A Route to the Tetrahydrofuran Segment of Amphidinolides X and Y, and Its Quaternary-Carbon Epimer

Abstract

A short approach to the tetrahydrofuran fragment of amphidinolides X and Y has been developed through the combination of iterative Sharpless asymmetric epoxidations, Pd-catalyzed regio­selective hydrogenolysis of a 4,5-epoxy-2-alkenoate and the disfavored 5-endo-tet ring closure of a β-hydroxy epoxide promoted by a double bond adjacent to the epoxide function.

amphidinolides - cyclization - palladium - stereoselective synthesis

References and Notes

1a Kobayashi J. Tsuda M. Nat. Prod. Rep.  2004,  21:  77 

1b Kobayashi J. Ishibashi M. In Comprehensive Natural Products Chemistry   Vol. 8:  Mori K. Elsevier; Amsterdam: 1999.  p.415 

2 Tsuda M. Izui N. Shimbo K. Sato M. Fukushi E. Kawabata J. Katsumata K. Horiguchi T. Kobayashi J. J. Org. Chem.  2003,  68:  5339 

3 For a review on the synthesis of macrodiolide natural products, see: Kang EJ. Lee E. Chem. Rev.  2005,  105:  4348 

4 Tsuda M. Izui N. Shimbo K. Sato M. Fukushi E. Kawabata J. Kobayashi J. J. Org. Chem.  2003,  68:  9109 

5a Lepage O. Kattnig E. Fürstner A. J. Am. Chem. Soc.  2004,  126:  15970 

5b Fürstner A. Kattnig E. Lepage O. J. Am. Chem. Soc.  2006,  128:  9194 

6a Narayan RS. Sivakumar M. Bouhlel E. Borhan B. Org. Lett.  2001,  3:  2489 

6b Narayan RS. Borhan B. J. Org. Chem.  2006,  71:  1416 

Nicolaou and co-workers pioneered in the study of regioselective hydroxy epoxide openings controlled by a double bond. See:

7a Nicolaou KC. Prasad CVC. Somers PK. Hwang C.-K. J. Am. Chem. Soc.  1989,  111:  5330 

7b Nicolaou KC. Prasad CVC. Somers PK. Hwang C.-K. J. Am. Chem. Soc.  1989,  111:  5335 

8 Chen Y. Jin J. Wu J. Dai W.-M. Synlett  2006,  1177 

9 Oshima M. Yamazaki H. Shimizu I. Nisar M. Tsuji J. J. Am. Chem. Soc.  1989,  111:  6280 

For recent examples of the use of this methodology in synthesis, see:

10a Noguchi Y. Yamada T. Uchiro H. Kobayashi S. Tetrahedron Lett.  2000,  41:  7499 

10b Tholander J. Carreira EM. Helv. Chim. Acta  2001,  84:  613 

11a Mori K. Tetrahedron  1977,  33:  289 

11b Tago K. Arai M. Kogen H. J. Chem. Soc., Perkin Trans. 1  2000,  2073 

12

Physical data for 7: liquid; [α]_D ²⁰ +8.5 (c = 2, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.89 (t, J = 7.0 Hz, 3 H), 1.25 (s, 3 H), 1.29-1.62 (m, 4 H), 2.84 (dd, J = 4.8, 6.8 Hz, 1 H), 2.94 (q, J = 4.2, 6.7 Hz, 1 H), 3.64 (ddd, J = 4.7, 7.1, 12.2 Hz, 1 H), 3.80 (ddd, J = 4.2, 7.4, 12.2 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.0, 16.7, 18.3, 40.6, 61.4 (2 × C), 63.2. Anal. Calcd for C₇H₁₄O₂: C, 64.58; H, 10.84; O, 24.58. Found: C, 64.53; H, 10.77; O, 24.21.

13

Enantiomeric excess was determined by ¹H NMR analysis (C₆D₆, 300 MHz) of the corresponding acetate of 7, in the presence of the chiral shift reagent Eu(hfc)₃.

14 Vatèle J.-M. Tetrahedron Lett.  2006,  47:  715 

15

Physical data for 5: oil; [α]_D ²⁰ -12 (c = 1, CHCl₃). ¹ NMR (300 MHz, CDCl₃): δ = 0.91 (t, J = 7.0 Hz, 3 H), 1.24 (s, 3 H), 1.27 (t, J = 7.1 Hz, 3 H), 1.35-1.66 (m, 4 H), 3.29 (dd, J = 0.9, 6.4 Hz, 1 H), 4.18 (q, J = 7.1 Hz, 2 H), 6.07 (dd, J = 0.9, 15.7 Hz, 1 H), 6.81 (dd, J = 6.5, 15.7 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.0, 14.2, 16.5, 18.4, 40.5, 60.6, 61.3, 64.2, 124.8, 143.0, 165.7. Anal. Calcd for C₁₁H₁₈O₃: C, 66.64; H, 9.15; O, 24.24. Found: C, 66.60; H, 9.38; O, 24.01.

16

A small amount of its corresponding Z-isomer was also isolated (5%).

17

Physical data for 8: oil; [α]_D ²⁰ -3.0 (c = 2, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.89 (t, J = 6.8 Hz, 3 H), 1.16 (s, 3 H), 1.26 (t, J = 7.1 Hz, 3 H), 1.33-1.46 (m, 4 H), 1.91 (s, 1 H), 2.32 (dd, J = 1.0, 7.8 Hz, 2 H), 4.15 (q, J = 7.1 Hz, 2 H), 5.83 (dt, J = 1.2, 15.6 Hz, 1 H), 6.97 (quint, J = 7.8, 15.6 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.2, 14.5, 17.0, 27.0, 44.4, 44.8, 60.3, 72.5, 124.2, 144.9, 166.4. Anal. Calcd for C₁₁H₂₀O₃: C, 65.97; H, 10.07; O, 23.97. Found: C, 65.72; H, 10.22; O, 24.05.

18 Evans DA. Bender SL. Morris J. J. Am. Chem. Soc.  1988,  110:  2506 

19

Low diastereoselectivity was observed when the epoxidation was conducted with MCPBA (20% de).

For examples of the influence of alcohol functions on the diastereoselectivity of the Sharpless epoxidation, see:

20a Takano S. Setoh M. Takahashi M. Ogasawara K. Tetrahedron Lett.  1992,  33:  5365 

20b Rizzi JP. Kende AS. Tetrahedron  1984,  22:  4693 

20c Naruta Y. Nishigaichi Y. Maruyama K. Tetrahedron Lett.  1989,  30:  3319 

21 De Mico A. Margarita R. Parlanti L. Vescovi A. Piancatelli G. J. Org. Chem.  1997,  62:  6974 

22

Analytical data for 3: oil; [α]_D ²⁰ -20.1 (c = 1.2, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.90 (t, J = 7.0 Hz, 3 H), 1.32 (s, 3 H), 1.20-1.50 (m, 4 H), 1.71 (dd, J = 6.4, 12.8 Hz, 1 H), 2.16 (dd, J = 7.4, 12.8 Hz, 1 H), 2.36 (br s, 1 H), 4.02 (q, J = 6.4 Hz, 1 H), 4.13 (t, J = 6.4 Hz, 1 H), 5.18 (dd, J = 0.9, 10.3 Hz, 1 H), 5.34 (dt, J = 1.3, 17.1 Hz, 1 H), 5.83 (ddd, J = 6.7, 10.3, 17.1 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.6, 17.8, 27.2, 45.1 (2 × C), 76.8, 82.6, 85.3, 117.1, 137.2. Anal. Calcd for C₁₀H₁₈O₂: C, 70.55; H, 10.66; O, 18.8. Found: C, 70.35; H, 10.82; O, 18.82. Analytical data for 11: oil; [α]_D ²⁰ -16.3 (c = 1, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 0.92 (t, J = 7.0 Hz, 3 H), 1.21 (s, 3 H), 1.35 (m, 2 H), 1.57 (m, 2 H), 1.84 (dd, J = 7.1, 12.5 Hz, 1 H), 2.05 (dd, J = 6.7, 12.5 Hz, 1 H), 2.28 (br s, 1 H), 4.04 (m, 2 H), 5.19 (dt, J = 0.9, 10.2 Hz, 1 H), 5.34 (dt, J = 0.8, 17.2 Hz, 1 H), 5.84 (ddd, J = 6.7, 10.2, 17.2 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 14.7, 17.9, 27.8, 44.4, 45.2, 76.4, 82.4, 85.7, 117.4, 137.6. Anal. Calcd for C₁₀H₁₈O₂: C, 70.55; H, 10.66; O, 18.8. Found: C, 70.77; H, 10.52; O, 18.69.

23a Brown HC. Cope OJ. J. Am. Chem. Soc.  1964,  86:  1801 

23b Brown HC. Chen JC. J. Org. Chem.  1981,  46:  3978 

24

[α]_D ²⁰ -43.7 (c = 1.6, CHCl₃); lit.⁵ [α]_D ²⁰ -37.1 (c = 1, CHCl₃, 83% ee); lit.⁸ [α]_D ²⁰ -52.2 (c = 0.8, CHCl₃, >96% ee).

25

[α]_D ²⁰ -45.3 (c = 1.8, CHCl₃); lit.⁵ [α]_D ²⁰ -43.5 (c = 0.97, CHCl₃, 83% ee).