Li Can, Song Jian, Wang Ting, Fang Xianjie
Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Key Laboratory of Organosilicon Material Technology of Zhejiang Province, College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, 2318 Yuhangtang Road, Hangzhou 311121, China.
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Angew Chem Int Ed Engl. 2025 Jan 27;64(5):e202417208. doi: 10.1002/anie.202417208. Epub 2024 Nov 14.
Axially chiral nitriles are common motifs in organic photoelectric materials, biological compounds, and agrochemicals. Unfortunately, the limited synthetic approaches to axially chiral nitriles have impeded their availability. Herein, we report the first nickel-catalyzed desymmetric allylic cyanation of biaryl allylic alcohols for the synthesis of axially chiral nitrile structures in high yields with excellent enantioselectivities (up to 90 % yield and >99 % ee). This process enables the synthesis of a diverse range of axially chiral allylic nitriles bearing β,γ-unsaturated alcohol moieties. Leveraging the allylic alcohol and cyano groups as versatile functionalization handles allow for further derivatization of these axially chiral frameworks. Density functional theory (DFT) calculations suggest that both steric and electronic interactions play crucial roles in determining the enantioselectivity of this transformation. Moreover, this mild and facile protocol is also applicable for gram-scale preparation of the chiral nitriles.
轴手性腈是有机光电材料、生物化合物和农用化学品中的常见结构单元。不幸的是，轴手性腈有限的合成方法阻碍了它们的可得性。在此，我们报道了首例镍催化的联芳基烯丙醇的去对称烯丙基氰化反应，用于高产率且对映选择性优异（产率高达90%，对映体过量值>99%）地合成轴手性腈结构。该过程能够合成多种带有β,γ-不饱和醇部分的轴手性烯丙基腈。利用烯丙醇和氰基作为通用的官能化基团，可以对这些轴手性骨架进行进一步衍生化。密度泛函理论（DFT）计算表明，空间和电子相互作用在决定该转化反应的对映选择性方面都起着关键作用。此外，这种温和且简便的方法也适用于克级规模的手性腈制备。
