Abstract.
B3LYP calculations in conjunction with natural bond orbital population analysis have been performed for a previtamin D model and corresponding transition structures for the [1,7]-hydrogen migration. In addition the 19,19-difluoro, 19-methoxy and 19-fluoro substituted analogs were investigated. The calculated activation barriers decrease in the following order: CHF2>CH3>CH2OCH3 (24.8, 23.5 and 20.1 kcal/mol). This is in qualitative agreement with experiments. It has been suggested that a decrease of the barrier by a 19-methoxy substituent and its increase by a 19,19-difluoro substituent are phenomena of different origin. In the case of 19-methoxy substitution, the effect is due to the charge redistribution in the triene system and the decrease of the C(19)–H bond energy. The effect of two fluorine substituents at C-19 on the activation barrier is suggested to originate from the combination and balance of several factors: electrostatic repulsion between the negative fluorine atom and the π-electron cloud over the conjugated system, an increase of the HOMO–LUMO gap, and geminal difluoro substitution affecting C–F and C–C bond energies.
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Received: 17 May 2002 / Accepted: 11 September 2002 / Published online: 14 February 2003
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Dmitrenko, O., Bach, R., Sicinski, R. et al. Computational insight into the effect of C(19) substituents on [1,7]-hydrogen shift in previtamin D. Theor Chem Acc 109, 170–175 (2003). https://doi.org/10.1007/s00214-002-0405-3
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DOI: https://doi.org/10.1007/s00214-002-0405-3