Intermolecular C-H Amination of Complex Molecules: Insights into the Factors Governing the Selectivity
Intermolecular C-H Amination of Complex Molecules: Insights into the Factors Governing the Selectivity
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DOI：
10.1021/jo301563j
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发表时间：
2012-09-07
影响因子：
3.6
通讯作者：
Dauban, Philippe
中科院分区：
文献类型：
--
作者：
Lescot, Camille;Darses, Benjamin;Dauban, Philippe
过渡金属催化的 C-H 氨基化通过氮宾插入允许 C-H 直接转化为 C-N 键。鉴于有机化合物中 C-H 键的普遍存在，这样的过程引发了区域选择性和化学选择性的问题，随着底物复杂性的增加，这一具有挑战性的目标变得更加难以解决。虽然通过使用适当的系链来确保氮宾的分子内加成可以实现出色的区域控制，但分子间 C-H 胺化仍然难以预测。本研究旨在通过利用有效的立体选择性氮宾转移来解决这个问题，涉及手性胺化剂 1 与手性铑催化剂 2 的组合。由于空间和电子因素的结合，萜烯和烯醇醚的烯丙基 C-H 胺化具有优异的产率以及高区域选择性、化学选择性和非对映选择性。烯丙基 C-H 键与 pi 键的共轭可以解释观察到的环状底物的化学选择性。以化学计量使用的烷烃也可以有效地官能化，并优先使用叔平 C-H 键。在这种情况下，选择性可以通过空间效应和超共轭效应来合理化。因此，这项研究为更好地预测复杂分子的 C-H 胺化位点提供了有用的信息。
Transition-metal-catalyzed C-H amination via nitrene insertion allows the direct transformation of a C-H into a C-N bond. Given the ubiquity of C-H bonds in organic compounds, such a process raises the problem of regio- and chemoselectivity, a challenging goal even more difficult to tackle as the complexity of the substrate increases. Whereas excellent regiocontrol can be achieved by the use of an appropriate tether securing intramolecular addition of the nitrene, the intermolecular C-H amination remains much less predictable. This study aims at addressing this issue by capitalizing on an efficient stereoselective nitrene transfer involving the combination of a chiral aminating agent 1 with a chiral rhodium catalyst 2. Allylic C-H amination of terpenes and enol ethers occurs with excellent yields as well as with high regio-, chemo-, and diastereoselectivity as a result of the combination of steric and electronic factors. Conjugation of allylic C-H bonds with the pi-bond would explain the chemoselectivity observed for cyclic substrates. Alkanes used in stoichiometric amounts are also efficiently functionalized with a net preference for tertiary equatorial C-H bonds. The selectivity, in this case, can be rationalized by steric and hyperconjugative effects. This study, therefore, provides useful information to better predict the site of C-H amination of complex molecules.