Electrophilic and Nucleophilic Reactivities of the Azomethine Carbon of SAMP-Hydrazones: Stereoselective Synthesis of γ-Amino Ketone Derivatives

A novel methodology for the asymmetric synthesis of secondary N -Boc-protected γ-amino ketones is described. After the highly diastereoselective nucleophilic 1,4-addition of formaldehyde SAMP-hydrazone 1 to prochiral conjugated enones 2, the carbonyl group of the resulting 4-oxo aldehyde SAMP-hydrazones 4 was protected as ethylene ketals 5 . The stereoselective (de 58−88%) addition of organometallic reagents to the CN double bond of the latter was then performed, and the unstable intermediate hydrazines obtained were either trapped as Moc-protected hydrazines 8 in good yields (65−87%) or reduced by Raney nickel-catalyzed hydrogenolysis of the N−N bond to afford the corresponding amines, which were isolated as their corresponding N -Boc derivatives 11 . Noteworthy, the azomethine carbon of SAMP-hydrazones, not being essentially modified during the process, sequentially serves as a nucleophilic and an electrophilic center, acting as a nexus between the conjugated enone (electrophile) and the organometallic reagent (nucleophile) and helping in the creation of two adjacent stereogenic centers.