Intermolecular C–H Amination of Complex Molecules: Insights into the Factors Governing the Selectivity

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 π-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.

通过过渡金属催化的碳-氢氮化反应，可实现碳-氢键向碳-氮键的直接转化。鉴于碳-氢键在有机化合物中的普遍存在，此类过程引发了区域选择性和化学选择性问题，而随着底物复杂性的增加，这一问题愈发棘手。尽管通过合适的连接基团确保分子内亚胺的加成，可以实现优异的区域控制，但分子间碳-氢氮化反应的预测性仍相对较低。本研究旨在通过利用高效的立体选择性亚胺转移，结合手性氨基化试剂1与手性钌催化剂2，来解决这个问题。烯丙基碳-氢氮化反应在萜烯和烯醇醚中表现出优异的产率和高度的区域、化学以及非对映选择性，这得益于立体和电子因素的协同作用。烯丙基碳-氢键与π键的共轭可解释在环状底物中观察到的化学选择性。在等摩尔量下使用的烷烃也通过高效的功能化反应得到，对三级赤道碳-氢键的偏好性显著。在这种情况下，选择性可以通过立体和超共轭效应进行合理化。因此，本研究为预测复杂分子中碳-氢氮化反应的位置提供了有价值的信息。