Solution and solid-phase synthesis of functionalized 3-arylbenzofurans by a novel cyclofragmentation - Release pathway

Angewandte Chemie - International Edition

Volumn 39, Issue 6, 2000, Pages 1093-1096

  Nicolaou, K C ^a,b   Snyder, Scott A ^a,b   Bigot, Antony ^a,b   Pfefferkorn, Jeffrey A ^a,b  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Benzofurans; Combinatorial chemistry; Heterocycles; Solid phase synthesis

Indexed keywords

BENZOFURAN DERIVATIVE;

ARTICLE; CHEMICAL ANALYSIS; CHEMICAL REACTION; CHEMICAL STRUCTURE; STRUCTURE ANALYSIS; SYNTHESIS;

EID: 0043227327     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1521-3773(20000317)39:6<1093::AID-ANIE1093>3.0.CO;2-S     Document Type: Article

References (51)

1. a) P. Cagniant, D. Cagniant in Advances in Heterocyclic Chemistry, Vol. 18 (Eds.: A. R. Katritzky, A. J. Boulton), Academic Press, New York, 1975, pp. 337-482;
2. b) A. Mustafa in Chemistry of Heterocyclic Compounds, Vol. 29 (Eds.: A Weissberger, E. C. Taylor), Wiley, New York, 1974, pp. 1-514.
3. Although nucleophiles typically open epoxides at the less substituted carbon atom, we envisaged that this steric bias could be overcome by the electron-donating effect of the two aryl rings, which would sufficiently stabilize any cationic character at the quaternary center to facilitate preferential nucleophilic opening at that site. In general, Lewis acid catalysts are required to direct the attack of the nucleophile preferentially at such a position (see A. Mordini, S. Bindi, S. Pecchi, A. Capperucci, A. Degl'Innocenti, G. Reginato, J. Org. Chem. 1996, 61, 466-468).
4. For related fragmentations, see a) C. A. Grob, W. Baumann, Helv. Chim. Acta 1955, 38, 594-610;
5. b) G. Stork, H. K. Landesmann, J. Am. Chem. Soc. 1956, 78, 5129-5130;
6. c) C. A. Grob, Experientia 1957, 13, 126;
7. d) P. S. Wharton, J. Org. Chem. 1961, 26, 4781;
8. e) E. J. Corey, R. B. Mitra, H. Hota, J. Am. Chem. Soc. 1963, 85, 362-363;
9. f) E. J. Corey, R. B. Mitra, H. Hota, J. Am. Chem. Soc. 1964, 86, 485-492;
10. g) P. S. Wharton, Y. Sumi, R. A. Kretchmer, J. Org. Chem. 1965, 30, 234-237;
11. h) P. S. Wharton, G. A. Hiegel, J. Org. Chem. 1965, 30, 3254-3257;
12. i) G. Ohloff, J. Becker, K. H. Schulte-Elte, Helv. Chim. Acta 1967, 50, 705-708;
13. j) A. Eschenmoser, D. Felix, G. Ohloff, Helv. Chim. Acta 1967, 50, 708-713;
14. k) C. A. Grob, P. Schiess, Angew. Chem. 1967, 79, 1-15; Angew. Chem. Int. Ed. Engl. 1967, 6, 1-15;
15. k) C. A. Grob, P. Schiess, Angew. Chem. 1967, 79, 1-15; Angew. Chem. Int. Ed. Engl. 1967, 6, 1-15;
16. l) C. A. Grob, Angew. Chem. 1969, 81, 543-554; Angew. Chem. Int. Ed. Engl. 1969, 8, 535-546;
17. l) C. A. Grob, Angew. Chem. 1969, 81, 543-554; Angew. Chem. Int. Ed. Engl. 1969, 8, 535-546;
18. m) D. Felix, J. Schreiber, G. Ohloff, A. Eschenmoser, Helv. Chim. Acta 1971, 54, 2896-2912;
19. n) A. Fischli, Q. Branca, J. Daly, Helv. Chim. Acta 1976, 59, 2443-2461;
20. o) D. Sternbach, M. Shibuya, F. Jaisli, M. Bonetti, A. Eschenmoser, Angew. Chem. 1979, 91, 670-671; Angew. Chem. Int. Ed. Engl. 1979, 18, 634-636;
21. o) D. Sternbach, M. Shibuya, F. Jaisli, M. Bonetti, A. Eschenmoser, Angew. Chem. 1979, 91, 670-671; Angew. Chem. Int. Ed. Engl. 1979, 18, 634-636;
22. p) M. Shibuya, F. Jaisli, A. Eschenmoser, Angew. Chem. 1979, 91, 675-676; Angew. Chem. Int. Ed. Engl. 1979, 18, 636-637.
23. p) M. Shibuya, F. Jaisli, A. Eschenmoser, Angew. Chem. 1979, 91, 675-676; Angew. Chem. Int. Ed. Engl. 1979, 18, 636-637.
24. N1 reaction leading to the formation of 4 from 2a.
25. E. J. Corey, M. Chaykovsky, J. Am. Chem. Soc. 1962, 84, 3782-3783.
26. In the case of 12, some rearrangement of the epoxide to the corresponding aldehyde was noted prior to cyclization, which accounts for the lower yield observed (see A. Kumar, R. Singh, A. K. Mandal, Synth. Commun. 1982, 12, 613-619).
27. Pyridines are readily N-oxidized when exposed to mCPBA: however, in this case we found that sulfide oxidation occurred in preference to N-oxide formation as long as only 2.0 equivalents of mCPBA were utilized at 0 C.
28. For previous solid-phase syntheses of benzofurans, see a) A. Routledge, C. Abell, S. Balasubramanian, Synlett 1997, 61-62;
29. b) D. Fancelli, M. C. Fagnola, D. Severino, A. Bedeschi, Tetrahedron Lett. 1997, 38, 2311-2314;
30. c) H.-C. Zhang, B. E. Maryanoff, J. Org. Chem. 1997, 62, 1804-1809;
31. d) X. Du, R. W. Armstrong, J. Org. Chem. 1997, 62, 5678-5679;
32. e) T. L. Boehm, H. D. H. Showalter, J. Org. Chem. 1996, 61, 6498-6499. For the use of polymer-supported reagents in the synthesis of 3-arylbenzofurans, see
33. f) J. Habermann, S. V. Ley, R. Smits, J. Chem. Soc. Perkin Trans. 1 1999, 2421-2423.
34. For example, in solution studies neither the sulfide nor the sulfoxide congeners of 2 underwent the desired cyclofragmentation upon treatment with base to give 3-phenylbenzofuran (1); thus, generation of the sulfone activated the resin for cleavage. Moreover, a failure in any previous step (Grignard addition, alcohol oxidation, or epoxidation) would result in a structure incapable of undergoing the cyclofragmentation-release cascade.
35. Our laboratory has been engaged for several years in the development of novel resins and improved linking and release strategies, see a) K. C. Nicolaou, N. Winssinger, J. Pastor, F. Murphy, Angew. Chem. 1998, 110, 2677-2680; Angew. Chem. Int. Ed. 1998, 37, 2534-2537;
36. Our laboratory has been engaged for several years in the development of novel resins and improved linking and release strategies, see a) K. C. Nicolaou, N. Winssinger, J. Pastor, F. Murphy, Angew. Chem. 1998, 110, 2677-2680; Angew. Chem. Int. Ed. 1998, 37, 2534-2537;
37. b) K. C. Nicolaou, J. Pastor, N. Winssinger, F. Murphy, J. Am. Chem. Soc. 1998, 120, 5132-5133;
38. c) K. C. Nicolaou, N. Winssinger, J. Pastor, S. Ninkovic, F. Sarabia, Y. He, D. Vourloumis, Z. Yang, T. Li, P. Giannakakou, E. Hamel, Nature 1997, 387, 268-272;
39. d) K. C. Nicolaou, N. Winssinger, D. Vourloumis, T. Oshima, S. Kim, J. Pfefferkorn, J.-Y. Xu, T. Li, J. Am. Chem. Soc. 1998, 120, 10814-10826;
40. e) K. C. Nicolaou, N. Winssinger, J. Pastor, D. Frederik, J. Am. Chem. Soc. 1997, 119, 449-450;
41. f) K. C. Nicolaou, J. A. Pfefferkorn, G.-Q. Cao, S. Kim, J. Kessabi, Org. Lett. 1999, 1, 807-810;
42. g) K. C. Nicolaou, J. A. Pfefferkorn, G.-Q. Cao, Angew. Chem. 2000, 112, 750-755; Angew. Chem. Int. Ed. 2000, 39, 734-739;
43. g) K. C. Nicolaou, J. A. Pfefferkorn, G.-Q. Cao, Angew. Chem. 2000, 112, 750-755; Angew. Chem. Int. Ed. 2000, 39, 734-739;
44. h) K. C. Nicolaou, G.-Q. Cao, J. A. Pfefferkorn, Angew. Chem. 2000, 112, 755-759; Angew. Chem. Int. Ed. 2000, 39, 739-743.
45. h) K. C. Nicolaou, G.-Q. Cao, J. A. Pfefferkorn, Angew. Chem. 2000, 112, 755-759; Angew. Chem. Int. Ed. 2000, 39, 739-743.
46. To the best of our knowledge, most previously described polystyrene thiophenol resins contain an aliphatic amide spacer between the polymer backbone and the thiophenol moiety (see I. Parrot, C.-G. Wermuth, M. Hibert, Tetrahedron Lett. 1999, 40, 7975-7978). Since the abstraction of protons adjacent to the amide functionality during the KOtBu cleavage step might interfere with product release, we sought to prepare a spacerless resin.
47. J. M. Farrall, J. M. J. Fréchet. J. Org. Chem. 1976, 41, 3877-3882.
48. K. Smith, D. Hou, J. Org. Chem. 1996, 61, 1530-1532.
49. While numerous polystyrene sulfinic acid resins are available, most are used as scavenger resins (for example, Dowex WX4-50), and hence are too highly loaded to be practical for solid-phase organic synthesis.
50. K. Fujimori, H. Togo, S. Oae, Tetrahedron Lett. 1980, 21, 4921-4924.
51. N. Ono, H. Miyake, T. Saito, A. Kaji, Synthesis 1980, 952-953.