Synthetic applications of lithiated N-Boc allylic amines as asymmetric homoenolate equivalents.
Synthetic applications of lithiated N-Boc allylic amines as asymmetric homoenolate equivalents.
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DOI：
10.1021/jo0260084
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发表时间：
2003-01
期刊：
影响因子：
--
通讯作者：
Marna C. Whisler;P. Beak
中科院分区：
文献类型：
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作者：
Marna C. Whisler;P. Beak
N-(Boc)-N-（对甲氧基苯基）烯丙基胺在(-)-sparteine存在下的锂化反应产生不对称的同烯醇酯等价物，这些等价物与亲电试剂反应产生高度富集对映体的氨基甲酸酯。烯氨基甲酸酯的酸性水解可提供相应的β -取代醛。采用立体控制的分子内硝基-烯烃偶极环加成反应，以β -烯丙基取代醛为原料制备了富集对映体的2-甲酰-4-苯基-1-氨基环戊烷。进一步的操作可以获得对映体富集的β -内酰胺。在另一个合成序列中，可以控制锂化中间体的转金属化和与醛亲电试剂的反应，以获得高度富集对映体的抗同质醇产品。在迭代反应中使用抗醛纯醛产物作为手性亲电试剂，可以得到含有四个立体中心的双纯醛产物，具有高的非对映选择性和对映选择性。提出了反应途径来解释观察到的产物。
Lithiation of N-(Boc)-N-(p-methoxyphenyl) allylic amines in the presence of (-)-sparteine provides asymmetric homoenolate equivalents which react with electrophiles to provide highly enantioenriched enecarbamates. Acidic hydrolysis of the enecarbamates can provide the corresponding beta-substituted aldehydes. A synthetic sequence that involves a stereocontrolled intramolecular nitrone-olefin dipolar cycloaddition has been developed for the preparation of enantioenriched 2-formyl-4-phenyl-1-aminocyclopentanes from one beta-allyl-substituted aldehyde. Further manipulations allow access to an enantioenriched beta-lactam. In another synthetic sequence, transmetalation of the lithiated intermediates and reactions with aldehyde electrophiles can be controlled to afford highly enantioenriched anti homoaldol products. Use of an anti aldehyde homoaldol product as the chiral electrophile in an iterative reaction provides a double homoaldol product containing four stereogenic centers with high diastereoselectivity and enantioselectivity. Reaction pathways are proposed to account for the observed products.