Hydrogen Atom Transfer (HAT)-Mediated Remote Desaturation Enabled by Fe/Cr-H Cooperative Catalysis

Abstract A highly selective, remote desaturation reaction, catalyzed by an iron/chromium cooperative system, generates unsaturated amides from abundant starting materials. The reaction appears to operate via a triple hydrogen atom transfer (HAT) cascade: (i) A 1,5-HAT from a remote C–H bond to an iron nitrenoid; (ii) a chromium-hydride-mediated HAT to N-center, (iii) the abstraction of a second H• from the remote organic radical by the chromium radical Cr•. Unsaturated amides and conjugated dienamides can be prepared with good regio- and stereoselectivity. The synthetic utility of this method is verified by late-stage desaturation of natural product derivatives and biologically important molecules. Cooperation between the metals controls the sites of hydrogen atom transfer.