Superacid-Promoted Dual C–C Bond Formation by Friedel–Crafts Alkylation and Acylation of Ethyl Cinnamates: Synthesis of Indanones

Dedicated to the memory of my mentor Prof. A. Srikrishna (1955–2013), an outstanding organic chemist and a constant source of inspiration.

Abstract

A superacid (triflic acid) promoted dual C–C bond formation via intermolecular Friedel–Crafts alkylation (Michael addition type) and intramolecular acylation for the efficient synthesis of 3-substituted indan-1-ones is presented. This method was successful in activating ethyl cinnamates towards dual aromatic electrophilic substitution. Moreover, it enabled us to synthesize novel spirotetracyclic systems.

Key words

cinnamates - indanones - Friedel–Crafts alkylation - ­acylation - superacid

• References and Notes

• 1 Friedel C, Crafts JM. C. R. Hebd. Seances Acad. Sci. 1877; 84: 1450

For reviews, see:
• 2a Kobayashi S, Sugiura M, Kitagawa H, Lam WW.-L. Chem. Rev. 2002; 102: 2227
• 2b Poulsen TB, Jørgensen KA. Chem. Rev. 2008; 108: 2903
• 2c Sartori JM, Maggi R. Chem. Rev. 2011; 111: 181
• 2d Rueping M, Nachtsheim BJ. Beilstein J. Org. Chem. 2010; 6: No. 6
• 2e Shi M, Lu J.-M, Wei Y, Shao L.-X. Acc. Chem. Res. 2012; 45: 641
• 3a Gore PH In Friedel–Crafts and Related Reactions . Olah GA. John Wiley and Sons; London: 1964. Part 1 Vol. III. 1
• 3b Olah GA, Klumpp DA. Superelectrophiles and Their Chemistry . Wiley; New York: 2008
• 4a Sai KK. S, Tokarz MJ, Malunchuk AP, Zheng C, Gilbert TM, Klumpp DA. J. Am. Chem. Soc. 2008; 130: 14388
• 4b Zhang Y, Sheets MR, Raja EK, Boblak KN, Klumpp DA. J. Am. Chem. Soc. 2011; 133: 8467
• 4c Evans DA, Fandrick KR. Org. Lett. 2006; 8: 2249
• 4d Rose MD, Cassidy MP, Rashatasakhon P, Padwa A. J. Org. Chem. 2007; 72: 538
• 4e Wu Y.-C, Liu L, Liu Y.-L, Wang D, Chen Y.-J. J. Org. Chem. 2007; 72: 9383
• 5a Suzuki T, Ohwada T, Shudo K. J. Am. Chem. Soc. 1997; 119: 6774
• 5b Ohwada T, Suzuki T, Shudo K. J. Am. Chem. Soc. 1998; 120: 4629
• 5c Kurouchi H, Sugimoto H, Otani Y, Ohwada T. J. Am. Chem. Soc. 2010; 132: 807
• 5d Colquhoun HM, Lewis DF, Williams DJ. Org. Lett. 2001; 3: 2337
• 5e Fillion E, Fishlock D. Org. Lett. 2003; 5: 4653
• 5f Wang Q, Padwa A. Org. Lett. 2006; 8: 601
• 5g Chassaing S, Kumarraja M, Pale P, Sommer J. Org. Lett. 2007; 9: 3889
• 5h Saito A, Umakoshi M, Yagyu N, Hanzawa Y. Org. Lett. 2008; 10: 1783
• 5i Tang S, Xu Y, He J, He Y, Zheng J, Pan X, She X. Org. Lett. 2008; 10: 1855
• 5j Kangani CO, Day BW. Org. Lett. 2008; 10: 2645
• 5k Kim K, Kim I. Org. Lett. 2010; 12: 5314
• 5l Chinnagolla RK, Jeganmohan M. Org. Lett. 2012; 14: 5246
• 5m Eom D, Park S, Park Y, Ryu T, Lee PH. Org. Lett. 2012; 14: 5392
• 5n Klumpp DA, Baek DN, Prakash GK. S, Olah GA. J. Org. Chem. 1997; 62: 6666
• 5o Rendy R, Zhang Y, McElrea A, Gomez A, Klumpp DA. J. Org. Chem. 2004; 69: 2340
• 5p Bhar SS, Ramana MM. V. J. Org. Chem. 2004; 69: 8935
• 5q Womack GB, Angeles JG, Fanelli VE, Heyer CA. J. Org. Chem. 2007; 72: 7046
• 5r Sai KK. S, Esteves PM, Penha ET. D, Klumpp DA. J. Org. Chem. 2008; 73: 6506
• 5s Prakash GK. S, Paknia F, Vaghoo H, Rasul G, Mathew T, Olah GA. J. Org. Chem. 2010; 75: 2219
• 5t Raja EK, DeSchepper DJ, Lill SO. N, Klumpp DA. J. Org. Chem. 2012; 77: 5788
• 5u Choi YL, Kim BT. Heo J.-N. J. Org. Chem. 2012; 77: 8762
• 5v Mahoney SJ, Moon DT, Hollinger J, Fillion E. Tetrahedron Lett. 2009; 50: 4706
• 5w Aikawa H, Tago S, Umetsu K, Haginiwa N, Asao N. Tetrahedron 2009; 65: 1774
• 6 Olah GA, Germain A, Lin HC, Forsyth DA. J. Am. Chem. Soc. 1975; 97: 2928
• 7a Chang YH, Ford WT. J. Org. Chem. 1981; 46: 3758
• 7b Nishimoto Y, Babu SA, Yasuda M, Baba A. J. Org. Chem. 2008; 73: 9465
• 7c Wrona-Piotrowicz A, Cegliński D, Zakrzewski J. Tetrahedron Lett. 2011; 52: 5270
• 7d Fillion E, Fishlock D, Wilsily A, Goll JM. J. Org. Chem. 2005; 70: 1316
• 8 Hwang JP, Prakash GK. S, Olah GA. Tetrahedron 2000; 56: 7199
• 9a Hammett LP. Chem. Rev. 1935; 17: 125
• 9b Hammett LP. J. Am. Chem. Soc. 1937; 59: 96
• 9c King JF, Rathore R, Guo Z, Li M, Payne NC. J. Am. Chem. Soc. 2000; 122: 10308
• 9d Bruckner R. Organic Mechanisms: Reactions, Stereochemistry and Synthesis. Harmata M. Springer; Berlin: 2010
• 10a Hashmi AS. K, Schwarz L, Choi J.-H. Angew. Chem. Int. Ed. 2000; 39: 2285; Angew. Chem. 2000; 112 2382
• 10b Gerald Dyker G, Muth E, Hashmi AS. K, Ding L. Adv. Synth. Catal. 2003; 345: 1247
• 10c Hashmi AS. K, Schwarz L, Rubenbauer P, Blanco MC. Adv. Synth. Catal. 2006; 348: 705
• 11 Ito T, Tanaka T, Iinuma M, Nakaya K.-i, Takahashi Y, Sawa R, Murata J, Darnaedi D. J. Nat. Prod. 2004; 67: 932
• 12 Sugimoto H, Iimura Y, Yamanishi Y, Yamatsu K. J. Med. Chem. 1995; 38: 4821
• 13a Dolling U.-H, Davis P, Grabowski EJ. J. J. Am. Chem. Soc. 1984; 106: 446
• 13b deSolms SJ, Woltersdorf Jr. OW, Cragoe Jr. EJ. J. Med. Chem. 1978; 21: 437
• 14a Banerjee M, Mukhopadhyay R, Achari B, Banerjee AK. J. Org. Chem. 2006; 71: 2787
• 14b Lomberget T, Bentz E, Bouyssi D, Balme G. Org. Lett. 2003; 5: 2055
• 14c Banerjee M, Makhopadhyay R, Achari B, Banerjee AK. Org. Lett. 2003; 5: 3931

For isolation, see:
• 14d Lin W.-H, Fang J.-M, Cheng Y.-S. Phytochemistry 1995; 40: 871
• 15 General Procedure for Friedel–Crafts Alkylation and Acylation of Ethyl Cinnamates (GP-1)To an oven-dried Schlenk tube under nitrogen atmosphere were added ester 1 (100 mg, 0.42–0.57 mmol), arene 2 (in case of benzene, toluene, and xylene 12 equiv and for other electron-rich arenes 1.5 equiv were used for 1 equiv of ester 1) and DCE (2 mL), followed by the addition of TfOH [3 equiv (i.e., 1.26–1.71 mmol)]. The resultant reaction mixture was stirred at 80 °C for 12–24 h. Progress of the reaction was monitored by TLC until the reaction was completed. The reaction mixture was quenched by the addition of aq NaHCO₃ and extracted with CH₂Cl₂ (3 × 20 mL). The combined organic layers were washed with sat. NaCl solution, dried (Na₂SO₄), and concentrated under reduced pressure. Purification of the residue by silica gel column chromatography (PE–EtOAc) furnished the indanone 3 (54–92%).Representative Analytical DataCompound 3f: IR (MIR-ATR, 4000–600 cm^–1): 2966, 2930, 1710, 1602, 1491, 1462, 1288, 1234, 1151, 1093, 1012, 828, 762, 674, 582 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.78 (d, 1 H, J = 7.3 Hz, ArH), 7.60 (dd, 1 H, J = 7.8, 7.3 Hz, ArH), 7.43 (dd, 1 H, J = 7.8, 7.3 Hz, ArH), 7.25 (d, 1 H, J = 7.8 Hz, ArH), 7.24 (ddd, 2 H, J=8.8, 2.4, 2.4 Hz, ArH), 7.10 (ddd, 2 H, J = 8.8, 2.4, 2.4 Hz, ArH), 2.91 (d, 1 H, J = 19.1 Hz, CH_a H_bCO), 2.88 (d, 1 H, J = 19.1 Hz, CH_a H_b CO), 1.81 [s, 3 H, ArC(CH₂CO)CH ₃] ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 205.3 (s, C=O), 162.3 (s, ArC), 145.8 (s, ArC), 135.6 (s, ArC), 135.4 (d, ArCH), 132.3 (s, ArC), 128.5 (d, 2 C, ArCH), 128.0 (d, ArCH), 127.7 (d, 2 C, ArCH), 125.4 (d, ArCH), 123.4 (d, ArCH), 55.5 (t, CH₂CO), 45.6 [s, ArC(CH₂CO)CH₃], 28.3 [q, ArC(CH₂CO)CH₃] ppm. HRMS (APCI⁺): m/z calcd for [C₁₆H₁₄ClO]⁺: 257.0728 [M + H]⁺; found: 257.0724.Compound 3g: IR (MIR-ATR, 4000–600 cm^–1): 2964, 2851, 1705, 1581, 1488, 1399, 1282, 1244, 1160, 1093, 826, 724, 665, 588 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.57 (s, 1 H, ArH), 7.42 (d, 1 H, J = 7.8 Hz, ArH), 7.22 (ddd, 2 H, J = 8.8, 2.4, 2.4 Hz, ArH), 7.14 (d, 1 H, J = 7.8 Hz, ArH), 7.10 (ddd, 2 H, J = 8.8, 2.4, 2.4 Hz, ArH), 2.89 (d, 1 H, J = 19.1 Hz, CH_a H_bCO), 2.87 (d, 1 H, J = 19.1 Hz, CH_a H_b CO), 2.42 (s, 3 H, ArCH₃), 1.78 [s, 3 H, ArC(CH₂CO)CH₃] ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 205.4 (s, C=O), 159.7 (s, ArC), 146.1 (s, ArC), 138.0 (s, ArC), 136.6 (d, ArCH), 135.9 (s, ArC), 132.2 (s, ArC), 128.5 (d, 2 C, ArCH), 127.6 (d, 2 C, ArCH), 125.1 (d, ArCH), 123.3 (d, ArCH), 55.8 (t, CH₂CO), 45.3 [s, ArC(CH₂CO)CH₃], 28.3 [q, ArC(CH₂CO)CH₃], 21.1 (q, ArCH₃) ppm. HRMS (APCI⁺): m/z calcd for [C₁₇H₁₆ClO]⁺: 271.0884 [M + H]⁺; found: 271.0880.