Asymmetric synthesis of phorboxazole B - Part II: Synthesis of the C1-C19 subunit and fragment assembly

Angewandte Chemie - International Edition

Volumn 39, Issue 14, 2000, Pages 2536-2540

  Evans, David A ^a   Fitch, Duke M ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

Aldol reactions; Antitumor agents; Macrolides; Natural products; Total synthesis

Indexed keywords

PHORBOXAZOLE B;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; MOLECULAR INTERACTION;

EID: 0034679493     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/1521-3773(20000717)39:14<2536::AID-ANIE2536>3.0.CO;2-U     Document Type: Article

References (35)

1. D. A. Evans, V. J. Cee, T. E. Smith, D. M. Fitch, P. S. Cho, Angew. Chem. 2000, 112, 2633-2636; Angew. Chem. Int. Ed. 2000, 39, 2533- 2536.
2. D. A. Evans, V. J. Cee, T. E. Smith, D. M. Fitch, P. S. Cho, Angew. Chem. 2000, 112, 2633-2636; Angew. Chem. Int. Ed. 2000, 39, 2533-2536.
3. Abbreviations: Ac = acetyl; Ms = methanesulfonyl; TIPS = tiisopropylsilyl: TES = triethylsilyl; TMS = trimethylsilyl; DIBAlH = diisobutylaluminum hydride; Tf = trifluoromethanesulfonyl; Bn = benzyl; DMAP = 4-dimethylaminopyridine; pyr = pyridine; tol = toluene; TBAF = tetra-n-butylammonium fluoride; DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene; lut = 2,6-lutidine; Boc = tert-butyloxycarbonyl.
4. D. A. Evans, M. C. Kozlowski, J. A. Murry, C. S. Burgey, K. R. Campos, B. T. Connell, R. J. Staples, J. Am. Chem. Soc. 1999, 121, 669-685.
5. T. H. Chan, M. A. Brook, T. Chaly, Synthesis 1983, 203-205.
6. 1H NMR analysis (500 MHz) of the unpurified reaction mixture.
7. Although the anomers were separable by chromatography on silica gel, the mixture was generally taken on without purification.
8. 4 led to high levels of decomposition.
9. For an early example of nucleophilic addition to oxocarbenium ions in the synthesis of C-glycosides, see M. D. Lewis, J. K. Cha, Y. Kishi, J. Am. Chem. Soc. 1982, 104, 4976-4978.
10. r = 13 min).
11. E. L. Eliel, S. H. Wilen, L. N. Mander, Stereochemistry of Organic Compounds, Wiley, New York, 1994, chap. 11.
12. 2, -91 C, 95% yield) of the known ethyl ester. See J. S. Panek, R. T. Beresis, J. Org. Chem. 1996, 61, 6496-6497.
13. Dr. David MacMillan is gratefully acknowledged for the development of this reaction.
14. r = 36.8 min).
15. D. A. Evans, D. W. C. MacMillan, K. R. Campos, J. Am. Chem. Soc. 1997, 119, 10859-10860.
16. Dihydroxylation was performed using the achiral ligand, quinuclidine. For a review of asymmetric dihydroxylation under these conditions, see H. C. Kolb, M. S. VanNieuwenhze, K. B. Sharpless, Chem. Rev. 1994, 94, 2483-2547.
17. D. A. Evans, B. W. Trotter, P. J. Coleman, B. Côté, L. C. Dias, H. A. Rajapakse, A. N. Tyler, Tetrahedron 1999, 55, 8671-8726.
18. D. A. Evans, P. J. Coleman, B. Côté, J. Org. Chem. 1997, 62, 788-789. See also I. Paterson, K. R. Gibson, R. M. Oballa, Tetrahedron Lett. 1996, 37, 8585-8588.
19. D. A. Evans, P. J. Coleman, B. Côté, J. Org. Chem. 1997, 62, 788-789. See also I. Paterson, K. R. Gibson, R. M. Oballa, Tetrahedron Lett. 1996, 37, 8585-8588.
20. 1H NMR analysis (500 MHz) of the unpurified reaction mixture. The relative stereochemistry of this product was determined by X-ray crystallography.
21. The remainder of the material was comprised of cleanly recovered 3 and 4.
22. Hemiketal 2 existed as a 92:8 mixture of the closed hemiketal and open hydroxy ketone. This mixture was taken on together in the subsequent reduction.
23. K. S. Kim, Y. H. Song, B. H. Lee, C. S. Hahn, J. Org. Chem. 1986, 51, 404-407.
24. The lithium anions of methyl and ethyl propiolate failed to alkylate a model primary trifluoromethanesulfonate derived from the commercial available tetrahydropyran-2-methanol at low temperature (-78°C) and decomposed upon warming, see M. M. Midland, A. Tramontano, J. R. Cable, J. Org. Chem. 1980, 45, 28-29. Displacement of this model trifluoromethanesulfonate with the dianion of propiolic acid was complicated by O alkylation and double alkylation, which was surpressed through use of the alternative nucleophile 15. For a complex example of the use of an N-phenylamide as a carboxyl surrogate with attenuated nucleophilicity, see D. A. Evans, P. H. Carter, E. M. Carreira, A. B. Charette, J. A. Prunet, M. Lautens, J. Am. Chem. Soc. 1999, 121, 7540-7552. For the synthesis of 15, see G. M. Coppola, R. E. Damon, Synth. Commun. 1993, 23, 2003-2010. For the alkylation of carbonyl compounds with the dianion of N- benzylpropynamide, see G. M. Coppola, R. E. Damon, J. Heterocycl. Chem. 1995, 32, 1133-1139.
25. The lithium anions of methyl and ethyl propiolate failed to alkylate a model primary trifluoromethanesulfonate derived from the commercial available tetrahydropyran-2-methanol at low temperature (-78°C) and decomposed upon warming, see M. M. Midland, A. Tramontano, J. R. Cable, J. Org. Chem. 1980, 45, 28-29. Displacement of this model trifluoromethanesulfonate with the dianion of propiolic acid was complicated by O alkylation and double alkylation, which was surpressed through use of the alternative nucleophile 15. For a complex example of the use of an N-phenylamide as a carboxyl surrogate with attenuated nucleophilicity, see D. A. Evans, P. H. Carter, E. M. Carreira, A. B. Charette, J. A. Prunet, M. Lautens, J. Am. Chem. Soc. 1999, 121, 7540-7552. For the synthesis of 15, see G. M. Coppola, R. E. Damon, Synth. Commun. 1993, 23, 2003-2010. For the alkylation of carbonyl compounds with the dianion of N- benzylpropynamide, see G. M. Coppola, R. E. Damon, J. Heterocycl. Chem. 1995, 32, 1133-1139.
26. The lithium anions of methyl and ethyl propiolate failed to alkylate a model primary trifluoromethanesulfonate derived from the commercial available tetrahydropyran-2-methanol at low temperature (-78°C) and decomposed upon warming, see M. M. Midland, A. Tramontano, J. R. Cable, J. Org. Chem. 1980, 45, 28-29. Displacement of this model trifluoromethanesulfonate with the dianion of propiolic acid was complicated by O alkylation and double alkylation, which was surpressed through use of the alternative nucleophile 15. For a complex example of the use of an N-phenylamide as a carboxyl surrogate with attenuated nucleophilicity, see D. A. Evans, P. H. Carter, E. M. Carreira, A. B. Charette, J. A. Prunet, M. Lautens, J. Am. Chem. Soc. 1999, 121, 7540-7552. For the synthesis of 15, see G. M. Coppola, R. E. Damon, Synth. Commun. 1993, 23, 2003-2010. For the alkylation of carbonyl compounds with the dianion of N- benzylpropynamide, see G. M. Coppola, R. E. Damon, J. Heterocycl. Chem. 1995, 32, 1133-1139.
27. The lithium anions of methyl and ethyl propiolate failed to alkylate a model primary trifluoromethanesulfonate derived from the commercial available tetrahydropyran-2-methanol at low temperature (-78°C) and decomposed upon warming, see M. M. Midland, A. Tramontano, J. R. Cable, J. Org. Chem. 1980, 45, 28-29. Displacement of this model trifluoromethanesulfonate with the dianion of propiolic acid was complicated by O alkylation and double alkylation, which was surpressed through use of the alternative nucleophile 15. For a complex example of the use of an N-phenylamide as a carboxyl surrogate with attenuated nucleophilicity, see D. A. Evans, P. H. Carter, E. M. Carreira, A. B. Charette, J. A. Prunet, M. Lautens, J. Am. Chem. Soc. 1999, 121, 7540-7552. For the synthesis of 15, see G. M. Coppola, R. E. Damon, Synth. Commun. 1993, 23, 2003-2010. For the alkylation of carbonyl compounds with the dianion of N-benzylpropynamide, see G. M. Coppola, R. E. Damon, J. Heterocycl. Chem. 1995, 32, 1133-1139.
28. Similar conditions have recently appeared in the literature for an oxazole-stablized Wittig coupling, see P. Liu, J. S. Panek, J. Am. Chem. Soc. 2000, 122, 1235-1236.
29. For the hydrolysis of the N-Boc derivatives of secondary amides and lactams with LiOH, see D. L. Flynn, R. E. Zelle, P. A. Grieco, J. Org. Chem. 1983, 48, 2424-2426.
30. J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi, Bull. Chem. Soc. Jpn. 1979, 52, 1989-1993.
31. 1H NMR and 2D COSY experiments.
32. The difference in the selectivity between the two bases is perhaps a result of the formation of a more active silylaling agent derived from the reaction of imidazole with the silyl chloride. Presumably there is no reaction between the silyl chloride and 2,6-lutidine, which simply acts as a base.
33. The use of 1-hexene as a co-solvent was found to effectively surpress any overreduction. For related conditions, see T.-L. Ho, S.-H. Liu, Synth. Commun. 1987, 17, 969-973.
34. J. R. Parikh, W. von E. Doering, J. Am. Chem. Soc. 1967, 89, 5505-5507.
35. 1H NMR spectra of natural phorboxazole B for comparison.