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The Effect of the Fluorine Substitution on the Enantioselective Oxidation of Sulfides with Chiral Titanium Catalysts: A Combined Computational and Experimental Investigation
Author(s) -
Capozzi Maria Annunziata M.,
Capitelli Francesco,
Bottoni Andrea,
Calvaresi Matteo,
Cardellicchio Cosimo
Publication year - 2013
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201200456
Subject(s) - diastereomer , chemistry , enantioselective synthesis , aryl , catalysis , transition state , enantiopure drug , substrate (aquarium) , sulfide , enantiomeric excess , computational chemistry , medicinal chemistry , organic chemistry , alkyl , oceanography , geology
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.