A Demonstration of the Primary Stereoelectronic Effect in the Baeyer–Villiger Oxidation of α-Fluorocyclohexanones
Cathleen M. Crudden Dr.
Department of Chemistry University of New Brunswick Fredericton, New Brunswick P.O. Box 45222, E3B 6E2 (Canada) Fax: (+1) 506-453-4981
Search for more papers by this authorAustin C. Chen
Department of Chemistry University of New Brunswick Fredericton, New Brunswick P.O. Box 45222, E3B 6E2 (Canada) Fax: (+1) 506-453-4981
Search for more papers by this authorLarry A. Calhoun Dr.
Department of Chemistry University of New Brunswick Fredericton, New Brunswick P.O. Box 45222, E3B 6E2 (Canada) Fax: (+1) 506-453-4981
Search for more papers by this authorCathleen M. Crudden Dr.
Department of Chemistry University of New Brunswick Fredericton, New Brunswick P.O. Box 45222, E3B 6E2 (Canada) Fax: (+1) 506-453-4981
Search for more papers by this authorAustin C. Chen
Department of Chemistry University of New Brunswick Fredericton, New Brunswick P.O. Box 45222, E3B 6E2 (Canada) Fax: (+1) 506-453-4981
Search for more papers by this authorLarry A. Calhoun Dr.
Department of Chemistry University of New Brunswick Fredericton, New Brunswick P.O. Box 45222, E3B 6E2 (Canada) Fax: (+1) 506-453-4981
Search for more papers by this authorThe Natural Sciences and Engineering Research Council of Canada (NSERC) is gratefully acknowledged for support of this research in terms of research grants to C.C. and PGS scholarships to A.C.C. We would especially like to thank Professor Scott E. Denmark, Dr. Robert Syvret, and Dr. Claudio Sturino for helpful discussions.
Abstract
Since it was first reported in 1899 the Baeyer–Villiger reaction has become an important reaction in organic synthesis. The stereoelectronic components of this reaction have been difficult to observe because of the conformational mobility of the Criegee intermediate. Simply placing a fluorine substituent such that it interacts with the O−O bond of the peroxyester in this intermediate permits the observation of the primary stereoelectronic effect. Lactone 1 (see reaction scheme) is formed with 90 % selectivity, which demonstrates preferential migration of the equatorially substituted carbon and is in agreement with the primary stereoelectronic effect.
Supporting Information
Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2000/z14836_s.pdf or from the author.
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For a recent example where dipole minimization is predicted to be responsible for the stereochemistry of the reaction, see: J. M. Concellón, P. L. Bernad, J. A. Pérez-Andrés, Angew. Chem. 1999, 111, 2528; Angew. Chem. Int. Ed. 1999, 38, 2384.
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- 21 In the isomeric 8ax series, the situation is different since equatorial attack puts the C−F and C−OO substituents at a dihedral angle of 60°, while axial attack puts these two at an angle of 180°. However, the conformer which activates the CH2 substituent is not affected by any serious dipole/dipole interactions. See Supporting Informationfor a graphical representation.23
- 22 Compounds 13 and 14 were separated by column chromatography and their structures determined by analysis of 1H, 13C, 19F, HMQC, HMBC, COSY, and TOCSY experiments. NOE difference experiments carried out on both 13 and 14 demonstrated that the major compound had a cis relationship between the fluorine of the oxidized substituent and the tert-butyl group, indicating that the migration had occurred, as expected, from the carbon with the equatorially disposed fluorine atom. Compound 13 was more sensitive to hydrolysis than its isomer 14 and we were thus unable to obtain spectra of 13 unencumbered by the side product of this reaction. As compound 13 was still present in substantial amounts, and as the resonances of interest are clearly separated, we were able to assign the structure from these spectra.
- 23 Experimental details, stereoelectronic analysis of Criegee intermediate resulting from axial attack of mCPBA on ketone 5ax, and spectroscopic characterization of compounds 6eq, 6ax, 7eq, 7ax, 10, 11, 13, and 14 are available as supporting information.
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