Fully substituted carbon centers by diastereoselective spirocyclization: stereoselective synthesis of (+)-lepadiformine C.
Fully substituted carbon centers by diastereoselective spirocyclization: stereoselective synthesis of (+)-lepadiformine C.
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DOI：
10.1021/ja104250b
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发表时间：
2010-07-21
影响因子：
15
通讯作者：
Rychnovsky, Scott D.
中科院分区：
文献类型：
--
作者：
Perry, Matthew A.;Morin, Matthew D.;Slafer, Brian W.;Wolckenhauer, Scott A.;Rychnovsky, Scott D.
N-Boc α-氨基腈的还原锂化以出乎意料的选择性生成α-氨基烷基锂试剂。中间自由基倾向于与氮孤对电子对对齐，这种相互作用导致A1，3-应变效应，使自由基的构象发生偏差。在具有α-取代基的环己烷环中，还原锂化的净效应是构型反转。在一个拴系的亲电试剂的存在下，烷基锂环化产生一个螺环化合物，再次与反转的配置。总体结果是在环化反应中保留构型。发现α-氧烷基锂环化具有相同的总体选择性，但在这种情况下，两个步骤都进行保留。这种差异可以通过仔细考虑中间几何形状来解释。利用α-氨基螺环化反应合成了Lepadiformine C。
Reductive lithiation of N-Boc α-amino nitriles generated α-amino alkyllithium reagents with unexpected selectivity. The intermediate radical prefers to align with the nitrogen lone pair, and this interaction leads to an A1,3-strain effect that biases the conformation of the radical. In cyclohexane rings with α-substituents the net effect is an inversion of configuration on reductive lithiation. In the presence of a tethered electrophile the alkyllithium cyclizes to produce a spiro compound, again with inversion of configuration. The overall result is retention of configuration in the cyclization reaction. The same overall selectivity is found with α-oxygen alkyllithium cyclizations, but in this case both steps proceed with retention. The difference can be explained by careful consideration of the intermediate geometries. The α-amino spirocyclization was utilized in a concise and stereoselective synthesis of lepadiformine C.
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