nd ed., Vol. 1 and 2
  • 24 de Meijere A, Diederich F. Metal-Catalyzed Cross-Coupling Reactions . Wiley-VCH; Weinheim: 2004. 2nd ed., Vol. 1 and 2
  • 25 King AO, Yasuda N. Organometallics in Process Chemistry . Larsen RD. Springer; Berlin: 2004
  • 26 Ackermann L. Modern Arylation Methods . Wiley-VCH; Weinheim: 2009
  • 27 Tsuji J. Palladium Reagents and Catalysts . 2nd ed. Wiley; Chichester: 2004
  • 28 Suzuki A. Modern Arene Chemistry . Astruc D. Wiley-VCH; Weinheim: 2002
  • 29 Suzuki A. J. Organomet. Chem. 2002; 653: 54
  • 30 Hassan J, Sévignon M, Gozzi C, Schulz E, Lemaire M. Chem. Rev. 2002; 102: 1359
  • 31 Wu XF, Anberasan P, Neumann H, Beller M. Angew. Chem. Int. Ed. 2010; 49: 9047
  • 32 Corbet J.-P, Mignani G. Chem. Rev. 2006; 106: 2651
  • 33 Miyaura N. Top. Curr. Chem. 2002; 219: 11
  • 34 Roglans A, Pla-Quintana A, Moreno-Mañas M. Chem. Rev. 2006; 106: 4622
  • 35 Yin L, Liebscher J. Chem. Rev. 2007; 107: 133
  • 36 Wolfe JP, Tomori H, Sadighi JP, Yin J, Buchwald SL. J. Org. Chem. 2000; 65: 1158
  • 37 Nishiyama M, Yamamoto T, Koie Y. Tetrahedron Lett. 1998; 39: 617
  • 38 Zapf A, Jackstell R, Rataboul F, Riermeier T, Monsees A, Fuhrmann C, Shaikh N, Dingerdissen U, Beller M. Chem. Commun. 2004; 38
  • 39 Rataboul F, Zapf A, Jackstell R, Harkal S, Riermeier T, Monsees A, Dingerdissen U, Beller M. Chem. Eur. J. 2004; 10: 2983
  • 40 Littke AF, Dai CY, Fu GC. J. Am. Chem. Soc. 2000; 122: 4020
  • 41 Hassan Z, Hussain M, Villinger A, Langer P. Tetrahedron 2012; 68: 6305
  • 42 Espino G, Kurbangalieva A, Brown JM. Chem. Commun. 2007; 1742
  • 43 Kamikawa T, Hayashi T. Tetrahedron Lett. 1997; 38: 7087
  • 44 Roy AH, Hartwig JF. Organometallics 2004; 23: 194
  • 45 Hassan Z, Hussain M, Langer P. Synlett 2011; 1827
  • 46 Schnürch M, Flasik R, Khan AF, Spina M, Mihovilovic MD, Stanetty P. Eur. J. Org. Chem. 2006; 3283
  • 47 Wang R, Manabe K. Synthesis 2009; 1405
  • 48 Handy ST, Zhang Y. Chem. Commun. 2006; 299
  • 49 Zahid H, Patonay T, Langer P. Synlett 2013; 24: 412
  • 50 Malik I, Hussain M, Hung NT, Villinger A, Langer P. Synlett 2010; 2244
  • 51 Eleya N, Malik I, Reimann S, Wittler K, Hein M, Patonay T, Villinger A, Ludwig R, Langer P. Eur. J. Org. Chem. 2012; 1639
  • 52 Tímár T, Jászberényi JC. J. Heterocycl. Chem. 1988; 25: 871
  • 53 Procedure for Synthesizing 6,7-Diaryl-2,2-dimethylchroman-4-one Derivatives To a mixture of 2,2-dimethyl-6,7-ditriflyloxychroman-4-one (150 mg, 0.318 mmol), K3PO4 (202 mg, 0,95 mmol), and boronic acid (0.70 mmol) in dry 1,4-dioxane (4 mL) was added Pd(PPh3)4 (22 mg, 0.019 mmol) in a dried pressure tube under argon. The reaction mixture was stirred and heated in an aluminium heating block. The solvent was evaporated in vacuum, and the solid mixture was submitted to adsorptive filtration on silica gel using acetone as eluent removing the inorganic compounds. Silica was added to the solution, the acetone was evaporated, and the mixture was purified by column chromatography (eluent: heptane–EtOAc, the ratio is given below) giving the diarylated product. 6,7-Bis(4-methoxyphenyl)-2,2-dimethylchroman-4-oneStarting with 4 (150 mg, 0.32 mmol), K3PO4 (202 mg, 0.95 mmol), Pd(PPh3)4 (22 mg, 6 mol%), (4-methoxyphenyl)boronic acid (5b, 106 mg, 0.70 mmol), and 1,4-dioxane (4 mL), 6b was isolated as a white solid (84 mg 68%), mp 150–152.5 °C. 1H NMR (300 MHz, 298 K, CDCl3): δ = 7.61 (s, 1 H, 5-H), 7.05 (d, J= 10.5 Hz, 2 H, 2′,6′′-H) 6.98 (d, J= 10.5 Hz, 2 H, 2′,6′-H), 6.93 (s, 1 H, 8-H), 6.81 (m, 4 H, 3′,5′-H, 3′′,5′′-H), 3.72 (s, 3 H, 4′′-OCH3), 3.71 (s, 3 H, 4′-OCH3), 2.83 (s, 2 H, 3-H), 1.44 (s, 6 H, 2-CH3). 13C NMR (75 MHz, 298 K, CDCl3): δ = 191.7.7 (C-4), 158.6 (C-8a), 158.3 (C-4′′), 157.9 (C-4′), 147.5 (C-7), 132.5 (C-1′′), 132.3 (C-1′), 132.0 (C-6), 130.4 (C-2′,6′, C-2′′,6′′), 127.4 (C-5), 119.3 (C-8), 118.5 (C-4a), 113.6 (C-3′,5′, C-3′′5′′), 79.6 (C-2), 55.0 (OCH3), 48.0 (C-3), 26.2 (CH3). IR (ATR): υ = 2994, 2954, 2835, 1683, 1606, 1512, 1466, 1430, 1403, 1296, 1243, 1167, 1109, 1025, 951, 831, 655, 564, 549 cm–1. GC–MS (EI, 70 eV): m/z = 388 [M+∙, 100%], 373, 333, 261, 189. HRMS: m/z calcd for C25H24O4: 388.16691; found: 388.16649.
  • 54 Procedure for Synthesizing 7-Aryl-2,2-dimethyl-6-triflyloxy-chroman-4-one Derivatives To a mixture of 2,2-dimethyl-6,7-ditriflyloxychroman-4-one (150 mg, 0.318 mmol), K3PO4 (135 mg, 0,64 mmol), and boronic acid (0.349 mmol) in dry 1,4-dioxane (4 mL) was added Pd(PPh3)4 (11 mg, 0.0095 mmol) in a dried pressure tube under argon. The reaction mixture was stirred and heated in an aluminium heating block. The solvent was evaporated in vacuum, then the solid mixture was submitted to adsorptive filtration on silica gel using acetone as eluent removing the inorganic compounds. Silica was added to the solution, the acetone was evaporated, and the mixture was purified by column chromatography (eluent: heptane–EtOAc mixture, the ratio is given below) giving the monosubsituted product. 7-(4-Methoxyphenyl)-2,2-dimethyl-6-(triflyloxy)chroman-4-oneStarting with 4 (150 mg, 0.32 mmol), K3PO4 (135 mg, 0.64 mmol), Pd(PPh3)4 (11 mg, 3 mol%), (4-methoxyphenyl)boronic acid (5b, 53 mg, 0.35 mmol), and 1,4-dioxane (4 mL), 7b was isolated as a yellow oil (93 mg 68%), eluent: toluene–heptane (6:1). 1H NMR (300 MHz, 298 K, DMSO-d 6): δ = 7.71 (s, 1 H, 5-H), 7.47 (d, 2 H, J= 8.7 Hz, 2′,6′-H), 7.06 (d, 2 H, J= 8.7 Hz, 3′,5′-H), 3.82 (s, 3 H, OCH3), 2.92(s, 2 H, 3-H), 1.44 (s, 6 H, CH3). 13C NMR (75 MHz, 298 K, DMSO-d 6): δ = 190.7 (C-4), 160.0 (C-4′), 158.6 (C-8a), 142.1 (C-6), 140.1 (C-7), 130.5 (C-2′,6′), 126.1 (C-1′), 120.9 (C-5), 118.9 (C-8), 118.8 (C-4a), 114.2 (C-3′,5′), 80.6 (C-2), 55.3 (OCH3), 47.3 (C-3), 26.0 (CH3). IR (ATR): υ = 2978, 2839, 1696, 1607, 1518, 1423, 1205, 1136, 1097, 1030, 915, 890, 832, 613, 564, 513 cm–1. GC–MS (EI, 70 eV): m/z = 430 [M+∙], 297, 255, 241 (100%), 215, 185, 157, 83. HRMS: m/z calcd for C19H17F3O6S: 430.06979; found: 430.06967.
  • 55 Procedure for Synthesizing Differently Substituted 6,7-Diaryl-2,2-dimethylchroman-4-one DerivativesTo a mixture of 7-aryl-2,2-dimethyl-6-triflyloxychroman-4-one (0.120 mmol), K3PO4 (76 mg, 0,360 mmol), and boronic acid (0.264 mmol) in dry 1,4-dioxane (4 mL) was added Pd(PPh3)4 (8.3 mg, 0.0072 mmol) in a dried pressure tube under argon. The reaction mixture was stirred and heated in an aluminium heating block. The solvent was evaporated in vacuum, and then the solid mixture was submitted to adsorptive filtration on silica gel using acetone as eluent removing the inorganic compounds. Silica was added to the solution, the acetone was evaporated, and the mixture was purified by column chromatography (eluent: heptane–EtOAc mixture, the ratio is given below) giving the differently substituted product.6-(4-Hydroxyphenyl)-7-(4-methoxyphenyl)-2,2-dimethylchroman-4-oneStarting with 7b (50 mg, 0.12 mmol), K3PO4 (76 mg, 0.36 mmol), Pd(PPh3)4 (8.1 mg, 6 mol%), (4-hydroxyphenyl)boronic acid (5e, 35 mg, 0.264 mmol), and 1,4-dioxane (4 mL), 8g was isolated as a light yellow solid (36 mg 83%), mp 182.5–185°C, eluent: heptane–EtOAc (2:1). 1H NMR(300 MHz, 298 K, CDCl3): δ = 9.37 (s, 1 H, 5-H), 7.59 (s, 1 H, 8-H), 7.06 (d, J= 8.7 Hz, 2 H, 2′′,6′′-H), 6.86 (d, J= 8.7 Hz, 2 H, 2′,6′-H), 6.82 (d, J= 8.7 Hz, 2 H, 3′′,5′′-H), 6.62 (d, J= 8.7 Hz, 2 H, 3′,5′-H), 6.55 (s, 1 H, OH), 3.73 (s, 3 H, OCH3), 2.82 (s, 2 H, 3-H), 1.44 (s, 6 H, CH3). 13C NMR (75 MHz, 298 K, CDCl3): δ = 191.7 (C-4), 158.6 (C-8a), 158.1 (C-4′′), 156.1 (C-4′), 147.5 (C-7), 132.9 (C-1′′), 132.1 (C-1′), 130.6 (C-6), 130.4 (C-2′,6′, C-2′′,6′′), 127.2 (C-5), 119.2 (C-8), 118.4 (C-4a), 115.0 (C-3′,5′), 113.5 (C-3′′,5′′), 79.6 (C-2), 55.0 (OCH3), 48.0 (C-3), 26.2 (CH3). IR (ATR): υ = 3299, 2921, 2847, 1737, 1668, 1602, 1512, 1406, 1243, 1163, 1109, 1026, 950, 834, 654, 560 cm–1. GC–MS (EI, 70 eV): m/z = 374 [M+∙, 100%], 359, 319, 290, 247, 219, 202, 179, 152. HRMS: m/z calcd for C24H22O4: 374.15126; found: 374.15110.