Palladium-catalysed C-H activation of aliphatic amines to give strained nitrogen heterocycles
Palladium-catalysed C-H activation of aliphatic amines to give strained nitrogen heterocycles
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DOI：
10.1038/nature13389
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发表时间：
2014-06-05
期刊：
影响因子：
64.8
通讯作者：
Gaunt, Matthew J.
中科院分区：
文献类型：
--
作者：
McNally, Andrew;Haffemayer, Benjamin;Gaunt, Matthew J.
基于非活化C-H键催化功能化的新化学转化的发展有可能极大地简化复杂分子的合成。过渡金属催化已经成为将这些非活性键转化为碳-碳和碳-杂原子键的有力工具（1-6），但脂肪族碳氢键的选择性转化仍然是一个挑战。最成功的方法包括一个“导向基团”，它将金属催化剂定位在特定的碳氢键附近，从而通过环金属化实现碳氢功能化(7)。大多数定向脂肪族C-H活化过程是通过一个五元环环金属化中间体进行的（8-10）。考虑到从这些中间体中产生的新反应的数量，似乎有可能确定不同的环金属化途径将导致其他有用的化学转化的发展（11）。在这里，我们报告了钯催化的C-H键激活模式，通过四元环环钯化途径进行。这里所描述的化学导致甲基的选择性转化，是一个无保护的仲胺相邻成一个合成通用的氮杂环。通过C-H胺化和羰基化过程的发展，这种以前未知的键断开的范围得到了强调，导致了氮嘧啶和β -内酰胺的合成（分别），并且暗示了一个通用的C-H功能化平台，可以简化脂肪族仲胺的合成，一类小分子是许多药物的特别重要的特征。
The development of new chemical transformations based on catalytic functionalization of unactivated C-H bonds has the potential to simplify the synthesis of complex molecules dramatically. Transition metal catalysis has emerged as a powerful tool with which to convert these unreactive bonds into carbon-carbon and carbon-heteroatom bonds(1-6), but the selective transformation of aliphatic C-H bonds is still a challenge. The most successful approaches involve a 'directing group', which positions the metal catalyst near a particular C-H bond, so that the C-H functionalization step occurs via cyclometallation(7). Most directed aliphatic C-H activation processes proceed through a five-membered-ring cyclometallated intermediate(8-10). Considering the number of new reactions that have arisen from such intermediates, it seems likely that identification of distinct cyclometallation pathways would lead to the development of other useful chemical transformations(11). Here we report a palladium-catalysed C-H bond activation mode that proceeds through a four-membered-ring cyclopalladation pathway. The chemistry described here leads to the selective transformation of a methyl group that is adjacent to an unprotected secondary amine into a synthetically versatile nitrogen heterocycle. The scope of this previously unknown bond disconnection is highlighted through the development of C-H amination and carbonylation processes, leading to the synthesis of aziridines and beta-lactams (respectively), and is suggestive of a generic C-H functionalization platform that could simplify the synthesis of aliphatic secondary amines, a class of small molecules that are particularly important features of many pharmaceutical agents.