Practical and stereoselective electrocatalytic 1,2-diamination of alkenes

1,2-二胺结构广泛存在于天然产物、药物和不对称合成中使用的催化剂中。烯烃双胺化，即在烯烃两端同时引入两个氨基，是合成1,2-二胺最为简便和高效的方法之一。但该方法面临着诸多挑战，是有机合成中有待解决的难题。其难点主要是源于二胺产物对过渡金属催化剂的抑制作用以及难以控制反应非对映选择性和区域选择性。徐海超课题组对电化学促进的烯烃双官能团化反应进行了深入研究，通过进一步脱除磺酰基成功实现了高非对映选择性和区域选择性的烯烃双胺化反应，为1,2-二胺类化合物提供高效、简便的合成方法。该工作通过有机电子转移催化剂与电的结合避免了过渡金属催化剂和氧化剂的使用，且增强了底物和官能团的兼容性。 该项研究实验部分主要由博士生蔡晨燕完成，研究助理束晓敏参与了部分化合物的合成。The 1,2-diamine motif is widely present in natural products, pharmaceutical compounds, and catalysts used in asymmetric synthesis. The simultaneous introduction of two amino groups across an alkene feedstock is an appealing yet challenging approach for the synthesis of 1,2-diamines, primarily due to the inhibitory effect of the diamine products to transition metal catalysts and the difficulty in controlling reaction diastereoselectivity and regioselectivity. Herein we report a scalable electrocatalytic 1,2-diamination reaction that can be used to convert stable, easily available aryl alkenes and sulfamides to 1,2-diamines with excellent diastereoselectivity. Monosubstituted sulfamides react in a regioselective manner to afford 1,2-diamines bearing different substituents on the two amino groups. The combination of an organic redox catalyst and electricity not only obviates the use of any transition metal catalyst and oxidizing reagent, but also ensures broad reaction compatibility with a variety of electronically and sterically diverse substrates.We acknowledge the financial support of this research from MOST (2016YFA0204100), NSFC (No. 21672178), Program for Changjiang Scholars and Innovative Research Team in University and Fundamental Research Funds for the Central Universities. 研究工作得到国家重点研发计划纳米科技重点专项、国家自然科学基金、长江学者和创新团队发展计划、中央高校基本科研业务费专项资金的资助

Asymmetric benzylic C(sp3)−H acylation via dual nickel and photoredox catalysis

This work is dedicated to 100th anniversary of Xiamen University and its Chemistry.手性α-芳基酮，是一个非常重要的药效官能团，广泛存在于药物分子中，虽然含有α-季碳手性中心的芳基酮的不对称合成已经有较多报道，但是相应的具有α-叔碳手性中心的芳基酮的高效不对称合成依然极具挑战性，因为相对活泼的叔碳手性中心很容易发生外消旋化。霍浩华教授课题组在前期工作的基础上（JACS, 2020, 142, 19058.），经过一系列探索，成功将“溴自由基介导的C-H活化策略”由α-氨基sp3 C-H键拓展至苄位sp3 C-H键，在镍和光的协同催化下，实现了首例不对称苄位C(sp3)-H的酰基化反应。该研究工作在霍浩华教授指导下完成，博士研究生环磊桃和束晓敏为该论文的共同第一作者，博士研究生祖维赛和硕士研究生钟德参与了部分研究工作。Asymmetric C(sp3)−H functionalization is a persistent challenge in organic synthesis. Here, we report an asymmetric benzylic C−H acylation of alkylarenes employing carboxylic acids as acyl surrogates for the synthesis of α-aryl ketones via nickel and photoredox dual catalysis. This mild yet straightforward protocol transforms a diverse array of feedstock carboxylic acids and simple alkyl benzenes into highly valuable α-aryl ketones with high enantioselectivities. The utility of this method is showcased in the gram-scale synthesis and late-stage modification of medicinally relevant molecules. Mechanistic studies suggest a photocatalytically generated bromine radical can perform benzylic C−H cleavage to activate alkylarenes as nucleophilic coupling partners which can then engage in a nickel-catalyzed asymmetric acyl cross-coupling reaction. This bromine-radical-mediated C−H activation strategy can be also applied to the enantioselective coupling of alkylarenes with chloroformate for the synthesis of chiral α-aryl esters.We are grateful for financial support from the NSFC (22071203) and the Xiamen University. We thank professor Hai-Chao Xu (Xiamen University) for assistance and helpful discussions. We acknowledge Wesley Harrison (UIUC) for manuscript revision.研究工作得到了国家高层次青年人才项目、厦门大学南强A计划、国家自然科学基金委项目（No. 22071203）的资助