Enantio- and diastereoselective synthesis of the AB ring system of aklavinone by coupling a chemoenzymatic procedure with organometal chemistry

Tetrahedron

Volumn 52, Issue 42, 1996, Pages 13493-13512

  Banfi, Luca ^a   Guanti, Giuseppe ^a   Riva, Renata ^a  

^a UNIVERSITY OF GENOA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

AKLAVINONE; NAPHTHALENE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; PRIORITY JOURNAL; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0030583518     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4020(96)00804-6     Document Type: Article

References (62)

1. 1. Part of this work was reported in preliminary communications [a) Guanti, G.; Banfi, L.; Brusco, S.; Riva, R. Tetrahedron Lett. 1993, 34, 8549-8552;
2. b) Guanti, G.; Riva, R. Tetrahedron Lett. 1995, 36, 3933-3936].
3. 2. For some excellent reviews in the field of anthracyclinones see: a) Krohn, K. Angew. Chem., Int. Ed. Engl., 1986, 25, 790-807;
4. b) Krohn, K. Tetrahedron 1990, 46, 291-318;
5. c) Thomas, J. I. 'Synthesis of Anthracyclines related to Daunomycin', in Recent Progress in the Chemical Synthesis of Antibiotics, Lukas, G.; Ohno, M. Eds., Springer, Berlin, 1990, p. 467-496.
6. 3. Syntheses of 1: a) McNamara, J. M.; Kishi, Y. Tetrahedron 1984, 40, 4685-4691;
7. b) Rizzi, J. P.; Kende, A. S. Tetrahedron 1984, 40, 4693-4700; syntheses of AB ring fragment 2:
8. c) Meyers, A. I.; Higashiyama, K. J. Org. Chem. 1987, 52, 4592-4597;
9. d) Davis, F. A.; Kumar, A. Tetrahedron Lett. 1991, 32, 7671-7674.
10. 4. Guanti, G.; Banfi, L.; Riva, R. Tetrahedron 1994, 50, 11945-11966.
11. 5. Kitahara, T.; Touhara, K.; Watanabe, H.; Mori, K. Tetrahedron 1989, 45, 6387-6400.
12. 2 to ensure its stability over a long period of time; alternatively the best way is to freshly prepare this reagent (ref. Connor, D. S.; Klein, G. W.; Taylor, G. N.; Boeckmann R. K.; Medwid J. B. Org. Synth., coll. vol. VI, 101-103).
13. 2NH either to the organic extract or to the eluent for chromatography on silica; but we never obtained pure 14 in acceptable yield and purity, although, as we found out lather, this compound is perfectly stable on silica, also without use of additives.
14. 8. As we verified later on similar intermediates, compounds like 9 are activated to elimination processes under basic conditions: we frequently obtained elimination products like 21 (also in this case it was detected, even in small quantities, in the reaction mixture); probably, the presence of methanol gave in this case a Michael-type reaction, responsible for the formation of 10. (equation presented)
15. 9. The reduction of the ester was never complete, also using an excess of DIBALH and was always accompanied by a small amount of the corresponding aldehyde; however the mixture can be oxidized as such to give 12.
16. 10. The direct homologation of ester 9 via Claisen-type reaction (re. a) Rathke, M. W.; Lindert, A. J. Am. Chem. Soc. 1971, 93, 2318-2320;
17. b) Winkler, J. D.; Hershberger, P. M.; Springer, J. P. Tetrahedron Lett. 1986, 27, 5177-5180;
18. c) Pettersson, L.; Frejd, T.; Magnusson, G. Tetrahedron Lett. 1987, 28, 2753-2756) gave only a low conversion to desired 14 (24%).
19. 11. a) Bram, G.; Vilkas, M. Bull. Chem. Soc. Fr. 1964, 945-951;
20. b) Shih, D. H., Baker, F., Cama, L.; Christensen, B. G. Heterocycles 1984, 21, 29-40.
21. 12. A debenzylation method using boron trifluoride in the presence of a thiol is known (rif. Fuji, K.; Ichikawa, K.; Node, M.; Fujita, E. J. Org. Chem. 1979, 44, 1661-1664).
22. 13. The resulting hydroxy ester rapidly cyclizes to give the six membered lactone 22 as soon as the carbonyl group is protected, but we never were able to utilize this lactone as intermediate for our synthetic purposes.
23. (equation presented) 14. Use of purified 1,2-bis[(trimethylsilyl)thio]ethane (rif. Evans, D. A.; Truesdale, L. K.; Grimm, K. G.; Nesbitt, S. L. J. Am. Chem. Soc. 1977, 99, 5009-5017) under catalysis of various Lewis acids gave no protected 18.
24. 15. Also here, as reported in ref. 4, 1,8-dihydroxytetralins 19 and 21 were best characterized as the corresponding diacetates 20 e 22.
25. 16. a) Guanti, G.; Narisano, E.; Podgorski, T.; Thea, S.; Williams, A. Tetrahedron Lett. 1990, 46, 7081-7092;
26. b) Guanti, G.; Banfi, L.; Narisano E. J. Org. Chem. 1992, 57, 1540-1554.
27. 17. a) Guanti, G.; Banfi, L.; Riva, R. Tetrahedron: Asymmetry 1994, 5, 9-12;
28. b) Banfi, L.; Guanti, G.; Riva, R. Tetrahedron: Asymmetry 1995, 6, 1345-1356.
29. 1a
30. 19. Diol 24 was prepared according to ref. 17b.
31. 3a that the correct stereochemistry of carbon 7 of 1 (1 in compound 19) can be established as the last step of the synthetic transformations by the stereospecific introduction of the hydroxy group in the a position respect to ring.
32. 1H-n.m.r. analysis of the corresponding Mosher's esters (ref. Sullivan, G. R.; Dale, J. A.; Mosher, H. S. J. Org. Chem. 1973, 38, 2143-2147).
33. 2O) gave deblocking of TBDPS group (27%) and lactonization to the analogous of 22 (54%).
34. b) Conditions used successfully on 14 gave the same result.
35. c) Conditions described in note 14 failed also in this case. Moreover, our attempts to open the lactone restoring the ester function failed.
36. 23. a) Attempts to convert the carbonyl of 31a into the corresponding dioxolane by treatment with ethylene glycol in the presence of camphorsulfonic acid gave partial hydrolysis of the ester function (39%) together with transesterification product (38%), due to the action of ethylene glycol;
37. b) Use of 2-methoxy-1,3-dioxolane gave, instead of transketalization product, only the analogous of 31a as methyl ester (22%).
38. 24. a) Classical benzylation, that is treatment of the alcohol with NaH, followed by addition of benzyl bromide, furnished 29c in low yield and extended racemization at the chiral centre.
39. 2O (ref. 1) Van Hijfte, L.; Little, R. D. J. Org. Chem. 1985, 50, 3940-3942;
40. 2) Gargiulo, D.; Blizzard, T. A.; Nakanishi, K. Tetrahedron 1989, 45, 5423-5432) gave 29c in good yield (81%) but with about 30% racemization.
41. c) Benzylation with benzyl trichloroacetimidate catalyzed by trifluoromethanesulfonic acid (ref. Nakajiama, N.; Horita, K.; Abe, R.; Yonemitsu, O. Tetrahedron Lett. 1988, 29, 4139-4142) proved to be non-racemizing, but yield of 29c was not reproducible and product, obtained by this procedure, was very difficult to purify.
42. 25. MPM showed to be very ephemeral: a) procedure reported for compound 14, gave deprotected ester (28%) together with the analogous of 22 (31%);
43. b) the mild procedure reported in note 14 gave just deblocking of MPM group;
44. c) attempts to protect ketone function after allyl removal also failed.
45. 26. Due to the intrinsic enantiodivergency of compounds like 28 or ent-28, 29c can also be prepared from 28 but through a two step longer sequence involving a supplementary protecting group (see ref. 1a).
46. 28, the racemization has necessarily occurred at the homologation step.
47. 28. Guanti, G.; Banfi, L.; Riva, R. Tetrahedron 1995, 51, 10343-10360.
48. 29. See also ref. 1a.
49. 1H-n.m.r.
50. 31. The preparation of 32 in 97% enantiomeric excess was already described in ref. 28.
51. 32. Brown, H. C.; Bhat, K. S.; Randad, R. S. J. Org. Chem. 1989, 54, 1570-1576.
52. 33. a) Banfi, L.; Guanti, G.; Narisano, E. Tetrahedron 1993, 49, 7385-7392;
53. b) Guanti, G.; Banfi, L.; Riva, R.; Zannetti, M. T. Tetrahedron Lett. 1993, 34, 5483-5486.
54. 34. A previous example of use of Hünig's base in a Swern oxidation has also been reported (ref. Walba, D. M.; Thurmes, W. N.; Altiwanger, R. C. J. Org. Chem. 1988, 53, 1046-1056).
55. 4 reduction of 33.
56. 36. A side reaction responsible for the observed low yield is the chlorination at the benzylic position of 32.
57. 37. BOM group, which was directly introduced on 28 without racemization, was in this case the protection of choice since, for the planned synthesis, we did not foresee a thioketalization step, a transformation not consistent with an acetalic-like protection.
58. 38. Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815-3818.
59. 1H-n.m.r. analysis; the two diastereomers were not separated neither at the level of 36 nor in one of the following.
60. 40. Bowers, A.; Halsall, T. G.; Jones, E. R. H.; Lemin, A. J. J. Chem. Soc. 1953, 2548-2560.
61. 41. Wessel, H.-P.; Iversen, T.; Bundle, D. R. J. Chem. Soc., Perkin Trans I 1985, 2247-2250.
62. 42. Bonini, C.; Righi, G. Tetrahedron 1992, 48, 1531-1538.