Nickel-Catalyzed Enantioselective α-Alkenylation of N-Sulfonyl Amines: Modular Access to Chiral α-Branched Amines

Abstract

Chiral α-branched amines are common structural motifs in functional materials, pharmaceuticals, and chiral catalysts. Therefore, developing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein, we describe an atom-economical, modular method for a nickel-catalyzed enantioselective α-alkenylation of readily available linear N-sulfonyl amines with alkynes to afford a wide variety of allylic amines without the need for exogenous oxidants, reductants, or activating reagents. The method provides a platform for constructing chiral α-branched amines as well as derivatives such as α-amino amides and β-amino alcohols, which can be conveniently accessed from the newly introduced alkene. Given the generality, versatility, and high atom economy of this method, we anticipate that it will have broad synthetic utility.

Ni-catalyzed hydroalkylation of olefins with N-sulfonyl amines

“…On the basis of the aforementioned experiments and previous studies [49][50][51]54,56,57 , we proposed the mechanism outlined in Fig. 8.…”

“…After trying a number of weak inorganic bases (Fig. 2a), including NaOAc and K 3 PO 4 , which are crucial in our previous studies 57 , we only detect a trace amount of the desired hydroalkylation product 3a together with a side-product allylic amine 3a' by 1 H NMR spectroscopy. However, we found strong bases could dramatically promote the designed reaction profile, as well as suppress the competitive pathway that leads to 3a'.…”

“…1c). Although the Ni-catalyzed alkenylation reaction between alkynes and amines has been reported 57,58 , the above-described strategy poses a significant challenge in the form of competitive hydride elimination from one of the β-positions relative to the nickel atom (b to c vs b to side product). For instance, the alkenylation reactions between olefins and imines established by Zhou's group provided unsaturated products, allylic amines 54 .…”

External-Ligand-Free, Nickel-Catalyzed Alkenylation of N-Sulfonylamines with Internal Alkynes

“…1 H NMR (500 MHz, CDCl 3 ):  = 2.25 (s, 3 H), 2.51 (s, 6 H), 4.91 (d, J = 6.6 Hz, 1 H), 5.30 (d, J = 6.6 Hz, 1 H), 6.48 (s, 1 H), 6.47-6.77 (t, J = 7.5 Hz, 4 H), 6.86 (s, 2 H), 6.92-6.94 (m, 2 H), 7.05-7.06 (m, 4 H), 7.13-7.16 (m, 2 H), 7.20-7.26 (m, 2 H). 13 C NMR (126 MHz, CDCl 3 ):  = 20. 9, 23.1, 63.8, 114.4 (d, J = 22.4 Hz), 114.8 (d, J = 21.2 Hz), 123.1 (d, J = 2.9 Hz), 127.2, 127.…”

Nickel-Catalyzed Hydroalkylation of Terminal Olefins with Linear N-Sulfonyl Amines

“…受到镍参与的亚胺与不饱和碳碳键的氧化环金 属化历程构建亚胺的烯基化产物的启发 [6] , 他们设想, 可以利用具有 α-碳氢的磺酰胺同时作为氢源和亚胺前 体, 来实现烯烃对饱和脂肪胺的 α-碳氢插入, 这样就可 以避免烯烃的氢烷基化反应过程中使用额外的氢源 (Scheme 1b). 虽然南开大学叶萌春团队 [7] /北京大学余 志祥团队 [7] 和石航团队 [8] 在机理研究过程中, 石航团队 [5] 首先通过控制实验 和氘代实验, 验证了之前利用 N-磺酰胺作为氢烷基化 中氢源的设计. 随后对碱和硼试剂的作用进行了研究, 通过对反应试剂的不同组合后的样品进行 11 B NMR 测 试, 作者发现苯硼酸、叔丁醇钾和磺酰胺在反应体系中 会形成磺酰胺的硼酸盐化合物 e, 该化合物也经核磁共 振谱和硼元素分析鉴定.…”