Silver(I)-Catalyzed Insertion of Carbene into Alkane C–H Bonds and the Origin of the Special Challenge of Methane Activation Using DFT as a Mechanistic Probe

The argentate trinuclear cluster Ag3(μ2-3,5-(CF3)2PyrPy)3 (3,5-(CF3)2PyrPy = 2,2′-pyridylpyrrolide– ligand) catalytically promotes the insertion of the carbene of ethyl
diazoacetate at room temperature into the C–H bond of a series
of alkanes ranging from ethane to hexane, as well as branched and
cyclic hydrocarbons. In addition to experimental studies, we also
present theoretical studies elucidating the mechanism to C–H
activation and functionalization by the transient silver carbene monomer
(3,5-(CF3)2PyrPy)­Ag­(CHCO2Et). On
the basis of DFT studies, formation of the silver carbene complex
was found to be rate-determining for alkane substrates such as ethane
and propane. On the other hand, DFT studies on methane, a substrate
that we failed to activate, revealed that carbene insertion into the
C–H bond was overall rate-determining. Theoretical analysis
of charge flow also shows that the change from separated reagents
to the TS involves charge flow from alkane to the
silver carbene carbon with the bridging H behaving as a conduit. KIE
studies using cyclohexane as a substrate suggest that the product-determining
step involves only modest C–H bond lengthening, which can be
also represented as a very early transition state with respect to
C–H insertion of the carbene.