Synthesis of (tetrahydrofuranyl)tetrahydrofurans via radical cyclization of bis(β-alkoxyacrylates)

Abstract

Radical cyclizations of bis(β-alkoxyacrylates) obtained from (3R,4R)- and meso-1,6-dibromohexane-3,4-diol proceed to form a C₂-symmetric and a meso (tetrahydrofuranyl)tetrahydrofuran derivative.

References

1. (a) E. Lee, J. S. Tae, C. Lee and C. M. Park, Tetrahedron Lett., 1993, 34, 4831; (b) E. Lee, J. S. Tae, Y. H. Chong, Y. C. Park, M. Yun and S. Kim, Tetrahedron Lett., 1994, 35, 129; (c) E. Lee and C. M. Park, J. Chem. Soc., Chem. Commun., 1994, 293; (d) E. Lee, J.-w. Jeong and Y. Yu, Tetrahedron Lett., 1997, 38, 7765; (e) E. Lee, C. M. Park and J. S. Yun, J. Am. Chem. Soc., 1995, 117, 8017; (f) E. Lee, S.-K. Yoo, Y.-S. Cho, H.-S. Cheon and Y. H. Chong, Tetrahedron Lett., 1997, 38, 7757.
2. In this case, a small amount of the minor product 4 was also obtained.
3. E. Lee, S.-K. Yoo, H. Choo and H. Y. Song, Tetrahedron Lett., 1998, 39, 317.
4. ¹H-NMR (300 MHz, CDCl₃)δ 1.28 (d, 3H, J= 6.5 Hz), 1.90–1.95 (m, 1H), 2.17–2.19 (dd, 1H, J= 5.4, 1.6 Hz), 2.55 and 2.68 (AB of ABX, J_AB= 15.6 Hz, J_AX= 6.7 Hz, J_BX= 6.1 Hz), 3.70 (s, 6H), 4.06–4.09 (m, 1H), 4.40 (m, 1H), 4.50 (m, 1H), 5.17 (d, 1H, J= 12.7 Hz), 7.51 (d, 1H, J= 12.7 Hz); ¹³C-NMR (75 MHz, CDCl₃)δ 19.69, 37.54, 39.98, 51.18, 51.78, 74.33, 79.83, 86.18, 97.81, 160.70, 167.87, 171.06; MS (EI, relative intensity) 258 (M⁺, 3), 157 (86), 83 (100).
5. ¹H-NMR (300 MHz, CDCl₃)δ 1.56–1.66 (m, 2H), 1.73–1.83 (m, 2H), 1.91–2.11 (m, 4H), 2.47 and 2.61 (AB of ABX, J_AB= 15.2 Hz, J_AX= 6.9 Hz, J_BX= 6.4 Hz), 3.68 (s, 6H), 3.80–3.86 (m, 2H), 4.24–4.33 (m, 2H); ¹³C-NMR (75 MHz, CDCl₃)δ 27.59, 30.79, 40.68, 51.55, 75.70, 81.34, 171.63; MS (CI, relative intensity) 287 (M+1, 100), 255 (26), 213 (20); HRMS (CI) calcd for C₁₄H₂₃O₆ 287.1495, found 287.1493.
6. A trace amount of a minor (presumably epimeric) product was obtained.
7. Sharpless asymmetric dihydroxylation of trans-1,6-dibromohex-3-ene, obtained from trans-hex-3-ene-1,6-diol via mesylation and bromide substitution, provided 74% yield of (3R,4R)-1,6-dibromohexane-3,4-diol in high enantiomeric excess (>98%). Reaction of this diol with ethyl propiolate was a little sluggish, and gave 40% yield of the corresponding bis(β-alkoxyacrylate). Radical cyclization produced ethyl ester analogues of 16 and 17 in 72% and 6% yield, respectively.
8. [a]²⁸_D–8.9 (c 1.8, CHCl₃); ¹H-NMR (300 MHz, CDCl₃)δ 1.56–1.78 (m, 4H), 1.86–1.96 (m, 2H), 2.01–2.12 (m, 2H), 2.47 and 2.73 (AB of ABX, J_AB= 15.4 Hz, J_AX= 6.3 Hz, J_BX= 7.2 Hz), 3.68 (s, 6H), 3.80–3.87 (m, 2H), 4.25–4.34 (m, 2H); ¹³C-NMR (75 MHz, CDCl₃)δ 27.59, 30.94, 40.48, 51.50, 75.78, 81.55, 171.68; MS (CI, relative intensity) 287 (M + 1, 100), 255 (86), 213 (21); HRMS (CI) calcd for C₁₄H₂₃O₆ 287.1495, found 287.1499.
9. [a]²⁶_D–14.9 (c 0.62, CHCl₃); ¹H-NMR (300 MHz, CDCl₃)δ 1.32–1.44 (m, 2H), 1.54–1.71 (m, 4H), 1.84–1.94 (m, 2H), 2.41 and 2.58 (AB of ABX, J_AB= 15.3 Hz, J_AX= 7.3 Hz, J_BX= 5.7 Hz), 3.39 (br, 2H), 3.71 (s, 6H), 3.74–3.85 (m, 2H); ¹³C-NMR (75 MHz, CDCl₃)δ 25.69, 29.17, 41.29, 51.56, 71.34, 73.82, 171.97; MS (CI, relative intensity) 287 (M + 1, 77), 255 (100), 213 (34); HRMS (CI) calcd for C₁₄H₂₃O₆ 287.1495, found 287.1491.
10. (a) U. Koert, Synthesis, 1995, 115; (b) Many of the more recent references on the synthesis of Annonaceous acetogenins may be found in A. Sinha, S. C. Sinha, S. C. Sinha and E. Keinan, J. Org. Chem., 1999, 64, 2381.