Late-Stage Intermolecular Allylic C–H Amination

• Published in: Journal of the American Chemical Society 2021-09, Vol.143 (37), p.14969-14975
• Main Authors: Ide, Takafumi, Feng, Kaibo, Dixon, Charlie F, Teng, Dawei, Clark, Joseph R, Han, Wei, Wendell, Chloe I, Koch, Vanessa, White, M. Christina
• Format: Article
• Language: English
• Subjects: Amination; Amines - chemical synthesis; Amines - chemistry; Catalysis; Coordination Complexes - chemistry; Molecular Structure
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.1c06335

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, [MnIII(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 [MnIII(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.