Using nucleophilic substitution reactions to understand how a remote alkyl or alkoxy substituent influences the conformation of eight-membered ring oxocarbenium ions

Organic Letters

Volumn 6, Issue 25, 2004, Pages 4739-4741

  Chamberland, Stephen ^a   Woerpel, K A ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBENOID; OXOCARBENIUM; UNCLASSIFIED DRUG;

ARTICLE; CONFORMATION; CRYSTAL; ELECTRICITY; ENERGY; MATHEMATICAL MODEL; SUBSTITUTION REACTION; X RAY CRYSTALLOGRAPHY;

ACETATES; ALKYLATION; CYCLIZATION; HYDROCARBONS; IONS; METHANE; MODELS, CHEMICAL; OXOCINS; STEREOISOMERISM;

EID: 11444254434     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol047998d     Document Type: Article

References (32)

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19. Details of calculations are provided as Supporting Information.
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21. Numbering in this paper considers the carbocationic carbon as C-1.
22. For these reactions, a small nucleophile, trimethylsilyl cyanide (Evans, D. A.; Carroll, G. L.; Truesdale, L. K. J. Org. Chem. 1974, 39, 914-917), was chosen to minimize steric effects in the transition state that might perturb the inherent conformational preferences of the charged intermediates. Lewis acid-mediated nucleophilic substitution of 10a and 15a with another small nucleophile, diethyl-2-phenylethynylalane, gave selectivities comparable to those reactions using trimethylsilyl cyanide as the nucleophile.
23. Mixtures of diastereomeric acetates (the syntheses of acetates are contained in Supporting Information) were used in these reactions. Control experiments indicate that diastereomeric acetates give the same product with largely the same degree of selectivity. These control experiments strongly suggest that the reaction operates by a dissociative mechanism. If direct displacement occurred, the selectivity should reflect the initial acetate ratio.
24. 1H NMR spectra of unpurified reaction mixtures. The relative stereochemistry of the major product was not proven for unselective reactions (C4- and C5-methyl) but was postulated to be cis on the basis of computational results (ref 10). For nitrile 4b, the relative stereochemistry was proven by X-ray crystallography.
25. 4) employed. A table of comparative selectivities appears in Supporting Information.
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29. + bond are of standard lengths (1.4 and 1.27 Å, respectively, ref 9b).
30. + bond are of standard lengths (1.4 and 1.27 Å, respectively, ref 9b).
31. Theoretical experiments suggest that a bridged bicyclic oxonium ion is the global minimum of this intermediate, but we do not believe that this conformation can be used to explain the diastereoselectivity of this reaction. Further explanation is provided within Supporting Information.
32. An extreme example of transannular stabilization is seen for μ-hydrido bridged carbocations. See: Ponec, R.; Yuzhakov, G.; Tantillo, D. J. J. Org. Chem. 2004, 69, 2992-2996 and references cited therein.