New Routes to Functionalized Benzazepine Substructures: A Novel Transformation of an α-Diketone Thioamide Induced by Trimethyl Phosphite

Journal of Organic Chemistry

Volumn 55, Issue 3, 1990, Pages 831-838

  Fang, Francis G ^a   Maier, Martin E ^a   Danishefsky, Samuel J ^a   Schulte, Gayle ^a  

^a YALE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CEPHALOTAXINE; DIHYDROISOQUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; DRUG STRUCTURE; DRUG SYNTHESIS; METHODOLOGY; NONHUMAN;

EID: 0025303985     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/jo00290a011     Document Type: Article

References (33)

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2. Present address: Falkultat für Chemie, Universitat Konstanz, Postfach 5560 D-7750, Konstanz 1, Konstanz, West Germany.
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9. For previous synthesis of cephalotaxine (3) see:Auerbach, J.; Weinreb, S. M. J. Am. Chem. Soc. 1972, 94, 7172.
10. Semmelhack, M. F.; Chong, B. C.; Jones, L. D. J. Am. Chem. Soc. 1972, 94, 8629.
11. Weinreb, S. M.; Semmelhack, M. F. Acc. Chem. Res. 1975, 8, 158.
12. Yasuda, S.; Yamada, T.; Hanaoka, M. Tetrahedron Lett. 1986, 2023.
13. Kuehne, M. E.; Bornmann, W. G.; Parsons, W. H.; Spitzer, T. D.; Blount, J. F.; Zubieta, J. J. Org. Chem. 1988, 53, 3439.
14. Burkholder, T. P.; Fuchs, P. L. J. Am. Chem. Soc. 1988, 110, 2341.
15. Compound C (R = H, X = H2) served as a key intermediate in Weinreb's total synthesis of cephalotaxine (3) (see ref 5a) and has also been prepared by several other groups:Dolby, L. J.; Nelson, S. J.; Senkovich, D. J. Org. Chem. 1972, 37, 3691.
16. Weinstein, B.; Craig, A. R. J. Org. Chem. 1976, 41, 875.
17. Tse, I.; Snieckus, V. Chem. Commun. 1976, 505.
18. Slemon, C. E.; Hellwig, L. C.; Ruder, J.-P.; Hoskins, E. W.; McLean, D. B. Can. J. Chem. 1981, 59, 3055.
19. For a review on the use of Lawesson's reagent for the generation for the generation of thiocarbonyl compounds, see: Cava, M.; Levinson, M. I. Tetrahedron 1985, 41, 5061.
20. For a previous example of this type of cvclization see ref 2.
21. Tungsten hexacarbonyl has previously been utilized to reductively dimerize aryl dithiolanes: Yeung, L. L.; Luh, T.-Y. J. Chem. Soc., Chem. Commun. 1987, 981.
22. For examples of aryl-substituted tungsten carbonyl carbene complexes, see:Casey, C. P.; Burkhardt, T. J. J. Am. Chem. Soc. 1973, 95, 5833.
23. Casey, C. P.; Burkhardt, T. J. Bunnell, C. A.; Calabrese, J. C. J. Am. Chem. Soc. 1977, 99, 2127.
24. Muxfeldt, H.; Unterweger, W.-D.; Helmchen, G. Synthesis 1976, 694.
25. Muller, R. K.; Joos, R.; Felix, D.; Schreiber, J.; Wintner, C.; Eschenmoser, A. Org. Synth. 1976, 55, 114.
26. Lambert, J. B.; Huseland, D. E.; Wang, G.-T. Synthesis 1986, 657.
27. Westling, M.; Smith, R.; Livinghouse, T. J. Org. Chem. 1986, 51 (8), 1159.
28. Reaction of 41 with tosylhydrazide in ethanol in the presence of a catalytic amount of HC1 produced a single tosylhydrazine (1H NMR (250 MHz, CDCl3) ϑ 8.64 (broad s), 7.67 and 7.31 (ABq, JAB = 8.2 Hz, Δv = 92.1 Hz, 4 H, SO2ArH), 6.87 (s, 1 H, ArH), 6.56 (s, 1 H, ArH), 6.07 (s, 2 H, OCH2O), 3.85 (t, J = 7.8 Hz, 2 H, NCH2CH2Ar), 3.53 (t, J = 7.8 Hz, 2 H, NCH2CH2CH2), 3.00 (t, J = 7.5 Hz, 2 H, CSCH2), 2.88 (t, J = 7.8 Hz, 2 H, ArCH2), 2.55 (q, J = 8.2 Hz, 2 H, CH2CH3), 2.46 (s, 3 H, ArCH3), 1.98 (apparent p, J = 7.8 Hz, 2 H, CH2CH2CH2), 1.07 (t, J = 8.2 Hz, 3 H, CH2CH3)). Indirectly, this was shown to be the undesired regioisomer by its conversion to diazo ketone (II) (1H NMR (250 MHz, CDC13) ξ 6.87 (s, 1 H, ArH), 6.78 (s, 1 H, ArH), 6.00 (s, 2 H, OCH20), 3.93 (t, J = 7.8 Hz, 2 H, NCH2CH2Ar), 3.57 (t, J = 7.8 Hz, 2 H, NCH2CH2CH2), 3.02 (t, J = 7.7 Hz, 2 H, CSCH2), 2.96 (t, J = 7.8 Hz, 2 H, ArCH2), 2.52 (broad q, J = 7.8 Hz, 2 H, CH2CH3), 2.00 (apparent p, J = 7.8 Hz, 2 H, CH2CH2CH2), 1.20 (t, J = 7.8 Hz, 3 H, CH2CH3)) and subsequent rhodium(II) acetate dimer catalyzed decomposition to give enone III as a 2.5:1 mixture of olefin isomers (major isomer: 1H NMR (250 MHz, CDCl3) ℑ 7.12 (s, 1 H, ArH), 6.90 (s, 1 H, ArH), 6.58-6.30 (m, 2 H, HC=CH), 6.02 (s, 2 H, OCH20), 4.00 (t, J = 7.9 Hz, 2 H, NCH2CH2Ar), 3.73 (t, J = 7.7 Hz, 2 H, ArCH2), 3.04 (t, J = 7.5 Hz, 2 H, CSCH2), 2.08 (dd, J = 6.4 Hz and 1 Hz, 3 H, CH3), 2.00 (hidden p, 2 H, CH2CH2CH2)).
29. For the use of trimethyl phosphite to effect reductive-aldol reactions of a-dicarbonyl compounds see:Ramirez, F.; Ramanathan, N.; Desai, N. B. J. Am. Chem. Soc 1962, 84, 1317.
30. Ramirez, F. Synthesis 1974, 90.
31. The 1H NMR spectrum of this product (42) as well as those of the related benzazepine structures 13 and 34 all show a distinctive broadening of the ethylene protons between nitrogen and the aromatic ring relative to the corresponding acyclic precursors.
32. An alternative possibility is that the benzylic carbon-oxygen bond in enediolate 43 undergoes heterolysis to give a carbenoid intermediate which adds to the thiolactam to give episulfide 45 directly.
33. Roth, M.; Dubs, P.; Götschi, E.; Eschenmoser, A. Helu. Chim. Acta 1971, 54 (2), 710.