Unsaturated Nitriles: A Domino Ozonolysis-Aldol Synthesis of Highly Reactive Oxonitriles

Journal of Organic Chemistry

Volumn 62, Issue 10, 1997, Pages 3036-3037

  Fleming, Fraser F ^a   Huang, Adrian ^a   Sharief, Vaqar A ^a   Pu, Yifang ^a  

^a DUQUESNE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0000767933     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9703818     Document Type: Article

References (26)

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8. For doubly activated alkenes prepared by selenoxide elimination see: (a) Reich, H. J.; Wollowitz, S. Org. React. 1993, 44, 1 and Table XI 254-272 in particular. (b) Liu, H.-J.; Yeh, W.-L.; Browne, E. N. C. Can. J. Chem. 1995, 73, 1135.
9. For doubly activated alkenes prepared by selenoxide elimination see: (a) Reich, H. J.; Wollowitz, S. Org. React. 1993, 44, 1 and Table XI 254-272 in particular. (b) Liu, H.-J.; Yeh, W.-L.; Browne, E. N. C. Can. J. Chem. 1995, 73, 1135.
10. (a) Liu, H.-J.; Browne, E. N. C. Can. J. Chem. 1987, 65, 1262.
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15. (a) Fleming, F. F.; Pak, J. J. J. Org. Chem. 1995, 60, 4299.
16. (b) Fleming, F. F.; Hussain, Z.; Weaver, D.; Norman, R. E. J. Org. Chem. 1997, 62, 1305.
17. Kretchmer, R. A.; Thompson, W. J. J. Am. Chem. Soc. 1976, 98, 3379.
18. Direct cyclization of the intermediate carbonyl oxide with the ketonitrile is precluded since the intermediate ozonide 4 has been isolated and characterized: Tzou, J.-R.; Huang, A.; Fleming, F. F.; Norman, R. E.; Chang, S.-C. Acta Crystallogr. 1996, C52, 1012. Dimethyl sulfide reduction of 4 affords 8 in comparable yield.
19. We prefer to name these compounds as nitriles in accordance with IUPAC nomenclature since the trivial name "α-cyanocyclohexenone" de-emphasizes the profound effect of the nitrile group on the reactivity of this compound: Fleming, F. F.; Pu, Y.; Tercek, F. J. Org. Chem., submitted.
20. General Procedure. A stream of ozone is passed through a cold (-78 °C), dichioromethane solution of the unsaturated nitrile until the distinctive blue color of ozone is observed. Ozonolysis is then terminated, and the excess ozone is displaced by passing a stream of nitrogen through the solution for 5-10 min. The solution is allowed to warm to room temperature, neat dimethyl sulfide is added, and the solution is then allowed to stir at room temperature for 5-30 h. Concentration of the crude product, followed by radial chromatography, provides the nitriles 14a-d. The syntheses of 14a and 14b require terminating the ozonolysis immediately upon observation of excess ozone, purging with nitrogen, and then the dropwise addition of dimethyl sulfide at -78 °C. Caution: Care must be taken to prevent contact with these oxonitriles since minute quantities of these compounds, particularly 14a and 14b, cause headaches.
21. Elnagdi, M. H.; Elmoghayar, M. R. H.; Elgemeie, G. E. H. Synthesis 1984, 1.
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25. Ethyl 2-methyl-4-pentenoate and ethyl 3,3-diniethyl-4-pentenoate are commercially available. Ethyl 3-hydroxy-3-methyl-5-hexenoate was prepared by a modification of the literature method: Wilson, W. K.; Baca, S. B.; Barber, Y. J.; Scallen, T. J.; Morrow, C. J. J. Org. Chem. 1983, 48, 3960. 5-Methyl-5-[(trimethylsilyl)oxy]-3-oxo-7-octenenitrile (13d) was prepared by silylation of 13c.
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