Electrophilic and nucleophilic reactivities of the azomethine carbon of SAMP-hydrazones: Stereoselective synthesis of gamma-amino ketone derivatives

A novel methodology for the asymmetric synthesis of secondary N-Boc-protect ed gamma-amino ketones is described. After the highly diastereoselective nu cleophilic 1,4-addition of formaldehyde SAMP-hydrazone 1 to prochiral conju gated enones 2, the carbonyl group of the resulting li-oxo aldehyde SAMP-hy drazones 4 was protected as ethylene ketals 5. The stereoselective (de 58-8 8%) 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 re duced by Raney nickel-catalyzed hydrogenolysis of the N-N bond to afford th e corresponding amines, which were isolated as their corresponding N-Boc de rivatives 11. Noteworthy, the azomethine carbon of SAMP-hydrazones, not bei ng essentially modified during the process, sequentially serves as a nucleo philic and an electrophilic center, acting as a nexus between the conjugate d enone (electrophile) and the organometallic reagent (nucleophile) and hel ping in the creation of two adjacent stereogenic centers.