Direct and selective functionalization of unactivated substrates provides an atom-economic, cost-effective, and environment-friendly methodology in product synthesis. Transition metal catalyzed nitrene transfer reactions (MNT) are one of the enabling reactions to achieve this goal. Numerous studies of catalyst explorations have focused on steric and/or electronic effects. In this abstract, we present an alternative method to control MNT by tuning the mechanism of the product determining step in a joint computational and experimental study. We demonstrate that the ratio of the nitrene insertion between homobenzylic (β) and benzylic (α) C–H bonds can be tuned from 6:1 to 24:1 for o-propylphenylsulfonylamide by substituting the 5-position from CF3 to N-oxazolidinone in MNT by [Ag2(Py5Me2)]2+ (Py5Me2 = 2,6-bis(1,1-bis(2-pyridyl)ethyl)pyridine). Plotting Hammett σ+ values of the para-substituents against the β:α ratio yields a V-shaped Hammett correlation. Computational studies on the mechanism of the site-selective MNT show that the insertion proceeds through a concerted mechanism at the β site, furnishing a highly exothermic inserted product. In contrast, MNT to the α site proceeds through either a stepwise, producing a nearly enthalpically neutral diradical product with one unpaired electron delocalized between Ag(II)-NHR and the other between the benzylic carbon and the phenyl ring, or a concerted mechanism, yielding a highly exothermic product. The enthalpy of reaction of the product determining elementary step modulates the reaction barrier through the Bells-Evans-Polanyi principle. The ability of both the EDG and EWG to effect a stepwise MNT can be rationalized by two aspects: 1) the generated aryl radical is stabilized by both the EDG and the EWG groups and 2) the unpaired electron in Ag(II)-NHR is more localized on sterically hindered Ag center when the electron donating ability of the amide is enhanced by EDG groups. To our knowledge, this is the first example of tunable site-selective intramolecular MNT by one catalyst by changing the reaction mechanism.

Reaction mechanism as a novel approach to tune the site selectivity of transition metal catalyzed intramolecular nitrene transfer: An example using silver complexes

255th National Meeting (2018)

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