10.1002/chem.201604507
Chemistry - A European Journal
COMMUNICATION
Calculated activation energies ΔG≠ (Table 3) for the reaction
of the four dioxiranes 1a-d with 2a correlate well with the
experimental results.18 More in detail, calculated ΔG≠ values open
to three considerations: i) “addition” of fluorine atoms increase the
electrophilic character of the oxidant, thus lowering the TS energy
for all the processes, ii) this effect is more pronounced in the case
of N-H oxidation rather that in the case of C-H, iii) while C-H
oxidations are favored by DDO, in the case of TFDO the two
activation energies (ΔG≠) are similar. In the latter, the CF3 group
is able to delocalize more effectively along the oxidation pathway
the negative charge developing at the “leaving” oxygen atom.19
This polarization is evident in the NBO calculated amount of
charge transferred in the TS (Fig. 4).
The calculated energies pair with the two observed reaction
pathways, which substantially occur through a 1e and a 2e
mechanism, respectively. The CF3 group in the TFDO, owing to
its strong electron-withdrawing nature, is able to better stabilize
the charge transfer required for the heterolytic pathway. The N-H
oxidation occurs via a “more polarized” TS, and this difference
accounts for the observed switch of chemoselectivity of the two
oxidants. On the basis of the gathered data for lactam 2a, it is
possible to ascribe the trends observed in the different lactams
series to the higher energy required by the C-H bond to get
perpendicular to the amide plane in order to react and by the
different amide geometries depending upon ring size.14,20
In conclusion, results from experiments and theoretical
calculations support the view that the polar TS arising from
interaction of the nitrogen atom with dioxiranes can be more easily
accessible by TFDO. The CF3 group is able to stabilize the “2e
flow” better than the corresponding methyl substituted DDO. On
the contrary, an “oxygen rebound” mechanism, featuring the
dioxirane oxidation of C-H, goes through lower-energy TS’s for
DDO, most likely because of the higher propensity of the latter to
undergo O-O homolysis. The study has also offered the possibility
to use two new oxidants 1b,c as a novel physical organic
chemistry “tool” for the determination of the homo- vs heterolytic
character of oxidations. These results draw also the attention to
the fact that the complex chemistry of oxidations is highly
determined by the intrinsic characteristics of the oxidant moiety
which is not transferred, the formal “leaving group”, rather than
the features present at the reactant state.21
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Acknowledgements
This research was supported by: Regione Puglia MIUR PON Ri-
cerca e Competitività 20072013 Avviso 254/Ric. del 18/05/2011,
Project PONa3 00369 “Laboratorio SISTEMA”, Università di Pa-
dova (PRAT-CPDA123307 and CPDA153122), MIUR (PRIN-
2010-11 2010CX2TLM_002). Commercial Caroat® triple salt was
kindly supplied by Peroxide-Chemie, (Degussa, Germany). The
work has been carried out in the frame of COST Action CM1205
CARISMA ‘Catalytic Routines for Small Molecules Activation’.
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Keywords: Oxidation • Dioxiranes • Lactams • Oxidation
chemoselectivity • MP2 calculations
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