Electrophilic and nucleophilic reactivities of the azomethine carbon of SAMP-hydrazones:: Stereoselective synthesis of γ-amino ketone derivatives
Electrophilic and nucleophilic reactivities of the azomethine carbon of SAMP-hydrazones:: Stereoselective synthesis of γ-amino ketone derivatives
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DOI：
10.1021/jo990503r
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发表时间：
1999-08-20
影响因子：
3.6
通讯作者：
Lassaletta, JM
中科院分区：
文献类型：
--
作者：
Enders, D;Díez, E;Lassaletta, JM
描述了一种不对称合成二级n - boc保护γ -氨基酮的新方法。在前手性共轭烯酮2与甲醛samp -腙1高度非对映选择性的亲核1,4加成后，生成的li-氧醛samp -腙4的羰基被保护为乙烯酮5。然后将有机金属试剂立体选择性（de 58 ~ 88%）加成到后者的CN双键上，得到的不稳定中间体肼或被捕获为moc保护的肼8，收率较高（65 ~ 87%），或被Raney镍催化的N-N键氢解还原为相应的胺，分离得到相应的N-Boc衍生物11。值得注意的是，samp -腙的亚甲基碳在这个过程中没有被本质上修饰，它依次充当亲核和亲电中心，作为共轭烯酮（亲电试剂）和有机金属试剂（亲核试剂）之间的联系，并有助于形成两个相邻的立体中心。
A novel methodology for the asymmetric synthesis of secondary N-Boc-protected gamma-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 li-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.