Concise asymmetric routes to 2,2,4-trisubstituted tetrahydrofurans via chiral titanium imide enolates: Key intermediates towards synthesis of highly active azole antifungals Sch 51048 and Sch 56592

Tetrahedron Letters

Volumn 37, Issue 32, 1996, Pages 5657-5660

  Saksena, Anil K ^a   Girijavallabhan, Viyyoor M ^a   Wang, Haiyan ^a   Liu, Yi Tsung ^a   Pike, Russell E ^a   Ganguly, Ashit K ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIFUNGAL AGENT; POSACONAZOLE; SCH 51048; TETRAHYDROFURAN DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0030570911     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01203-8     Document Type: Article

References (21)

1. 1. (a) A. K. Saksena, V. M. Girijavallabhan, R. G. Lovey, F. Bennett, R. E. Pike, H. Wang, P. Pinto, Y.T. Liu, N. Patel and A. K. Ganguly, 35th Interscience Conference on Antimicrobial Agents and Chemotherapy ( ICAAC ), San Francisco, 17-20 September 1995 (abstract nos. F 61 and F 83);
2. (b) A. K. Saksena, V. M. Girijavallabhan, R. G. Lovey, R. E. Pike, J. A. Desai, A. K. Ganguly, R. S. Hare, D. Loebenberg, A. Cacciapouti and R. M. Parmegiani, Bioorg. Med. Chem. Lett., 1995, 5, 2023; Sch 56592: (-)-4-[4-[4-[ [ (R-cis)-5-(2,4-diflurophenyl)-tetrahydro-5-(1H-1,2,4-triazol-1-ylmethyl) -3-furanyl] methoxy]phenyl]-1-piperazinyl] phenyl]-2,4-dihydro-2-[ (S)-1-ethyl-2(S)-hydroxypropyl]-3H-1,2,4-triazol-3-one.
3. 2. A. K. Saksena, V. M. Girijavallabhan, R. G. Lovey, R. E. Pike, H. Wang, A. K. Ganguly, B. Morgan, A. Zaks and M.S. Puar, Tetrahedron Lett. 1995, 36, 1787.
4. 3. Review: D. A. Evans, Aldrichimica Acta, 1994, 15, 23; and cited references.
5. 4. W. Oppolzer, J. Blagg, I. Rodrigues and E. Walther, J. Am. Chem. Soc. 1990, 112, 2767; and cited references.
6. 5. D. A. Evans, M.D. Ennis and D.J. Mathre, J. Am. Chem. Soc. 1982, 104, 1737.
7. 6. A. K. Saksena, V. M. Girijavallabhan, R. G. Lovey, R. E. Pike, J. A. Desai, A. K. Ganguly, R. S. Hare, D. Loebenberg, A. Cacciapouti and R. M. Parmegiani, Bioorg. Med. Chem. Lett., 1994, 4, 2023.
8. 7. W. S. Johnson, L. Werthmann, W. R. Bartlett, T. T. Brocksom, Tsung-tee Li, D. J. Faulkner, M. R. Peterson, J. Am. Chem. Soc. 1990, 112, 8215.
9. 8. Yields refer to isolated products and have not been optimised. All new compounds were characterised by PMR, CMR and high resolution mass spectra. When necessary diff NOE, COSY and NOESY spectra were obtained. Cis:trans ratios of iodocyclization products were determined by NMR as fully described in ref. 2. Where applicable, optical purity of key intermediates was determined by chiral shift NMR spectroscopy. Chiralcel® OD Analytical Columns (Chiral Technologies Inc.) were also used to determine optical purity of a number of final compounds. Selected spectral data is given here.
10. 3] δ 0.90 (dd, J = 6.7 Hz, 18.0 Hz, 6H), 2.30 -2.43 ( m, 1H), 2.74 - 2.90 ( m, 2H), 2.95 - 3.20 ( m, 2H ), 4.15 - 4.30 ( m, 2H), 4.40 - 4.47 ( m, 1H), 5.20 ( s, 1H), 5.30 (s, 1H), 6.77 - 6.92 (m, 2H), 7.20 - 7.30 (m, 1H).
11. 3] δ 0.75 (dd, J = 5.3 Hz, 33.8 Hz, 6H), 2.19 - 2.30 (m, 1H), 2.62 (dd, J = 6.0 Hz, 15.0 Hz, 1H), 2.91 (dd, J = 7.5 Hz, 12.8 Hz, 1H), 3.60 (dd, J = 6.0 Hz, 10.5 Hz, 1H ), 3.66 (t, J = 7.5 Hz, 1H), 4.12 ( m, 2H), 4.31 ( m, 2H); 4.43 ( dd, J = 12.0 Hz, 18.8 Hz, 2 H), 5.10 ( S, 1H); 5.23 ( S, 1H), 6.70 - 6.85 ( m, 2H), 7.09 - 7.34 ( m, 6H).
12. 11. M. Nerz-Stormes and E.R. Thornton, Tetrahedron Lett. 1986, 27, 897; J. Org. Chem. 1991, 56, 2489.
13. 11. M. Nerz-Stormes and E.R. Thornton, Tetrahedron Lett. 1986, 27, 897; J. Org. Chem. 1991, 56, 2489.
14. 12. D.A. Evans, F. Urpi, T.C. Somers, J.S. Clark, M.T. Bilodeau, J. Am. Chem. Soc. 1990, 112, 8215.
15. 2O), 2.50 (d, J = 7.5 Hz, 2H), 3.45 (dd, J = 6.8 Hz, 9.0 Hz, 1H), 3.52 - 3.75 (m, 3H), 4.46 (dd, J = 7.5 Hz, 13.5 Hz, 2H); 5.17 (s, 1H), 5.23 (s, 1H), 6.73 - 6.86 (m, 2H), 7.12 - 7.38 ( m, 6H).
16. 3 )..
17. 15. S. D. Rychnovsky and P. A. Bartlett, J. Am. Chem. Soc. 1981, 103, 3963.
18. 3] δ 2.64 - 3.01 (m, 3H), 3.24 (dd, J = 3.4 Hz, 13.5 Hz, 1H), 3.77 - 3.91 (bs, 2H), 4.0 - 4.18 (m, 3H), 4.49 - 4.61 (m, 1H), 5.19 (s, 1H), 5.33 (s, 1H); 6.73 - 7.4 (m, 8H).
19. 3] δ 2.61 - 2.95 ( m, 3H), 3.28 ( dd, J = 3.4 Hz, 13.3 Hz, 1H), 3.79 ( AB quartet, J = 16.7 Hz, 2H), 4.05 - 4.33 ( m, 5H), 4.65 - 4.76 ( m, 1H), 6.75 - 7.61 ( m, 8H).
20. 2
21. 19. 35th Interscience Conference on Antimicrobial Agents and Chemotherapy ( ICAAC ), San Francisco, 17-20 September1995 (abstract nos. F 61, F 62, F63, F 64, F 65, F 66, F 67, F 68, and F 83).