Enamine Ltd., Chervonotkatska Street 78, Kyiv, 02094, Ukraine.
Taras Shevchenko National University of Kyiv, Volodymyrska Street 60, Kyiv, 01601, Ukraine.
Chemistry. 2022 Sep 27;28(54):e202202117. doi: 10.1002/chem.202202117. Epub 2022 Sep 2.
A scalable and efficient process for the preparation of 3-borylated pyrrolidines by 1,3-dipolar cycloaddition of N-benzyl azomethine ylide generated in situ has been developed. The optimized method included the use of LiF in DMSO at 110 °C and was suitable for α-mono-, α,β-di-, and α,β,β-trialkyl-, β,β-(hetera)cycloalkylidene-, CO Et-, as well as most β-(het)aryl-substituted alkenyl boropinacolates. The 1,3-dipolar reaction proceeded on a multigram scale providing 3-borylated pyrrolidines with diverse substitution patterns (including fused and spirocyclic ones) in a diastereoselective manner. The Pd(OH) -mediated N-debenzylation of pyrrolidine hydrochlorides was successfully performed to give the corresponding bifunctional building blocks on an up to 130 g scale, thus providing a substantial expansion of the synthetic and medicinal chemist's toolbox. Other reactions included the preparation of trifluoroborates, Zweifel-Aggarwal sp -sp coupling, and oxidative deborylation as an example of C-heteroatom bond formation.
一种通过 1,3-偶极环加成反应原位生成的 N-苄基亚甲胺叶立德制备 3-硼代吡咯烷的可扩展且高效的方法已经开发出来。优化后的方法包括在 DMSO 中使用 LiF，在 110°C 下进行反应，适用于 α-单取代、α,β-二取代和 α,β,β-三取代、β,β-（杂）环烷基亚甲胺叶立德、CO Et-取代以及大多数 β-（杂）芳基取代的烯基硼酸频哪醇酯。1,3-偶极环加成反应可以在多克规模上进行，以非对映选择性的方式提供具有多种取代模式（包括稠合和螺环）的 3-硼代吡咯烷。通过 Pd(OH) -介导的吡咯烷盐酸盐的 N-去苄基化反应成功地进行，在高达 130g 的规模上得到了相应的双功能构建块，从而为合成和药物化学家的工具包提供了实质性的扩展。其他反应包括三氟硼酸盐的制备、Zweifel-Aggarwal sp -sp 偶联以及作为 C-杂原子键形成的示例的氧化脱硼反应。
