A Mild and Chemoselective Method for the Reduction of Conjugated Isoxazolines to β-Hydroxy Ketones

Organic Letters

Volumn 3, Issue 10, 2001, Pages 1587-1590

  Bode, Jeffrey W ^a   Carreira, Erick M ^a  

^a ETH ZURICH   (Switzerland)

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EID: 0003609837     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol015885d     Document Type: Article

References (19)

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2. (b) Torssell, K. B. G. Nitrile Oxides, Nitrones, and Nitronates in Organic Chemistry; VCH: Stuttgart, 1988.
3. (a) Curran, D. P. J. Am. Chem. Soc. 1983, 105, 5826.
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8. For examples, see: (a) McGarvery, G. J.; Mathys, J. A.; Wilson, K. J. J. Org. Chem. 1996, 61, 5704-5705.
9. (b) Zheng, W.; DeMattei, J. A.; Wu, J.-P.; Duan, J. J.-W.; Cook, L. R.; Oinuma, H.; Kishi, Y. J. Am. Chem. Soc. 1996, 118, 7946-7968.
10. Bode, J. W.; Carreira, E. M. J. Am. Chem. Soc. 2001, 123, 3611-3612.
11. Isager, P.; Thomsen, I.; Torssell, K. G. B. Acta Chem. Scand. 1990, 44, 806.
12. We have recently reported the first preparation of propargylic isoxazolines by nitrile oxide cycloaddition of alkyne-substituted nitrile oxides: Bode, J. W.; Fraefel, N.; Muri, D.; Carreira, E. M. Angew. Chem., Int. Ed. 2001, 40, in press.
13. (a) Keck G. E.; McHardy, S. F.; Wager, T. T. Tetrahedron Lett. 1995, 41, 7419
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15. 4, and concentrated under reduced pressure. Purification by flash cnromatography (6:1 hexanes/EtOAc) afforded the β-hydroxyketone (75%) as a colorless oil.
16. 2) in 96% yield.
17. 2, we observed formation of the expected product along with significant amounts of the corresponding retro-aldol product.
18. It is likely that the selectivity that is observed results from the difference in reduction potential of the substrate as a function of the substitution of the isoxazoline at C(3). Calculations (PC Spartan Pro, Wavefunction, Inc.) of the LUMO energies of isoxazolines i-iii revealed the ranking to be iii > ii > i, consistent with the observed reactivity trends in which i undergoes reduction preferentially over ii and above all over iii. (matrix presented)
19. D, and elemental analyses.