A Domino Palladium Catalysis: Synthesis of 7-Methyl-5H-dibenzo[a,c][7] annulen-5-ones

This paper is affectionately dedicated to Professor Kavirayani R. Prasad, Department of Organic Chemistry, Indian Institute of Science, Bangalore, India

Abstract

A domino Pd-catalyzed reaction of 1-(2-bromophenyl)ethanones for the synthesis of novel 7-methyl-5H-dibenzo[a,c][7]annulen-5-ones, a carbon core structure present in colchicinoid natural products, is presented. The reaction is proposed to proceed via intermolecular homobiaryl coupling and intramolecular aldol condensation.

Key words

Pd catalysis - homobiaryl coupling - domino reaction - aldol condensation - 2-bromoacetophenones

• References and Notes

• 1 Tietze LF. Chem. Rev. 1996; 96: 115

For reviews on C–H activations, see:
• 2a Shibasaki M, Vogl EM, Ohshima T. Adv. Synth. Catal. 2004; 346: 1533
• 2b Alberico D, Scott ME, Lautens M. Chem. Rev. 2007; 107: 174
• 2c D’Souza DM, Müller TJ. J. Chem. Soc. Rev. 2007; 36: 1095
• 2d Minatti A, Muñiz K. Chem. Soc. Rev. 2007; 36: 1142
• 2e Catellani M, Motti E, Della Ca’ N. Acc. Chem. Res. 2008; 41: 1512
• 2f Daugulis O, Do H.-Q, Shabashov D. Acc. Chem. Res. 2009; 42: 1074
• 2g Chen X, Engle KM, Wang D.-H, Yu J.-Q. Angew. Chem. Int. Ed. 2009; 48: 5094 ; Angew. Chem. 2009, 121, 5196
• 2h Muñiz K. Angew. Chem. Int. Ed. 2009; 48: 9412 ; Angew. Chem. 2009, 121, 9576
• 2i Xu L.-M, Li B.-J, Yang Z, Shi Z.-J. Chem. Soc. Rev. 2010; 39: 712
• 2j Sehnal P, Taylor RJ. K, Fairlamb IJ. S. Chem. Rev. 2010; 110: 824
• 2k Lyons TW, Sanford MS. Chem. Rev. 2010; 110: 1147
• 2l Bras JL, Muzart J. Chem. Rev. 2011; 111: 1170
• 2m Ackermann L. Chem. Rev. 2011; 111: 1315

For recent Pd-catalyzed domino transformations, see:
• 3a Thirunavukkarasu VS, Parthasarathy K, Cheng C.-H. Angew. Chem. Int. Ed. 2008; 47: 9462 ; Angew. Chem. 2008, 120, 9604
• 3b Cvengroš J, Schütte J, Schlörer N, Neudörfl J, Schmalz H.-G. Angew. Chem. Int. Ed. 2009; 48: 6148 ; Angew. Chem. 2009, 121, 6264
• 3c Hu Y, Yu C, Ren D, Hu Q, Zhang L, Cheng D. Angew. Chem. Int. Ed. 2009; 48: 5448 ; Angew. Chem. 2009, 121, 5556
• 3d Levi ZU, Tilley TD. J. Am. Chem. Soc. 2009; 131: 2796
• 3e Tietze LF, Düfert A, Lotz F, Sölter L, Oum K, Lenzer T, Beck T, Herbst-Irmer R. J. Am. Chem. Soc. 2009; 131: 17879
• 3f Tietze LF, Redert T, Bell HP, Hellkamp S, Levy LM. Chem. Eur. J. 2008; 14: 2527
• 3g Tietze LF, Düfert MA, Hungerland T, Oum K, Lenzer T. Chem. Eur. J. 2011; 17: 8452
• 3h Satyanarayana G, Maichle-Mössmer C, Maier ME. Chem. Commun. 2009; 1571
• 3i Wang S, Xie K, Tan Z, An X, Zhou X, Guo C.-C, Peng Z. Chem. Commun. 2009; 6469
• 3j Li R.-J, Pi S.-F, Liang Y, Wang Z.-Q, Song R.-J, Chen G.-X, Li J.-H. Chem. Commun. 2010; 46: 8183
• 3k Chen X, Wang H, Jin X, Feng J, Wang Y, Lu P. Chem. Commun. 2011; 47: 2628
• 3l Bryan CS, Lautens M. Org. Lett. 2008; 10: 4633
• 3m Jana R, Chatterjee I, Samanta S, Ray JK. Org. Lett. 2008; 10: 4795
• 3n Luo Y, Pan X, Wu J. Org. Lett. 2011; 13: 1150
• 3o Motti E, Della Ca’ N, Xu D, Piersimoni A, Bedogni E, Zhou Z.-M, Catellani M. Org. Lett. 2012; 14: 5792
• 3p Piou T, Neuville L, Zhu J. Angew. Chem. Int. Ed. 2012; 51: 11561 ; Angew. Chem. 2012, 124, 11729
• 3q Hashmi AS. K, Ghanbari M, Rudolph M, Rominger F. Chem. Eur. J. 2012; 18: 8113
• 3r Hashmi AS. K, Lothschütz C, Döpp R, Ackermann M, Becker JD. B, Rudolph M, Scholz C, Rominger F. Adv. Synth. Catal. 2012; 354: 133
• 3s Hashmi AS. K, Lothschütz C, Döpp R, Rudolph M, Ramamurthi TD, Rominger F. Angew. Chem. Int. Ed. 2009; 48: 8243 ; Angew. Chem. 2009, 121, 8392
• 4 For a review of palladacyclces, see: Dupont J, Consorti CS, Spencer J. Chem. Rev. 2005; 105: 2527
• 5a Gandeepan P, Parthasarathy K, Cheng C.-H. J. Am. Chem. Soc. 2010; 132: 8569
• 5b Mousseau JJ, Vallée F, Lorion MM, Charette AB. J. Am. Chem. Soc. 2010; 132: 14412
• 5c Zhang H.-j, Wei J, Zhao F, Liang Y, Wang Z, Xi Z. Chem. Commun. 2011; 46: 7439
• 5d Furuta T, Kitamura Y, Hashimoto A, Fujii S, Tanaka K, Kan T. Org. Lett. 2007; 9: 183
• 5e Wang G.-W, Yuan T.-T, Li D.-D. Angew. Chem. Int. Ed. 2011; 50: 1380 ; Angew. Chem. 2011, 123, 1416
• 5f Satyanarayana G, Maier ME. Org. Lett. 2008; 10: 2361
• 5g Satyanarayana G, Maier ME. Eur. J. Org. Chem. 2008; 5543
• 5h Mahendar L, Krishna J, Reddy AG. K, Ramulu BV, Satyanarayana G. Org. Lett. 2012; 14: 628
• 6a Reddy AG. K, Krishna J, Satyanarayana G. Synlett 2011; 1756
• 6b Krishna J, Reddy AG. K, Mahendar L, Ramulu BV. Synlett 2012; 23: 375
• 6c Suchand B, Krishna J, Ramulu BV, Dibyendu D, Reddy AG. K, Mahendar L. Tetrahedron Lett. 2012; 53: 3861
• 6d Reddy AG. K, Satyanarayana G. Tetrahedron 2012; 68: 8003
• 6e Reddy AG. K, Krishna J, Satyanarayana G. Tetrahedron Lett. 2012; 53: 5635
• 7a Chia Y.-C, Yeh H.-C, Yeh Y.-T, Chen C.-Y. Chem. Nat. Compd. 2011; 47: 220
• 7b Chen C.-Y, Yang W.-L, Hsui Y.-R. Nat. Prod. Res. 2010; 24: 423
• 7c Nakagawa-Goto K, Jung MK, Hamel E, Wu C.-C, Bastow KF, Brossi A, Ohta S, Lee K.-H. Heterocycles 2005; 65: 541
• 8 Choi YL, Yu C.-M, Kim BT, Heo J.-N. J. Org. Chem. 2009; 74: 3948
• 9 Lablanc M, Fagnou K. Org. Lett. 2005; 7: 2849
• 10 Takada T, Arisawa M, Gyoten M, Hamada R, Tohma H, Kita Y. J. Org. Chem. 1999; 63: 7698
• 11 Djurdjevic S, Green RR. Org. Lett. 2007; 9: 5505
• 12a Weitzberg M, Abu-Shakra E, Azeb A, Aizenshtat Z, Blum J. J. Org. Chem. 1987; 52: 529
• 12b Ghera E, Gaoni Y, Shoua S. J. Am. Chem. Soc. 1976; 98: 3627
• 12c Boyé O, Brossi A. Can. J. Chem. 1992; 70: 1237
• 12d Rapoport H, Williams AR, Cisney ME. J. Am. Chem. Soc. 1951; 73: 1414
• 12e Seganish WM, DeShong P. Org. Lett. 2006; 8: 3951
• 12f Besong G, Billen D, Dager I, Kocienski P, Sliwinski E, Tai LR, Boyle FT. Tetrahedron 2008; 64: 4700
• 12g Hackelöer K, Waldvogel SR. Tetrahedron Lett. 2012; 53: 1579
• 13 Crystal data for 3g: CCDC 910650.
• 14a Willis MC, Taylor D, Gillmore AT. Org. Lett. 2004; 6: 4755
• 14b Carril M, SanMartin R, Domínguez E, Tellitu I. Tetrahedron 2007; 63: 690
• 14c Palucki M, Buchwald SL. J. Am. Chem. Soc. 1997; 119: 11108
• 14d Ahman J, Wolfe PJ, Troutman MV, Palucki M, Buchwald SL. J. Am. Chem. Soc. 1998; 120: 1918
• 14e Kawatsura M, John FJ. J. Am. Chem. Soc. 1999; 121: 1473
• 14f Fox JM, Huang X, Chieffi A, Buchwald SL. J. Am. Chem. Soc. 2000; 122: 1360
• 14g Willis MC, Taylor D, Gillmore AT. Tetrahedron 2006; 62: 11513

For reviews of intermediate palladium species with higher oxidation states, see:
• 15a Muñiz K. Angew. Chem. Int. Ed. 2009; 48: 9412 ; Angew. Chem. 2009, 121, 9576
• 15b Desai LV, Malik HA, Sanford MS. Org. Lett. 2006; 8: 1141
• 15c Xu L.-M, Li B.-J, Yang Z, Shi Z.-J. Chem. Soc. Rev. 2010; 39: 712
• 15d Canty AJ. Platinum Metals Rev. 1993; 37: 2
• 16a Quan LG, Gevorgyan V, Yamamoto Y. J. Am. Chem. Soc. 1999; 121: 3545
• 16b Solé D, Vallverdú L, Solans X, Font-Bardía M, Bonjoch J. J. Am. Chem. Soc. 2003; 125: 1587
• 16c Zhao Y.-B, Mariampillai B, Candito DA, Laleu B, Li M, Lautens M. Angew. Chem. Int. Ed. 2009; 48: 1849; Angew. Chem. 2009, 121, 1881
• 16d Solé D, Serrano O. Angew. Chem. Int. Ed. 2007; 46: 7270 ; Angew. Chem. 2007, 119, 7408
• 17 General Procedure-1 for the Pd-Mediated Cyclization (GP-1) In an oven-dried Schlenk tube under nitrogen atmosphere were added ortho-bromoacetophenone 1a–g (100–150 mg, 0.30–0.58 mmol), Pd(OAc)₂ (2 mol%), Xantphos (4 mol%), and K₃PO₄ (0.60–1.16 mmol) followed by addition of dry DMF (2 mL). The resulted reaction mixture was stirred at 150 °C for 0.75–2 h. Progress of the reaction was monitored by TLC until the reaction was completed. The reaction mixture was then quenched with sat. aq NH₄Cl, and the aqueous layer was extracted with EtOAC (3 × 20 mL). The combined organic layers were dried (Na₂SO₄) and concentrated in vacuo. The crude product 3a–g was purified by column chromatography on silica gel using PE–EtOAc as eluent. Representative Analytical Data
  7-Methyl-5H-dibenzo[a,c][7]annulen-5-one (3a) Yield: 25 mg, 45%; viscous liquid. IR (MIR-ATR, 4000–600 cm^–1): ν_max = 3062, 2957, 2853, 1652, 1593, 1439, 1377, 1356, 1307, 1250, 1121, 1003, 850, 771, 735, 621 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.79 (dd, 2 H, J = 7.6, 5.3 Hz, ArH), 7.74 (m, 2 H, ArH), 7.63 (ddd, 1 H, J = 8.7, 7.4, 1.3 Hz, ArH), 7.53 (dd, 1 H, J = 7.7, 7.6 Hz, ArH), 7.48 (2 H, J = Hz, ArH), 6.62 (s, 1 H, ArH), 2.44 (s, 3 H, CH=CCH ₃). ¹³C NMR (100 MHz, CDCl₃): δ = 194.0 (s, ArC=O), 144.8 (s, CH=CCH₃), 142.0 (s, ArC), 137.5 (s, ArC), 137.3 (s, ArC), 135.7 (s, ArC), 133.2 (d, ArCH), 131.9 (d, CH=CCH₃), 131.2 (d, ArCH), 130.8 (d, ArCH), 128.6 (d, ArCH), 128.1 (d, ArCH), 127.8 (d, ArCH), 127.3 (d, ArCH), 127.1 (d, ArCH), 24.4 (q, CH=CCH ₃). HRMS (ESI⁺): m/z calcd for [C₃₂H₂₅O₂]⁺ = [2 (M + H)]⁺: 441.1849; found: 441.1836. 3,9-Dimethoxy-7-methyl-5H-dibenzo[a,c][7]annulen-5-one (3c) Yield: 31 mg, 50%; white solid; mp 125–127 °C. IR (MIR-ATR, 4000–600 cm^–1): ν_max = 3001, 2934, 2837, 1643, 1603, 1571, 1484, 1408, 1337, 1281, 1240, 1174, 1039, 814, 753, 722, 614 cm^–1. ¹H NMR (400 MHz CDCl₃): δ = 7.69 (d, J = 8.9 Hz, ArH), 7.66 (d, J = 8.9 Hz, ArH), 7.28 (d, 1 H, J = 2.9 Hz, ArH), 7.20 (d, 1 H, J = 2.8 Hz, ArH), 7.18 (dd, 1 H, J = 8.9, 2.9 Hz, ArH), 7.04 (dd, 1 H, J = 8.9, 2.8 Hz, ArH), 6.61 (d, 1 H, J = 0.9 Hz, ArH), 3.89 (s, 3 H, ArOCH₃), 3.89 (s, 3 H, ArOCH₃), 2.43 (d, 3 H, J = 0.9 Hz, CH=CCH ₃). ¹³C NMR (100 MHz, CDCl₃): δ = 193.6 (s, ArC=O), 159.0 (s, ArC), 158.4 (s, ArC), 144.8 (s, CH=CCH₃), 142.3 (s, ArC), 136.3 (s, ArC), 132.9 (d, CH=CCH₃),132.8 (d, ArCH), 131.3 (d, ArCH), 130.5 (s, ArC), 130.4 (s, ArC), 119.4 (d, ArCH), 114.5 (d, ArCH), 112.2 (d, ArCH), 109.7 (d, ArCH), 55.6 (q, ArOCH₃), 55.4 (q, ArOCH₃), 24.6 (q, CH=CCH₃). HRMS (ESI+): m/z calcd for [C₁₈H₁₇O₃]⁺ = [M + H]⁺: 281.1172; found: 281.1161.