Outer-Sphere Mechanism for the Hydrogenation of Ketones and Imines

Outer-Sphere Mechanism for the Hydrogenation of Ketones and Imines 

The immediate product from the reaction of the hydride complex with ketone has been a subject of debate. Some have proposed that an alkoxide complex is formed and that proton transfer between the coordinated amine and the alkoxide then forms the alcohol that is ultimately released. Others have supported a direct transfer to form free alcohol (or amine) and then coordination of this species to the open To accommodate the isotope effect data and the absence of an open coordination site for coordination of the ketone, the formation of the alkoxide from the hydride has been proposed to occur by hydride transfer assisted by hydrogen bonding of the amine in the case of the reactions with [Ru(BINAP)(diamine)(H)j], or by ring slip to allow coordination of the ketone (or imine) in the case of the reactions with the Shvo catalyst.  

A recent study by Bergens provided important data on this issue. This study showed that the reaction of a ketone with [Ru(BINAP)(diamine)(H)j] forms an alkoxide complex at low temperature. In the presence of a different alcohol than that formed by the reduction, the initial alkoxide complex is the one that results from the reduction of the ketone. These data imply that the transfer of the hydride occurs by a mechanism that forms alkoxide with assistance by hydrogen bonding of the ketone to the amine, without coordination of the ketone to the metal, and without releasing free alcohol. 

These data can be accommodated by a simultaneous addition of the hydride and proton to form an alcohol that is initially hydrogen bonded to the amine and forms the alkoxide without dissociation of free alcohol or by a transition state with a structure resembling those proposed for the direct, simultaneous transfer of the hydride and proton, but leading to the alkoxide complex directly. After this transfer of the hydride to form an alkoxide, a base-assisted elimination of the alkoxide to form the amide complex is proposed to occur. This step parallels the classic conjugate-base mechanism for dissociative Hgand substitution discussed in Chapter 5. 

The resulting unsaturated amido complex then reacts with in the hydrogenation 

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