Mechanistic Studies of Ruthenium-Catalyzed Anti-Markovnikov Hydroamination of Vinylarenes:  Intermediates and Evidence for Catalysis through π-Arene Complexes

Studies are described that reveal the steps of the anti-Markovnikov hydroamination of vinylarenes with alkylamines catalyzed by Ru(COD)(2-methylallyl)2, bis(diphenylphosphino)pentane, and TfOH. Treatment of the catalyst components with an excess of styrene under the catalytic reaction conditions afforded a new ruthenium eta6-styrene complex with an ancillary tridentate PCP ligand. This ruthenium complex was active as catalyst for the hydroamination of styrene with morpholine to give the anti-Markovnikov adduct as a single regioisomer in high yield. Studies of the reactivity of the eta6-styrene complex revealed two reactions that comprise a catalytic cycle for anti-Markovnikov hydroamination: nucleophilic addition of morpholine to the ruthenium eta6-styrene complex to afford a ruthenium eta6-(2-aminoethyl)benzene complex and arene exchange of the ruthenium eta6-(2-aminoethyl)benzene complex with styrene to regenerate the ruthenium eta6-styrene complex. The addition of morpholine and the exchange of arene occurred with comparable rates. These results strongly suggest that the ruthenium-catalyzed anti-Markovnikov addition of alkylamines to vinylarenes occurs by a new reaction mechanism for hydroamination involving nucleophilic attack on the eta6-vinylarene complex and exchange of the aminoalkylarene complex product with free vinylarene. This mechanism is a rare example of catalytic chemistry through pi-arene complexes. These mechanistic data were used to select derivatives of the DPPP ligand that improve the rates of the catalytic process.