UC Berkeley

Using calculations, we show that a proposed Cu(I)-mediated deconstructive fluorination of N-benzoylated cyclic amines with Selectfluor^® is feasible and may proceed through: (a) substrate coordination to a Cu(I) salt, (b) iminium ion formation followed by conversion to a hemiaminal, and (c) fluorination involving C-C cleavage of the hemiaminal. The iminium ion formation is calculated to proceed via a F-atom coupled electron transfer (FCET) mechanism to form, formally, a product arising from oxidative addition coupled with electron transfer (OA + ET). The subsequent β-C-C cleavage/fluorination of the hemiaminal intermediate may proceed via either ring-opening or deformylative fluorination pathways. The latter pathway is initiated by opening of the hemiaminal to give an aldehyde, followed by formyl H-atom abstraction by a TEDA²⁺ radical dication, decarbonylation, and fluorination of the C3-radical center by another equivalent of Selectfluor^®. In general, the mechanism for the proposed Cu(I)- mediated deconstructive C-H fluorination of N-benzoylated cyclic amines (LH) by Selectfluor^® was calculated to proceed analogously to our previously reported Ag(I)-mediated reaction. In comparison to the Ag(I)-mediated process, in the Cu(I)-mediated reaction the iminium ion formation and hemiaminal fluorination have lower associated energy barriers, whereas the product release and catalyst re-generation steps have higher barriers.