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Felkin-Anh Model from an Orbital Phase Perspective: Diastereoselectivity in Nucleophilic Addition to 2,3-Bis(trifluoromethyl)bicyclo[2.2.1]heptan-7-one

preprint
revised on 13.09.2019 and posted on 13.09.2019 by Yuji Naruse, Hayata Hibino, Atsushi Takamori

To address the electronic effect in nucleophilic addition, we often use the Felkin-Anh model, in which the most sigma-electron-withdrawing group (.sigma.EWG) at the a-position of the carbonyl should be located anti to the nucleophile approach. The diastereoselectivity is often explained by the antiperiplanar effect of the .sigma.EWG. Reetz and Frenking reported that the FMO, the LUMO in the a-substituted ketone, has greater expansion anti the .sigma.EWG. Thus, the FMO theory can also apply to this diastereoselectivity. However, there is still no explanation for why the LUMO has greater expansion anti to the .sigma.EWG and toward the nucleophile approach with this conformation, as is suggested by the FMO theory. We show here that the phase-continuous cyclic orbital interaction among nNu:--.pi.*C=O-.sigma.*C-A/vic-.sigma.*CC/gem- controls the diastereoselectivity, which is confirmed with theoretical calculations and the bond model analysis using a conformationally-fixed bicyclic molecule, 2,3-bis(trifluoromethyl)bicyclo[2.2.1]heptan-7-one 1, as a model.

Funding

Gifu University

History

Email Address of Submitting Author

naruse@gifu-u.ac.jp

Institution

Department of Materials Chemistry and Processing, Graduate School of Gifu University

Country

Japan

ORCID For Submitting Author

0000-0003-3910-9356

Declaration of Conflict of Interest

There is no conflict of interest.

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