Lewis Acid Catalyzed Synthesis of Allocolchicinoids

This paper is dedicated to Manfred Schlosser, in recognition of his many contributions to organic chemistry but with particular admiration for his work in remote functionalization by way of organometallic intermediates.

Abstract

The Lewis acid catalyzed intramolecular conjugate addition of 3′,4′,5′-trimethoxybiphenyl-2-propenones give the corresponding 8,9,10-trimethoxydibenzocycloheptanones in good yields. A case of a conjugate addition–cation rearrangement of a 2′,3′,4′-trimethoxybiphenyl-2-propenone to give the same ring system is also reported. The dibenzocycloheptanones may be converted readily into the 8,9,10-trimethoxy-substituted allocolchicinoids in highly enantioenriched form.

Key words

Lewis acids - catalysis - Michael addition - cyclization - antitumor agents

• References and Notes

• 1a Tojo E, Abu Zarga MH, Freyer AJ, Shamma M. J. Nat. Prod. 1989; 52: 1163
• 1b Al-Tel TH, Abu Zarga MH, Sabri SS, Freyer AJ, Shamma M. J. Nat. Prod. 1990; 53: 623
• 1c Abu Zarga MH, Sabri S, Al-Tel TH, Atta-ur-Rahman Shah Z, Feroz M. J. Nat. Prod. 1991; 54: 936
• 1d See also: Yusupov MK, Sadykov AS. J. Gen. Chem. USSR (Engl. Transl.) 1964; 34: 1686; Zh. Obshch. Khim. 1964, 34, 1677
• 1e Baudoin O, Guéritte R In Studies in Natural Products Chemistry . Vol. 29. Atta-ur-Rahman Elsevier; Amsterdam: 2003: 355-417
• 1f Banwell MG, Fam M.-A, Gable RW, Hamel E. J. Chem. Soc., Chem. Commun. 1994; 2647
• 2 In addition, suhailamine has been assigned the structure of allocolchicine incorrectly (see ref. 1f).
• 3a Iorio MA. Heterocycles 1984; 22: 2207
• 3b Brecht R, Haenel F, Seitz G. Liebigs Ann./Recl. 1997; 2275
• 3c Diler U, Franz B, Roettele H, Schroeder G, Herges R. J. Prakt. Chem./Chem.-Zeit. 1998; 340: 468
• 3d Bergemann S, Brecht R, Büttner F, Guénard D, Gust R, Seitz G, Stubbs MT, Thoret S. Bioorg. Med. Chem. 2003; 11: 1269
• 4a Tang-Wei DF, Brossi A, Arnold LD, Gross P. Heterocycles 1994; 39: 385
• 4b Guan J, Zhu X, Brossi A, Tachibana Y, Bastow KF, Verdier-Pinard P, Hamel E, McPhail AT, Lee K. Coll. Czech. Chem. Commun. 1999; 64: 217
• 4c Nakagawa-Goto K, Jung MK, Hamel E, Wu C.-C, Bastow KF, Brossi A, Ohta S, Lee K.-H. Heterocycles 2005; 65: 541
• 4d Davis PD, Dougherty GJ, Blakey DC, Galbraith SM, Tozer GM, Holder AL, Naylor MA, Nolan J, Stratford MR. L, Chaplin DJ, Hill SA. Cancer Res. 2002; 62: 7247
• 5a Perez-Ramirez B, Andreu JM, Gorbunoff MJ, Timasheff SN. Biochemistry 1996; 35: 3277
• 5b Brecht R, Seitz G, Guénard D, Thoret S. Bioorg. Med. Chem. 2000; 8: 557
• 5c Polański J. Acta Biochim. Pol. 2000; 47: 37
• 5d Han S, Hamel E, Bastow KF, McPhail AT, Brossi A, Lee K.-H. Bioorg. Med. Chem. Lett. 2002; 12: 2851
• 5e Büttner F, Bergemann S, Guénard D, Gust R, Seitz G, Thoret S. Bioorg. Med. Chem. 2005; 13: 3497
• 5f Boyer F.-D, Dubois J, Thoret S, Tran Huu Dau M.-E, Hanna I. Bioorg. Chem. 2010; 28: 149
• 6 Lippert JW. III. Bioorg. Med. Chem. 2007; 15: 605
• 7 For a review, see: Sitnikov NS, Fedorov AYu. Russ. Chem. Rev. 2013; 82: 393

For racemic syntheses and those based on resolution, see refs. 7, 1f, and:
• 8a Cook JW, Jack J, Loudon JD, Buchanan GL, MacMillan J. J. Chem. Soc. 1951; 1397
• 8b Sawyer JS, Macdonald TL. Tetrahedron Lett. 1988; 29: 4839
• 8c Boyé O, Brossi A, Yeh HJ. C, Hamel E, Wegrzynski B, Toome V. Can. J. Chem. 1992; 70: 1237
• 9 Vorogushin AV, Predeus AW, Wulff WD, Hansen H.-J. J. Org. Chem. 2003; 68: 5826
• 10a Wu TR, Chong JM. Org. Lett. 2006; 8: 15
• 10b Besong G, Jarowicki K, Kocienski PJ, Sliwinski E, Boyle FT. Org. Biomol. Chem. 2006; 4: 2193
• 10c Broady SD, Golden MD, Leonard J, Muir JC, Maudet M. Tetrahedron Lett. 2007; 48: 4627
• 11 Leblanc M, Fagnou K. Org. Lett. 2005; 7: 2849
• 12 Beshong G, Billen D, Dager I, Kocienski P, Sliwinski E, Tai LR, Boyle FT. Tetrahedron 2008; 64: 4700
• 13a Djurdjevic S, Yang F, Green JR. J. Org. Chem. 2010; 75: 8241
• 13b Djurdjevic S, Green JR. Org. Lett. 2007; 9: 5505

For recent examples, see ref. 5f and:
• 14a Sitnikov NS, Kokishena AS, Fukin GK, Neudörfl J.-M, Sutorius H, Prokop A, Fokin VW, Schmalz H.-G, Fedorov AY. Eur. J. Org. Chem. 2014; 6481
• 14b Kuznetsova NR, Svirshchevskaya EV, Sitnikov NS, Abodo L, Sutorius H, Zapke J, Velder J, Thomopoulou P, Oschkinat H, Prokop A, Schmalz H.-G, Fedorov AYu, Vodovozoya EL. Russ. J. Bioorg. Chem. 2013; 39: 543
• 14c Sitnikov N, Velder J, Abodo L, Cuvelier N, Neudörfl J, Prokop A, Krause G, Fedorov AY, Schmalz H.-G. Chem. Eur. J. 2012; 18: 12096
• 14d Bhowmik S, Khanna S, Srivastava K, Hasanain M, Sarkar J, Verma S, Batra S. ChemMedChem 2008; 3: 1767
• 14e Nicolaus N, Reball J, Sitkikov N, Velder J, Termath A, Fedorov AY, Schmalz H.-G. Heterocycles 2011; 82: 1585
• 14f Chosson E, Santoro F, Rochais C, Sopkova-de Oliveira Santos J, Legay R, Thoret S, Cresteil T, Sinicropi MS, Besson T, Dallemagne P. Bioorg. Med. Chem. 2012; 20: 2614
• 14g Vorogushin AV, Wulff WD, Hansen H.-J. Tetrahedron 2008; 64: 949 ; and references cited therein
• 14h Boyer F.-D, Hanna I. Eur. J. Org. Chem. 2008; 4938
• 14i For earlier examples, see ref. 7.

For more remotely related systems, see:
• 15a Nicolaus N, Schmalz H.-G. Synlett 2010; 2071
• 15b Usanov DL, Nadovic M, Brasholz M, Tamamoto H. Helv. Chim. Acta 2012; 95: 1773
• 16 Larocque K, Ovadje P, Djurdjevic S, Mehdi M, Green J, Pandey S. PLoS One 2014; 9: e87064
• 17a Majetich G, Zhang Y, Feltman TL, Belfoure V. Tetrahedron Lett. 1997; 34: 441
• 17b Majetich G, Zhnag Y, Feltman TL, Duncan SJ. Tetrahedron Lett. 1997; 34: 445
• 17c Majetich G, Hicks R, Zhang Y, Tian X, Feltman TL, Fang J, Duncan SJr. J. Org. Chem. 1996; 61: 8169
• 17d Majetich G, Li Y, Zou G. Heterocycles 2007; 73: 217
• 17e Majetich G, Yu J, Li Y. Heterocycles 2007; 73: 227
• 17f Majetich G, Zou G, Grive J. Org. Lett. 2008; 10: 85
• 17g Majetch G, Grove JL. Org. Lett. 2009; 11: 2904
• 17h Majetich G, Zhang Y, Tian X, Britton JE, Li Y, Phillips R. Tetrahedron 2011; 67: 10129
• 17i Majetich G, Zou G, Hu S. Can. J. Chem. 2012; 90: 75
• 18 Chen Y, Huang C, Liu X, Perl E, Chen Z, Namgung J, Subramanian G, Zhang G, Hersh WH. J. Org. Chem. 2014; 79: 3452
• 19 General Procedure A dilute solution of α,β-unsaturated ketone compound 10a–g in anhydrous CH₂Cl₂ (c 0.002 M) was cooled to 0 °C. A solution of BF₃·OEt₂ (cat. loading 5 mol%) in CH₂Cl₂ was then added slowly to the reactant solution. The mixture was allowed to warm to r.t. and monitored by TLC. Upon the complete consumption of the starting material (4–72 h), a sat. solution of NaHCO₃ was added and the mixture subjected to a conventional extractive workup (CH₂Cl₂). The volatiles were removed under reduced pressure, and the residue was purified by flash chromatography to afford the tricyclic ketone products 11a–f.
• 20 Selected Characterization Data (for Complete Data, See Supporting Information) Compound 11b: IR (neat): ν_max = 2958, 2923, 2853, 1679, 1455, 1259, 1109, 1019, 800 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.56–7.62 (m, 2 H), 7.40–7.43 (m, 2 H), 6.73 (s, 1 H), 3.93 (s, 3 H), 3.89 (s. 3 H), 3.88 (s, 3 H), 2.92–3.00 (m, 4 H). ¹³C NMR (125 MHz, CDCl₃): δ = 206.8, 152.4, 150.3, 142.2, 139.0, 138.8, 134.7, 132.0, 129.1, 128.4, 127.8, 125.6, 109.4, 61.5, 61.0, 56.2, 47.7, 20.6. MS: m/e = 298 [M⁺]. HRMS: m/e calcd for C₁₈H₁₈O₄: 298.1205; found: 298.1200. Compound 11c: IR (neat): ν_max = 2928, 1851, 1675, 1600, 1453, 1411, 1108, 1008, 699 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.46 (m, 2 H), 7.41 (t, J = 7.3 Hz, 2 H), 7.35–7.37 (m, 2 H), 7.24 (d, J = 3.0 Hz, 1 H), 7.19 (dd, J = 3.0, 8.5 Hz, 1 H), 6.69 (s, 1 H), 5.13 (s, 2 H), 3.92 (s, 3 H), 3.89 (s, 3 H), 3.88 (s, 3 H), 2.92–3.00 (m, 4 H). ¹³C NMR (125 MHz, CDCl₃): δ = 206.3, 158.3, 152.3, 150.3, 141.8, 139.9, 136.5, 134.5, 131.8, 130.7, 128.7, 128.2, 127.6, 125.4, 119.6, 113.3, 109.2, 70.2, 61.5, 61.0, 56.2, 47.5, 29.7, 20.6. MS: m/e = 404 [M⁺]. HRMS: m/e calcd for C₂₅H₂₄O₅: 404.1624; found: 404.1621. Compound 11d: IR (neat): ν_max = 2922, 2851, 1730, 1655, 1498, 1478, 1457, 1250, 1101, 1021 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.12 (s, 1 H), 6.88 (s, 1 H), 6.65 (s, 1 H), 6.06 (s, 2 H), 3.92 (s, 3 H), 3.88 (s, 3 H), 3.87 (s, 3 H), 2.97 (m, 2 H), 2.87 (m, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 204.9, 152.3, 150.9, 150.1, 147.3, 142.0, 134.9, 134.4, 133.1, 125.7, 109.4, 109.1, 108.6, 101.9, 61.4, 60.9, 56.2, 47.3, 20.6. MS: m/e = 342 [M⁺]. HRMS: m/e calcd for C₁₉H₁₈O₆: 342.1103; found: 342.1105. Compound 15g: IR (neat): ν_max = 3266, 2928, 1720, 1643, 1298, 1103, 1012 cm^–1. ¹H NMR (500 MHz, DMSO-d ₆): δ = 8.61 (d, J = 8.5 Hz, 1 H), 7.95 (m, 2 H), 7.55 (d, J = 7.5 Hz, 1 H), 6.93 (s, 1 H), 4.52 (m, 1 H), 3.86 (s, 3 H), 3.80 (s, 3 H), 3.79 (s, 3 H), 2.92 (m, 1 H), 2.18 (m, 1 H), 1.97 (m, 1 H), 1.88 (s, 3 H), 1.77 (m, 1 H). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 169.1, 166.8, 152.3, 150.9, 143.8, 142.4, 141.1, 134.7, 129.1, 129.0, 128.4, 124.8, 124.6, 109.0, 62.1, 61.0, 56.4, 52.8, 48.9, 26.0, 23.2, 22.2. MS: m/e = 399 [M⁺]. HRMS: m/e calcd for C₂₂H₂₅NO₆: 399.1682; found: 399.1675.
• 21a Pearson RG. Inorg. Chem. 1998; 27: 734
• 21b Yamaguchi M, Nishimura Y. Chem. Commun. 2008; 35
• 21c Amemiya R, Yamaguchi M. Eur. J. Org. Chem. 2005; 5145
• 21d Barman DC. Synlett 2003; 2440
• 21e Inoue H, Chatani N, Murai S. J. Org. Chem. 2002; 67: 1414
• 22 For an example of Ga³⁺-catalyzed ynone conjugate additions, see: Yadav JS, Subba Reddy BV, Gupta MK, Dash U, Pandey SK. Synlett 2007; 809
• 23 GaCl₃ showed some success in the 10a–13a transformation (5 mol%, 48 h, 67% conversion; 10 mol%, 3 h, 52% yield).
• 24 Newman MF. Acc. Chem. Res. 1972; 5: 354
• 25a Suri JT, Vu T, Hernandez A, Congdon J, Singaram B. Tetrahedron Lett. 2002; 43: 3649
• 25b Cordes DB, Nguyen TM, Kwong TJ, Suri JT, Luibrand RT, Singaram B. Eur. J. Org. Chem. 2005; 5289