Concise Synthesis of Arylnaphthalene Lignans by Regioselective Intra­molecular Anionic Diels–Alder Reactions of 1,7-Diaryl-1,6-diynes

Abstract

Total synthesis of phyllamycin A and C, justicidin B, and retrojusticidin B from simple arylalkynyl alcohols and (3,4-methylenedioxyphenyl)propynal was accomplished in 4–5 steps by employing an intramolecular anionic Diels–Alder reaction as the key step.

Key words

lignan - natural products - total synthesis - Diels–Alder reaction - carbanions

• References and Notes

• 1 Ward RS. Nat. Prod. Rep. 1999; 16: 75
• 2 Asano J, Chiba K, Tada M, Yoshii T. Phytochemistry 1996; 42: 713
• 3a Baba A, Oda T, Taketomi S, Notoya K, Nishimura A, Sohoa T. Chem. Pharm. Bull. 1999; 47: 369
• 3b Baba A, Kawamura N, Makino H, Ohta Y, Taketomi S, Sohoa T. J. Med. Chem. 1996; 39: 5176
• 4 Chang CW, Lin MT, Lee SS, Liu KC. S. C, Hsu FL, Lin JY. Antiviral Res. 1995; 27: 367
• 5a Heller HG, Strydom PJ. J. Chem. Soc., Chem. Commun. 1976; 50
• 5b Brown E, Daugan A. Tetrahedron 1989; 45: 141
• 5c Flanagan SR, Harrowven DC, Bradley M. Tetrahedron 2002; 58: 5989
• 6a Seko S, Tanabe Y, Suzukamo G. Tetrahedron Lett. 1990; 31: 6883
• 6b Nishii Y, Yoshida T, Asano H, Wakasugi K, Morita J, Aso Y, Yoshida E, Motoyoshiya J, Aoyama H, Tanabe Y. J. Org. Chem. 2005; 70: 2667
• 7a Meyers AI, Fiisak JR, Aitken RA. J. Am. Chem. Soc. 1981; 103: 5446
• 7b Andrews RC, Teague SJ, Meyers AI. J. Am. Chem. Soc. 1988; 110: 7854
• 8a Ziegler FE, Schwartz JA. J. Org. Chem. 1978; 43: 985
• 8b Gonzalez AG, Perez JP, Turujillo M. Tetrahedron 1978; 34: 1011
• 8c Pelter A, Ward RS, Pritchard MC, Kay IT. J. Chem. Soc., Perkin Trans. 1 1988; 1603
• 8d Ogiku T, Seki M, Takahashi M, Ohmizu H, Iwasaki T. Tetrahedron Lett. 1990; 31: 5487
• 8e Harrowven DC. Tetrahedron Lett. 1991; 32: 3735
• 8f Ogiku T, Yoshida S, Ohmizu H, Iwasaki T. J. Org. Chem. 1995; 60: 4585
• 9a Sato Y, Tamura T, Mori M. Angew. Chem. Int. Ed. 2004; 43: 2436
• 9b Sato Y, Tamura T, Kinbara A, Mori M. Adv. Synth. Catal. 2007; 349: 647
• 10 Gudla V, Balamurugan R. J. Org. Chem. 2011; 76: 9919
• 11a Klemm LH, Gopinath KW, HsuLee D, Kelly FW, Trod E, Mcguire TM. Tetrahedron 1966; 22: 1797
• 11b Holmes TL, Stevenson R. J. Org. Chem. 1971; 36: 3450
• 11c Block K, Stevenson R. J. Org. Chem. 1971; 36: 3453
• 11d Stevenson R, Weber JV. J. Nat. Prod. 1989; 52: 367
• 11e Eghbali N, Eddy J, Anastas PT. J. Org. Chem. 2008; 73: 6932
• 11f Foley P, Eghbali N, Anastas PT. Green Chem. 2010; 12: 888
• 12a Takano S, Otaki S, Ogasawara K. Tetrahedron Lett. 1985; 26: 1659
• 12b Cochran JE, Padwa A. J. Org. Chem. 1995; 60: 3938
• 12c Padwa A, Cochran JE, Kappe CO. J. Org. Chem. 1996; 61: 3706
• 13 Kudoh T, Mori T, Shirahama M, Yamada M, Ishikawa T, Saito S, Kobayashi H. J. Am. Chem. Soc. 2007; 129: 4939
• 14a Sonogashira K In Comprehensive Organic Synthesis . Vol. 3. Trost BM, Fleming I. Pergamon Press; Oxford: 1991: 521
• 14b Bleicher L, Cosford ND. P. Synlett 1995; 1115
• 15a Lin M, Lee S, Liu KC. S. C. J. Nat. Prod. 1995; 58: 244
• 15b Lee S, Lin M, Liu C, Lin Y, Liu KC. S. C. J. Nat. Prod. 1996; 59: 1061
• 16 General Procedure for the Intramolecular Anionic Diels–Alder Reaction of 7a To a solution of 7a (444 mg, 1.08 mmol) in DMSO (6 mL) was added Triton B (40 wt% in MeOH) (0.6 mL, 120 mol%) at r.t. The mixture was stirred at r.t. for 24 h. After completed the reaction, sat. NH₄Cl aq solution was added to this and extracted with hexane–EtOAc (3:1). The combined organic layers were dried over MgSO₄, filtered, and concentrated by a rotary evaporator. The residue was purified by column chromatography to afford cycloadduct 8a (408 mg, 92%).
• 17 Analytical Data for Phyllamycin C (1) Mp 193.8–194.3 °C; R_f = 0.57 (1:1 hexane–EtOAc). ¹H NMR (300 MHz, CDCl₃): δ = 3.79 (s, 3 H), 4.02 (s, 3 H), 4.08 (s, 3 H), 5.412 (s, 1 H), 5.416 (s, 1 H), 6.05 (d, 1 H, J = 1.7 Hz), 6.11 (d, 1 H, J = 1.7 Hz), 6.82 (dd, 1 H, J = 1.6, 7.7 Hz), 6.85 (d, 1 H, J = 1.6 Hz), 6.93 (s, 1 H), 6.97 (d, 1 H, J = 7.7 Hz), 8.13 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 55.8, 61.1, 61.5, 68.2, 101.2, 102.3, 108.1, 110.5, 114.0, 120.0, 123.4, 128.25, 128.33, 130.4, 138.6, 139.7, 143.1, 147.3, 147.5, 147.6, 153.4, 169.7. IR (KBr): 2940, 1768, 1476, 1227, 1058 cm^–1. Analytical Data for Phyllamycin A (2) Mp 231.4–231.3 °C. R_f = 0.63 (3:1 hexane–EtOAc). ¹H NMR (300 MHz, CDCl₃): δ = 3.83 (s, 3 H), 3.99 (s, 3 H), 4.10 (s, 3 H), 5.21 (s, 2 H), 6.07 (d, 1 H, J = 1.4 Hz), 6.10 (d, 1 H, J = 1.4 Hz), 6.80–6.83 (m, 2 H), 6.88 (s, 1 H), 6.98 (d, 1 H, J = 8.2 Hz), 8.74 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 55.8, 61.1, 61.6, 69.3, 100.2, 101.4, 108.9, 109.5, 120.5, 120.8, 122.7, 125.5, 129.6, 131.9, 132.9, 139.2, 141.1, 147.7, 148.3, 149.1, 155.6, 171.4. IR (KBr): 2941, 1767, 1482, 1234, 1027 cm^–1. Analytical Data for Justicidin B (3) R_f = 0.23 (1:1 hexane–EtOAc). ¹H NMR (300 MHz, CDCl₃): δ = 3.82 (s, 3 H), 4.05 (s, 3 H), 5.380 (s, 1 H), 5.384 (s, 1 H), 6.05 (d, 1 H, J = 1.6 Hz), 6.10 (d, 1 H, J = 1.6 Hz), 6.83 (dd, 1 H, J = 8.0, 1.7 Hz), 6.86 (d, 1 H, J = 1.7 Hz), 6.97 (d, 1 H, J = 8.0 Hz), 7.11 (s, 1 H), 7.19 (s, 1 H), 7.70 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 55.8, 56.0, 68.0, 101.2, 106.0, 106.1, 108.2, 110.6, 118.2, 118.6, 123.5, 128.5, 128.9, 133.2, 139.5, 139.7, 147.6 × 2, 150.2, 151.9, 169.8. IR (KBr): 2938, 1754, 1506, 1238, 1158, 1036 cm^–1. Analytical Data for Retrojusticidin B (4) Mp 224.0–223.5 °C; R_f = 0.40 (1:1 hexane–EtOAc). ¹H NMR (300 MHz, CDCl₃): δ = 3.85 (s, 3 H), 4.05 (s, 3 H), 5.21 (s, 2 H), 6.07 (d, 1 H, J = 1.4 Hz), 6.11 (d, 1 H, J = 1.4 Hz), 6.82–6.85 (m, 2 H), 6.99 (d, 1 H, J = 8.5 Hz), 7.09 (s, 1 H), 7.29 (s, 1 H), 8.30 (s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 55.8, 55.9, 69.3, 101.4, 104.1, 107.7, 108.9, 109.5, 121.4, 122.7, 124.0, 129.7, 129.9, 131.6, 131.9, 137.9, 147.6, 148.3, 150.2, 152.2, 171.3. IR (KBr) 2923, 1751, 1505, 1231 cm^–1.