Campbell Joseph P, Rajappan Sinu C, Jaynes Tyler J, Sharafi Mona, Ma Yong-Tao, Li Jianing, Schneebeli Severin T
Department of Chemistry, The University of Vermont, Burlington, VT, 05405, USA.
Angew Chem Int Ed Engl. 2019 Jan 21;58(4):1035-1040. doi: 10.1002/anie.201811517. Epub 2018 Dec 17.
Enantioselective electrophilic aromatic nitration methodology is needed to advance chirality-assisted synthesis (CAS). Reported here is an enantioselective aromatic nitration strategy operating with chiral diester auxiliaries, and it provides an enantioselective synthesis of a C -symmetric tribenzotriquinacene (TBTQ). These axially-chiral structures are much sought-after building blocks for CAS, but they were not accessible prior to this work in enantioenriched form without resolution of enantiomers. This nitration strategy controls the stereochemistry of threefold nitration reactions from above the aromatic rings with chiral diester arms. Dicarbonyl-to-arenium chelation rigidifies the reaction systems, so that remote stereocenters position the ester-directing groups selectively over specific atoms of the TBTQ framework. Closely guided by computational design, a more selective through-space directing arm was first predicted with density functional theory (DFT), and then confirmed in the laboratory, to outperform the initial structural design. This enantio- and regioselective TBTQ synthesis opens a new pathway to access building blocks for CAS.
对映选择性亲电芳香硝化方法对于推进手性辅助合成（CAS）至关重要。本文报道了一种使用手性二酯助剂的对映选择性芳香硝化策略，该策略实现了C对称三苯并三喹吖啶（TBTQ）的对映选择性合成。这些轴手性结构是CAS中备受追捧的结构单元，但在本工作之前，若不通过对映体拆分，就无法获得对映体富集形式的此类结构。这种硝化策略通过带有手性二酯臂的基团从芳环上方控制三重硝化反应的立体化学。二羰基与芳鎓离子的螯合作用使反应体系刚性化，从而使远程立体中心将酯导向基团选择性地定位在TBTQ骨架的特定原子上。在计算设计的紧密指导下，首先通过密度泛函理论（DFT）预测了一种更具选择性的空间导向臂，然后在实验室中得到证实，其性能优于最初的结构设计。这种对映和区域选择性的TBTQ合成开辟了一条获取CAS结构单元的新途径。
