The Effect of the Fluorine Substitution on the Enantioselective Oxidation of Sulfides with Chiral Titanium Catalysts: A Combined Computational and Experimental Investigation

Authors

  • Dr. Maria Annunziata M. Capozzi,

    1. Dipartimento di Chimica, Università di Bari via Orabona 4. 70125 Bari (Italy)
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  • Dr. Francesco Capitelli,

    1. CNR IC via Salaria, Km 29.300, 00195 Monterotondo (Rome)
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  • Prof. Andrea Bottoni,

    Corresponding author
    1. Dipartimento di Chimica “G. Ciamician”, Università di Bologna via Selmi 2, 40126 Bologna (Italy)
    • Andrea Bottoni, Dipartimento di Chimica “G. Ciamician”, Università di Bologna via Selmi 2, 40126 Bologna (Italy)

      Cosimo Cardellicchio, CNR ICCOM—Dipartimento di Chimica, Università di Bari via Orabona 4. 70125 Bari (Italy), Fax: (+39) 0805539596

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  • Dr. Matteo Calvaresi,

    1. Dipartimento di Chimica “G. Ciamician”, Università di Bologna via Selmi 2, 40126 Bologna (Italy)
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  • Dr. Cosimo Cardellicchio

    Corresponding author
    1. CNR ICCOM—Dipartimento di Chimica, Università di Bari via Orabona 4. 70125 Bari (Italy), Fax: (+39) 0805539596
    • Andrea Bottoni, Dipartimento di Chimica “G. Ciamician”, Università di Bologna via Selmi 2, 40126 Bologna (Italy)

      Cosimo Cardellicchio, CNR ICCOM—Dipartimento di Chimica, Università di Bari via Orabona 4. 70125 Bari (Italy), Fax: (+39) 0805539596

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Abstract

The results of a combined computational-experimental study of the oxidation of various fluorinated aryl benzyl sulfides using tert-butyl hydroperoxide (TBHP) in the presence of a complex of titanium and (S,S)-hydrobenzoin are presented. As observed in previous studies for other aryl benzyl sulfides, the reaction leads to enantiopure sulfoxides (ee>98 %) in good isolated yields (81–96 %) except the case of pentafluorobenzyl pentafluorophenyl sulfide for which a lower ee (61 %) is observed. DFT computations on a model-system formed by the substrate, the oxidant TBHP and the [(S,S)-hydrobenzoin]2-Ti complex satisfactorily explain this unexpected item. The enantioselectivity is governed by the relative energy of the two diastereomeric octahedral complexes that form if TBHP approaches the initial complex between substrate and [(S,S)-hydrobenzoin]2-Ti before the oxygen transfer. For pentafluorobenzyl pentafluorophenyl sulfide, the two octahedral complexes are almost degenerate and, thus, they form in similar amounts. As the two corresponding diastereomeric transition states are similar in energy, the probability to follow one or the other diastereomeric reaction channel becomes comparable, which leads to the lower enantiomeric excess experimentally observed. Our computations indicate that the particular “folded conformation”, adopted by the substrate only if both phenyl rings are fluorinated, is the key factor that determines the near degeneracy of the two diastereomeric octahedral complexes.

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