Hydroamination of Dihapto-Coordinated Benzene and Diene Complexes of Tungsten: Fundamental Studies and the Synthesis of γ-Lycorane

Abstract Reactions are described for complexes of the form WTp(NO)(PMe3)(?2-arene) and various amines, where the arene is benzene or benzene with an electron-withdrawing substituent (CF3, SO2Ph, SO2Me). The arene complex is first protonated to form an ?2-arenium species, which then selectively adds the amine. The resulting ?2-5-amino-1,3-cyclohexadiene complexes can then be subjected to the same sequence with a second nucleophile to form 3-aminocyclohexene complexes, where up to three stereocenters originate from the arene carbons. Alternatively, 1,3-cyclohexadiene complexes containing an ester group at the 5 position (also prepared from an arene) can be treated with acid followed by an amine to form trisubstituted 3-aminocyclohexenes. When the amine is primary, ring closure can occur to form a cis-fused bicyclic ?-lactam. Highly functionalized cyclohexenes can be liberated from the tungsten through oxidative decomplexation. The potential utility of this methodology is demonstrated in the synthesis of the alkaloid ?-lycorane. An enantioenriched synthesis of a lactam precursor to ?-lycorane is also described. This compound is prepared from an enantioenriched version of the tungsten benzene complex. Regio- and stereochemical assignments for the reported compounds are supported by detailed 2D-NMR analysis and 13 molecular structure determinations (SC-XRD).