A simple construction of chiral fused benzoxocine ring ethers fromD-glucose by regioselective 8-endo-aryl radical cyclisation

摘要

D-Glucose O O O O O Me Me HO Me Me Br R O O O O O Me Me O Me Me H H R Br 1a R = H b R = OMe O HO HO O O Me Me O H R Br i, 70.5 2 O O O Me Me O H R Br 3 iii 55 O O O O Me Me H H R H H iv 50ndash;60 ii 85ndash;90 4 2 3 5 6 9 10 11 Br O(1) O(2) O(3) O(4) A simple construction of chiral fused benzoxocine ring ethers from d-glucose by regioselective 8-endo-aryl radical cyclisation Partha Chattopadhyay,*a Monika Mukherjeeb and Soma Ghoshb a Indian Institute of Chemical Biology, Calcutta-700 032, India b Department of Solid State Physics, Indian Association for the Cultivation of Science, Jadavpur, Calcutta-700 032, India A regioselective 8-endo-trig aryl radical cyclisation of the 5,6-deoxy-D-xylo-5-enofuranosides 3a and 3b with trin- butyltin hydride provides the chiral furo3,2-c2benzoxocines 4a and 4b in good yields; the crystal structure of 4a is reported. The synthesis of condensed cyclic ethers incorporating medium size rings, a unique structural feature present in some highly bioactive marine natural products,1 is a challenging problem.The development of new and general methodology for the synthesis of this class of compound,2,3 especially in chiral form, has become an attractive area for investigation in recent years. The syntheses of chiral 5-, 6- and 7-membered cyclic ethers have been achieved from d-glucose by intramolecular nitrone cycloaddition reactions.4 More recently, functionalised 9-membered chiral ethers have been prepared from d-glucose through oxy-Cope rearrangement.5 We report herein a simple and convenient conversion of d-glucose to highly functionalised chiral condensed tricyclic benzoethers incorporating a cis 8-5 bicyclic system by regioselective 8-endo-trig aryl radical cyclisation.6 The transformation of the easily accessible 5,6-deoxy- O-isopropylidene-3-O-(o-bromobenzyl)-a-d-xylo-5-enofuranose 3a and the corresponding 5A-methoxy derivative 3b to the tricyclic furo3,2-c2benzoxocines 4a and 4b is shown in Scheme 1.d-Glucose was converted to the 3-O-(o-bromobenzyl) ethers 1adagger; and 1b through O-benzylation of 1,2 : 5,6-diisopropylidene-a-D-glucofuranose with 50 aq. NaOH in a biphasic medium (CH2Cl2ndash;H2O) using Bu4NBr as phase transfer catalyst. Under mild acidic condition, the 5,6-O-isopropylidene group in 1a,b was selectively deprotected to give 2a,b which on treatment with Ph3P, I2 and imidazole in boiling toluene7 gave the desired dideoxy furanose derivatives 3a and 3b.Radical cyclisation of each of the alkenes 3a and 3b in refluxing benzene (0.008 mol dm23) for 8ndash;10 h with Bu3SnH (1.5 equiv.) and a catalytic amount of AIBN furnished the respective crystalline tricyclic ethers 4a and 4b in 50ndash;60 yield as the only isolable products in each case after separation of the tin compounds8 followed by chromatography on silica gel. The assigned structures of the products 4a and 4b resulting from 8-endo-trig aryl radical cyclisation were based upon spectroscopic data.Unequivocal confirmation of the structure of 4a was obtained from an X-ray crystal structureDagger; determination (Fig. 1). In conclusion, the present investigation clearly shows the potential of regioselective aryl radical cyclisation from carbohydrate derived substrates in the synthesis of chiral condensed cyclic ethers incorporating medium sized rings. Grateful acknowledgement is due to Professor U. R. Ghatak, INSA Senior Scientist, for his kind interest and valuable suggestions.We also extend our thanks to the Regional Sophisticated Instruments Center, Bose Institute, Calcutta, India, for the use of its single crystal diffractometer facility. Footnotes and References * E-mail: iichbio@giasclo1.vsnl.net.in dagger; Satisfactory elemental analyses and spectroscopic data were obtained for all new compounds. Selected data for 4a mp 151ndash;152 deg;C; a27 D 220.6 (c 0.34, CHCl3); dH(CDCl3) 1.3 (s, 3 H), 1.46 (s, 3 H), 2.04ndash;2.28 (m, 2 H), 2.44ndash;2.68 (m, 1 H), 3.18ndash;3.44 (m, 1 H), 4.04 (d, 1 H, J 4, H-3a), 4.28 (dt, 1 H, J 6 and 4, H-11a), 4.58 (d, 1 H, J 14), 4.62 (d, 1 H, J 4, H-3), 5.1 (d, J 14, 1 H), 5.90 (d, 1 H, J 4, H-2), 7.02ndash;7.34 (m, 4 H, Ar-H); dC(CDCl3) 26.2, 27.7, 28.6, 31.0, 75.0, 79.0, 84.5, 85.4, 104.0, 111.1, 126.1, 128.3, 128.8, 130.5, 135.7, 140.6; MS (EI) m/z 276 (M+).For 4b: mp 106ndash;107 deg;C; a24 D + 2.6 (c 0.23, CHCl3); dH(CDCl3) 1.31 (s, 3 H), 1.46 (s, 3 H), Scheme 1 Reagents and conditions: Bu4NBr, 50 NaOH, CH2Cl2, 25 deg;C, 12 h; ii, 75 AcOH, 25 deg;C, 12 h; iii, PPh3, I2, imidazole, PhMe, reflux, 2 h; iv, Bu3SnH, AIBN, benzene, 200 W lamp, reflux, 10 h Fig. 1 ORTEP diagram of 4a Chem. Commun., 1997 21392.09ndash;2.21 (m, 2 H), 2.45ndash;2.57 (m, 1 H), 3.17ndash;3.31 (m, 1 H), 3.78 (s, 3 H, OMe), 4.02 (d, 1 H, J 4, H-3a), 4.22ndash;4.29 (dt, 1 H, J 6 and 4, H-11a), 4.56 (d, 1 H, J 14), 4.62 (d, 1 H, J 4, H-3), 5.05 (d, J 14, 1 H), 5.89 (1 H, d, J 4, H-2), 6.64 (d, 1 H, J 2.5), 6.76ndash;6.80 (1 H, dd, J 8 and 2.5), 7.08 (1 H, d, J 8); dC(CDCl3) 26.2, 26.7, 27.8, 31.3, 55.2, 74.9, 78.9, 84.2, 85.4, 103.9, 111.2, 113.3, 114.4, 131.6, 134.6, 136.8, 157.8; MS (EI) m/z 360 (M+).Dagger; Crystal data for 4a: C16H20O4, M = 276.33, orthorhombic, space group P212121, a = 8.6733(6), b = 9.1234(6), c = 17.9110(11) Aring;, U = 1417.3(2) Aring;3, Z = 4, Dc = 1.295 g cm23, m(Mo-Ka radiation, l = 0.71073 Aring;) = 0.86 cm21, 2qmax = 50deg;. 1412 reflections were recorded on an Enraf-Nonius CAD-4 diffractometer at 293 K.The structure was solved by direct method (MULTAN88) and refined by the full-matrix least-squares technique (SHELXL93). The function minimised was Sw(F0 2 2 Fc 2) w = 1/s2(F0 2) + (0.06P)2 where P = (F0 2 + 2Fc 2)/3. Anisotropic refinement of nonhydrogen atoms and isotropic refinement of hydrogen atoms, located from difference Fourier maps, converged at R1 = 0.0415 (wR2 = 0.0881) for 1069 reflections with, I 2s(I). Goodness of fit = 1.146 maximum/ minimum residual electron densities +0.204/20.244 e Aring;23.CCDC 182/616. 1 Y.-Y. Lin, M. Risk, S. M. Roy, D. van Engen, J. Clardy, J. Golik, J. C. James and K. Nakanishi, J. Am. Chem. Soc., 1981, 103, 6773; M. Murata, M. Kumagai, J. S. Lee and T. Yasumoto, Tetrahedron Lett., 1987, 28, 5869; H. Nagai, K. Torigoe, M. Satake, M. Murata, T. Yasumoto and H. Hirota, J. Am. Chem. Soc., 1992, 114, 1102; M. Satake, M. Murata and T. Yasumoto, Tetrahedron Lett., 1993, 34, 1975; M.Satake, M. Murata and T. Yasumoto, J. Am. Chem. Soc., 1993, 115, 361; M. Murata, H. Naoki, T. Iwashita, S. Matsunaga. M. Sasaki, A. Yokoyama and T. Yasumoto, J. Am. Chem. Soc., 1993, 115, 2060; T. Yasumoto and M. Murata, Chem. Rev., 1993, 93, 1897. 2 For the synthesis of 8-membered condensed ether ring systems, see J.-i. Yamada, T. Asano, I. Katoda and Y. Yamamoto, J. Org. Chem., 1990, 55, 6066; E. Alvarez, M.-L. Candenas, R. Perez, J. L. Ravelo and J. D. Martin, Chem.Rev., 1995, 95, 1953; K. C. Nicolaou, Angew. Chem., Int. Ed. Engl., 1996, 35, 589 and references cited therein; E. Alvarez, M. Delgado, M. T. Diaz, L. Hanxing, R. Perez and J. D. Martin, Tetrahedron Lett., 1996, 37, 2865; J. S. Clark and J. G. Kettle, Tetrahedron Lett., 1997, 38, 123 and 127. 3 For the synthesis of 9-membered ether ring systems, see M. Inoue, M. Sasaki and K. Tachibana, Tetrahedron Lett., 1997, 38, 1611 and references cited therein. 4 A. Bhattacharjya, P. Chattopadhyay, A. T. McPhail and D. R. McPhail, J. Chem. Soc., Chem. Commun., 1990, 1508; 1991, 136; P. M. Collins, M. S. Ashwood, H. Eder, S. H. B. Wright and D. J. Kennedy, Tetrahedron Lett., 1990, 31, 2055; S. Dutta, P. Chattopadhyay, R. Mukhopadhyay and A. Bhattacharjya, Tetrahedron Lett., 1993, 34, 3585; T. K. M. Shing, W.-C. Fung and C.-H. Wong, J. Chem. Soc., Chem. Commun., 1994, 449; A. Bhattacharjee, A. Bhattacharjya and A. Patra, Tetrahedron Lett., 1995, 35, 4677. 5 A. V. R. L. Sudha and M. Nagarajan, J. Chem. Soc., Chem. Commun., 1996, 1359 and references cited therein. 6 K. Ghosh, A. K. Ghosh and U. R. Ghatak, J. Chem. Soc., Chem. Commun., 1994, 629. 7 P. J. Garegg and B. Samuelsson, Synthesis, 1979, 469. 8 G. Stork and N. H. Baine, J. Am. Chem. Soc., 1982, 104, 2321. Received in Cambridge, UK, 27th August 1997; 7/06249D 2140 Chem. Commun., 1997