The Cp(2)TiPh-Mediated Reductive Radical Cyclization of Cyanoketones and Related Reactions. Efficient Trapping of Ketyl Radicals by Cp(2)TiPh-Coordinated Polar Multiple Bonds

The reductive radical cyclization of cyanoketones was achieved using Cp(2)TiPh. The Ti(III) reagent was prepared by the sequential addition of i-PrMgCl and PhMgBr to commercial Cp(2)TiCl(2) in this order and used effectively without isolation. The cyclization of the gamma- and delta-cyanoketones was performed in toluene at ambient temperature for several hours to give alpha-hydroxycyclopentanones and hexanones in moderate to good yields, respectively. The titanium reagent independently coordinates to both the carbonyl and cyano termini. As a result of lowering the LUMO of the cyano group upon coordination of the Ti(III) species, the irreversible cyclization successfully proceeds without formation of the unstable iminyl radical intermediate. The ester group can also be activated by the coordination of Cp(2)TiPh, and aromatic ketones with an ester group at the gamma position are cyclized to give the corresponding alpha-hydroxyketones.