Chen Zhi, Li Yu-Fan, Tan Shun-Zhong, Ouyang Qin, Chen Zhi-Chao, Du Wei, Chen Ying-Chun
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University Chengdu 610041 China
College of Pharmacy, Third Military Medical University Shapingba Chongqing 400038 China.
Chem Sci. 2022 Oct 6;13(42):12433-12439. doi: 10.1039/d2sc05210e. eCollection 2022 Nov 2.
Although nucleophilic benzylation-type reaction to introduce various aromatic systems into molecules has been widely explored, the related pyrrolylmethylation version remains to be disclosed. Reported herein is a palladium-catalysed multiple auto-tandem reaction between Ts propargylamines, allyl carbonates and aldimines in the presence of an acid, proceeding through sequential allylic amination, cycloisomerisation, vinylogous addition and aromatisation steps. A diversity of formal pyrrolylmethylated amine products were finally furnished efficiently. In addition, switchable regiodivergent 3-pyrrolylmethylation and 4-pyrrolylmethylation were realised by tuning catalytic conditions. Moreover, remote chirality transfer with readily available enantioenriched starting materials was well achieved with an achiral ligand, relying on diastereoselective generation of η-Pd(0) complexes between Pd(0) and chiral 1,3-diene intermediates in the key vinylogous addition step. A few control experiments were conducted to elucidate the palladium-involved tandem reaction and regiodivergent synthesis.
尽管将各种芳香体系引入分子的亲核苄基化型反应已得到广泛研究，但相关的吡咯甲基化反应版本仍有待揭示。本文报道了在酸存在下，钯催化的对甲苯磺酰基炔丙胺、碳酸烯丙酯和醛亚胺之间的多重自动串联反应，该反应通过依次进行烯丙基胺化、环异构化、插烯加成和芳构化步骤进行。最终高效地得到了多种形式上的吡咯甲基化胺产物。此外，通过调节催化条件实现了可切换的区域发散性3-吡咯甲基化和4-吡咯甲基化。此外，在手性配体存在下，利用非手性配体，通过在关键的插烯加成步骤中钯(0)与手性1,3-二烯中间体之间非对映选择性地生成η-钯(0)配合物，很好地实现了从易于获得的对映体富集起始原料进行远程手性转移。进行了一些对照实验以阐明涉及钯的串联反应和区域发散性合成。
