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Anomeric effects in fluoro and trifluoromethyl piperidines: a computational study of conformational preferences and hydration

  • Nathan D. Erxleben
  • Gary S. Kedziora
  • Joseph J. UrbanEmail author
Regular Article
Part of the following topical collections:
  1. Shavitt Memorial Festschrift Collection

Abstract

A computational investigation of anomeric effects in piperidine rings bearing fluoro and trifluoromethyl substituents shows for both compounds the most pronounced evidence of the anomeric effect, as expressed as hyperconjugative delocalization of the nitrogen lone pair, in structures with the substituent in the axial position and the N–H bond in the equatorial position. This structure is the lowest-energy structure in the fluoro case but not in the trifluoromethyl case where there is an increased axial penalty associated with the CF3 group. The anomeric effect is characterized via geometrical evidence, natural bond orbital analysis, electrostatic effects, and energetic criteria. Computational results from a variety of levels of theory are presented including CCSD(T) with complete basis set extrapolation, B2PLYP-D, ωB97XD, B97-D, M06-2X, B3LYP, and MP2 allowing for a comparison of performance. The CCSD(T)/CBS results are very well represented by either B2PLYP-D or ωB97XD with moderate to large basis sets (aug-cc-pVTZ or aug-cc-pVDZ). Hyperconjugation, electrostatic effects, and steric effects play a role in the relative energetic ordering of the isomers considered.

Keywords

Stereoelectronic effect Conformation Fluorine Computational Density functional theory 

Notes

Acknowledgments

Support from the Defense Threat Reduction Agency, the Office of Naval Research (via midshipmen research funds administered by the USNA Research Office), the DoD High Performance Computing Modernization Program, and the Air Force Research Laboratory DoD Supercomputing Resource Center is gratefully acknowledged. GSK wishes to acknowledge the kind mentorship of Isaiah Shavitt, who taught him many-body methods in electronic structure theory, helped him sharpen his thinking and writing, and demonstrated the importance of attention to detail.

Supplementary material

214_2014_1491_MOESM1_ESM.docx (416 kb)
Supplementary material 1 (DOCX 416 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg (outside the USA) 2014

Authors and Affiliations

  • Nathan D. Erxleben
    • 1
  • Gary S. Kedziora
    • 2
  • Joseph J. Urban
    • 1
    Email author
  1. 1.Chemistry DepartmentUnited States Naval AcademyAnnapolisUSA
  2. 2.Engility CorporationWright-Patterson AFBUSA

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