铜催化自由基介导的不对称氰基化反应研究进展

Recent advances in copper-catalyzed radical-mediated enantioselective cyanation reactions

手性腈类化合物不仅广泛存在于具有生物活性的天然产物和药物分子中,也是有机合成中一类非常重要的结构单元.因此,发展不对称催化的方法来高立体选择地构建含氰基取代的手性中心具有十分重要的研究价值和意义.合成腈类化合物传统常用的方法主要集中在亲电加成反应和烯烃的氢氰化反应等,所用的氰基化试剂毒性较大,反应条件较为苛刻.相较于这些策略,基于无毒安全的氰基化试剂,并利用过渡金属催化和自由基反应策略来构建手性腈类化合物在选择性控制和反应效率等方面无疑具有明显的优势.本综述根据自由基的类型和产生来源,对铜催化自由基介导的不对称氰基化反应进行了简要总结和分析,并对该领域的发展方向进行了展望.

Chiral nitriles are not only widely present in numerous biologically active natural products,drugs,and pharmaceuticals,but also represent a versatile class of synthetic building blocks in organic synthesis.Therefore,it is of great significance to develop highly catalytic enantioselective methods to construct structurally diverse cyano-containing com-pounds.The traditional methods are mainly focused on electrophilic addition and alkene hydrocyanation reactions,wherein toxic cyanation reagents or harsh reaction conditions are typically used.Compared with these methods,merger of transition metal catalysis and the radical chemistry has recently emerged as a powerful platform for construction of a variety of enantioenriched cyano-containing compounds under mild conditions.This strategy has obvious advantages in terms of selectivity control and reaction efficiency.This review briefly summarizes the recent advances of copper-catalyzed radical-mediated asymmetric cyanation reactions according to the types and sources of radicals.Thus far,three major strategies of copper-catalyzed radical-mediated enantioselective cyanation have been achieved,including these cyanation reactions at the relatively stabilized benzylic,propargylic,and allylic positions.In the introduction section,the significance of cyano-containing natural products and pharmaceuticals,as well as the fundamental working hypothesis of copper-catalyzed enantioselective radical cyanation are briefly discussed.In the section of benzylic radical-based asymmetric cyanations,the representative advances are discussed according to the methods employed for benzylic radical generation under thermal or light irradiation conditions.On the other hand,the propargylic radical-mediated enantioselective cyanation by dual photoredox and copper catalysis has also recently been emerging.Some recent examples in this area are thus been described.Copper-catalyzed nitrogen radical-mediated allylic C—H bond cyanation also provides a potentially robust tool for site-specific incorporation of cyano group into the allylic position.Moreover,the highly reactive sp^(3)-hybridized carbon-centered radicals,formed by addition of functionalized carbon-radicals to the unactivated alkenes could also undergo enantioselective cyanation.Despite the fairly recent emergence of these areas,the substrate scope of radical precursors is still quite limited.It is hoped that the review will provide guidelines for the design and development of new radical precursors that are suitable for copper-catalyzed asymmetric cyanation.