Synthesis of ketones and aldehydes via reactions of Weinreb-type amides on solid support

Tetrahedron Letters

Volumn 37, Issue 8, 1996, Pages 1161-1164

  Dinh, Tam Q ^a   Armstrong, Robert W ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE; KETONE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS; TECHNIQUE;

EID: 0030041813     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(95)02400-X     Document Type: Article

References (13)

1. 4 with Weinreb-type amides on solid support was recently published: Fehrentz, J.-A.; Paris, M.; Heitz, A.; Velek, J.; Liu, C.-F.; Winternitz, F.; Martinez, J. Tetrahedron Lett. 1995, 36, 7871-7874.
2. For recent reviews, see: a) Felder, E. D. Chimia 1994, 48, 531-541.
3. b) Gallop, M. A.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gordon, E. M. J. Med. Chem. 1994, 37, 1233-1251 and 1385-1401.
4. For a review, see: Gokel, G.; Ludke, G.; Ugi, I. Four-Component Condensations and Related Reactions. In Isonitrile Chemistry; Ugi, I., Ed.; Academic Press: New York, 1971; pp. 145-199.
5. Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815-3818.
6. 2, rt, 10 min.
7. 2, rt, 1 hr.
8. 1HMR data.
9. Miknis, G. F.; Williams, R. M. J. Am. Chem. Soc. 1993, 115, 536-547.
10. Darwish, I. S.; Patel, C.; Miller, M. J. J. Org. Chem. 1993, 58, 6072-6075.
11. In the crude products of some reactions, impurities arising from the Grignard reagents' reaction with the THF solvent were observed.
12. 4 was used because it gave better results than DIBAH.
13. 4 reactions in Table 1, filtering and washing the unquenched resin with dry THF resulted in no aldehyde product in the filtrate. By contrast, in the PhMgCl reaction of Weinreb-type amide 16, most of the ketone product was found in the supernatant of the reaction mixture, a smaller amount of the ketone was obtained after the resin was rinsed with dry THF in the reaction flask, and no ketone was detected after the resin was quenched with acid! This peculiar behavior will be explored further.