Synthesis of 3,4,5-Trisubstituted cyclohexanones by cycloaddition to solid phase 2-Aminobutadienes

Tetrahedron Letters

Volumn 38, Issue 40, 1997, Pages 7115-7118

  Crawshaw, Melanie ^a   Hird, Nicholas W ^a   Irie, Kazuyuki ^b   Nagai, Katsunori ^b  

^a GLAXOSMITHKLINE   (United Kingdom)

^b TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOHEXANONE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; IN VITRO STUDY; REACTION ANALYSIS; STEREOCHEMISTRY; TECHNIQUE;

EID: 0030881340     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)01634-1     Document Type: Article

References (16)

1. Fringuelli, F.; Taticchi, A. Dienes in the Diels-Alder Reaction, Wiley, New York, 1990.
2. Yedida, V.; Leznoff, C. Can. J. Chem. 1980, 58, 1144.
3. a) Henke, S. IBC "Combinatorial Chemistry and Automation" Conference, Geneva 1996
4. b) Tietze, L. F.; Hippe, T., Steinmetz, A. Synlett. 1996, 1043.
5. c) Schlessinger, R. H.; Bergstrom, C. P. Tetrahedron Lett. 1996, 37, 2133.
6. Krohn, K. Angew. Chem. Int. Ed. Engl. 1993, 32, 1582.
7. Enders, D.; Meyer, O., Raabe, G., Runsink, J. Synthesis 1994, 66.
8. Enders, D.; Meyer, O., Raabe, G. Synthesis, 1992, 1242.
9. Barluenga, J.; Aznar, F., Valdes, C., Martin, A., Garcia-Granada, S., Matin, E. J. Am. Chem. Soc., 1993, 115, 4403.
10. + 257.
11. Yields were calculated based on the loading of the Merrifield resin used to synthesise the aminobutadienes.
12. HPLC was carried out using Beckman System Gold, Hypersil 3μ C18 10cm column, gradient 0% to 100% acetonitrile in 0.1%TFA/water over 40min, flow rate 0.5ml/min, and monitoring at 220nm.
13. Barluenga, J.; Aznar, F., Cabal, M.-P., Valdes, C. J. Chem. Soc. Perkin. Trans. 1 1990, 633.
14. Typical Procedure: The resin in the reaction block was pre-swelled by washing with 3×1 mL THF and then 1 mL of 0.4 M solution of maleimides in dry THF was added. The block was agitated at 500 rpm for 8 h, emptied, and then washed with 3×1 mL THF and 1×1 mL dichloromethane. With the cleavage block attached, 1 mL of 3% TFA solution in dichloromethane was added and the block shaken for 10 min and then emptied. The resin was washed with a further 1 mL dichloromethane and the combined filtrate was evaporated on a Zymark Turbovap to give products as lightly coloured oils.
15. + 325.
16. As 12 except reaction time was 4 h.