Wang Le, Wang Cheng-Long, Li Zi-Hao, Lian Peng-Fei, Kang Jun-Chen, Zhou Jia, Hao Yu, Liu Ru-Xin, Bai He-Yuan, Zhang Shu-Yu
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, & Key Laboratory of Green and High-End Utilization of Salt Lake Resources, Shanghai Jiao Tong University, Shanghai, 200240, PR China.
Nat Commun. 2024 Feb 19;15(1):1483. doi: 10.1038/s41467-024-45875-y.
Aliphatic allylic amines are common in natural products and pharmaceuticals. The oxidative intermolecular amination of C(sp)-H bonds represents one of the most straightforward strategies to construct these motifs. However, the utilization of widely internal alkenes with amines in this transformation remains a synthetic challenge due to the inefficient coordination of metals to internal alkenes and excessive coordination with aliphatic and aromatic amines, resulting in decreasing the reactivity of the catalyst. Here, we present a regioselective Cu-catalyzed oxidative allylic C(sp)-H amination of internal olefins with azodiformates to these problems. A removable bidentate directing group is used to control the regiochemistry and stabilize the π-allyl-metal intermediate. Noteworthy is the dual role of azodiformates as both a nitrogen source and an electrophilic oxidant for the allylic C-H activation. This protocol features simple conditions, remarkable scope and functional group tolerance as evidenced by >40 examples and exhibits high regioselectivity and excellent E/Z selectivity.
脂肪族烯丙基胺在天然产物和药物中很常见。C(sp³)-H键的氧化分子间胺化是构建这些结构单元最直接的策略之一。然而，由于金属与内烯烃的配位效率低下以及与脂肪族和芳香族胺的过度配位，导致催化剂活性降低，在这种转化中使用广泛的内烯烃与胺仍然是一个合成挑战。在此，我们提出了一种区域选择性铜催化的内烯烃与偶氮二甲酸酯的氧化烯丙基C(sp³)-H胺化反应来解决这些问题。使用一个可去除的双齿导向基团来控制区域化学并稳定π-烯丙基金属中间体。值得注意的是，偶氮二甲酸酯作为氮源和亲电氧化剂在烯丙基C-H活化中具有双重作用。该方法具有简单的条件、显著的底物范围和官能团耐受性，超过40个例子证明了这一点，并且具有高区域选择性和优异的E/Z选择性。
