Department of Chemistry, National University of Singapore, 12 Science Drive 2, Singapore 117549, Republic of Singapore.
School of Chemistry and Chemical Engineering, Chongqing Key Laboratory of Theoretical and Computational Chemistry, Chongqing University, Chongqing 400030, China.
J Am Chem Soc. 2020 Dec 23;142(51):21410-21419. doi: 10.1021/jacs.0c09922. Epub 2020 Dec 11.
Multicomponent catalytic processes that can generate multiple C(sp)-C(sp) bonds in a single step under mild conditions, particularly those that employ inexpensive catalysts and substrates, are highly sought-after in chemistry research for complex molecule synthesis. Here, we disclose an efficient Ni-catalyzed reductive protocol that chemoselectively merges alkenyl amides with two different aliphatic electrophiles. Starting materials are readily accessible from stable and abundant feedstock, and products are furnished in up to >98:2 regioisomeric ratios. The present strategy eliminates the use of sensitive organometallic reagents, tolerates a wide array of complex functionalities, and enables regiodivergent addition of two primary alkyl groups bearing similar electronic and steric attributes across aliphatic C═C bonds with exquisite control of site selectivity. Utility is underscored by the concise synthesis of bioactive compounds and postreaction functionalizations leading to structurally diverse scaffolds. DFT studies revealed that the regiochemical outcome originates from the orthogonal reactivity and chemoselectivity profiles of in situ generated organonickel species.
多组分催化过程能够在温和条件下一步生成多个 C(sp)-C(sp) 键，对于复杂分子合成的化学研究来说，特别需要寻找能够使用廉价催化剂和底物的方法。在这里，我们公开了一种有效的 Ni 催化还原方案，该方案能够选择性地将烯基酰胺与两种不同的脂肪族亲电试剂合并。起始原料可从稳定且丰富的原料中获得，产物的区域异构体比率高达>98:2。本策略消除了对敏感有机金属试剂的使用，可耐受广泛的复杂官能团，并且能够在脂肪族 C═C 键上以极好的区域选择性控制对具有相似电子和空间位阻属性的两个伯烷基的区域发散加成。通过简洁的生物活性化合物合成和反应后的官能化，得到结构多样的支架，突出了其实用性。DFT 研究表明，区域化学产物来源于原位生成的有机镍物种的正交反应性和化学选择性。
