Department of Chemistry, Roger Adams Laboratory, University of Illinois, 505 South Mathews Avenue, Urbana, Illinois 61801, United States.
J Am Chem Soc. 2021 Sep 22;143(37):14969-14975. doi: 10.1021/jacs.1c06335. Epub 2021 Sep 13.
Allylic amination enables late-stage functionalization of natural products where allylic C-H bonds are abundant and introduction of nitrogen may alter biological profiles. Despite advances, intermolecular allylic amination remains a challenging problem due to reactivity and selectivity issues that often mandate excess substrate, furnish product mixtures, and render important classes of olefins (for example, functionalized cyclic) not viable substrates. Here we report that a sustainable manganese perchlorophthalocyanine catalyst, [Mn(ClPc)], achieves selective, preparative intermolecular allylic C-H amination of 32 cyclic and linear compounds, including ones housing basic amines and competing sites for allylic, ethereal, and benzylic amination. Mechanistic studies support that the high selectivity of [Mn(ClPc)] may be attributed to its electrophilic, bulky nature and stepwise amination mechanism. Late-stage amination is demonstrated on five distinct classes of natural products, generally with >20:1 site-, regio-, and diastereoselectivity.
烯丙基胺化能够实现天然产物的晚期功能化，因为烯丙基 C-H 键丰富，并且氮的引入可能会改变生物特征。尽管已经取得了进展，但由于反应性和选择性问题，分子间烯丙基胺化仍然是一个具有挑战性的问题，这些问题通常需要过量的底物，提供产物混合物，并使重要类别的烯烃（例如，功能化的环状）成为不可行的底物。在这里，我们报告说，一种可持续的锰过氯酞菁催化剂 [Mn(ClPc)] 可以实现 32 种环状和线状化合物的选择性、制备性的分子间烯丙基 C-H 胺化，包括含有碱性胺和烯丙基、醚和苄基胺化竞争位点的化合物。机理研究支持 [Mn(ClPc)] 的高选择性可能归因于其亲电性、大体积性质和逐步胺化机理。在五类不同的天然产物上进行了晚期胺化，通常具有 >20:1 的位点、区域和非对映选择性。
