Unsaturated oxo-nitriles: Stereoselective, chelation-controlled conjugate additions

Journal of Organic Chemistry

Volumn 64, Issue 23, 1999, Pages 8568-8575

  Fleming, Fraser F ^a   Guo, Jianping ^a   Wang, Qunzhao ^a   Weaver, Douglas ^b  

^a DUQUESNE UNIVERSITY   (United States)

^b BRISTOL MYERS SQUIBB COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 HYDROXY 4 METHYL 6 OXOCYCLOHEX 1 ENECARBONITRILE; ALKOXIDE; NITRILE; UNCLASSIFIED DRUG;

ARTICLE; CHELATION; CHEMICAL REACTION; CONJUGATION; PROTON TRANSPORT; STEREOCHEMISTRY; SYNTHESIS;

EID: 0033550177     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9909709     Document Type: Article

References (61)

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50. Direct treatment of 10 with various silylating reagents causes dehydration to the aromatic nitrile 22.
51. Prepared using the procedure developed by Taber and Ruckle: Taber, D. F.; Ruckle, R. E., Jr. J. Am. Chem. Soc. 1986, 108, 7686.
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53. For leading references see: (a) Blanc, D.; Henry, J.-C.; Ratovelomanana-Vidal, V.; Genet, J.-P. Tetrahedron Lett. 1997, 38, 6603. (b) Taber, D. F.; Silverberg, L. J. Tetrahedron Lett. 1991, 32, 4227. (c) Medson, C.; Smallridge, A. J.; Trewhella, M. A. Tetrahedron: Asymmetry 1997, 8, 1049.
54. For leading references see: (a) Blanc, D.; Henry, J.-C.; Ratovelomanana-Vidal, V.; Genet, J.-P. Tetrahedron Lett. 1997, 38, 6603. (b) Taber, D. F.; Silverberg, L. J. Tetrahedron Lett. 1991, 32, 4227. (c) Medson, C.; Smallridge, A. J.; Trewhella, M. A. Tetrahedron: Asymmetry 1997, 8, 1049.
55. The stereochemistry was determined by spectral comparison of 34a with the hydroxyl analogue 21. Furthermore, the diastereomeric silyl ether derived from 20a exhibits distinctly different spectral data than that of 34a (see the Experimental Section for details).
56. The discussion of facial selectivity assumes that the preferred conformation has the smaller TBDMS ether in the axial orientation as shown: Eliel, E. L.; Wilen, S. H.; Mander, L. N. In Stereochemistry of Organic Compounds; Wiley: New York, 1994; pp 696-7.
57. Our aim was to access both conjugate addition diastereomers through a stereoelectronically controlled conjugate addition to 28b and a stereocomplementary chelation-controlled addition to the hydroxyl analogue (28b, TBDMS = H). The synthesis of the desired alcohol (28b, TBDMS = H) directly parallels Scheme 4 and provides the desired oxo-nitrile (28b, TBDMS = H) in good yield. Unfortunately this oxo-nitrile decomposes readily on purification, preventing our efforts toward implementing this stereochemical strategy.
58. The conformational preference shown is based on the large axial couplings of the methine proton (J = 13 Hz for the peak width at half-height).
59. The inseparable diastereomers were assigned by spectral comparison of the major diastereomer with 21 since 35 and 21 adopt a common conformation and have identical spectral signatures.
60. For general experimental procedures, see: Fleming, F. F.; Hussain, Z.; Weaver, D.; Norman, R. E. J. Org. Chem. 1997, 62, 1305.
61. Rathke, M. W. J. Am. Chem. Soc. 1970, 92, 3222.