2,5-Dihydro-1H-pyrrol-3-yl Boronic Derivatives: Multigram Synthesis and Coupling Reactions,Organic Process Research & Development

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2,5-Dihydro-1H-pyrrol-3-yl Boronic Derivatives: Multigram Synthesis and Coupling Reactions
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2024-03-13 , DOI: 10.1021/acs.oprd.3c00454
Oleksandr S. Liashuk _{1,

2} , Oleksandr P. Demchuk _{1,

3} , Oleksandr V. Hryshchuk _{1,

2} , Oleksandr O. Grygorenko _{1,

2}

Affiliation

A protocol for the multigram synthesis of 3-substituted 2,5-dihydro-1H-pyrrole boronic derivatives is reported. The method relied on the triflation of N-Boc-3-oxopyrrolidine and subsequent palladium-catalyzed borylation. Optimization studies demonstrated the high efficiency of t-BuOK as a base for the triflation step and good performance of the one-pot protocol as compared with the conventional step-by-step synthesis. The method allowed the production of up to 60 g of the target compound (as pure trifluoroborate or technical-grade boropinacolate) in one run using commercially available reagents and common laboratory equipment. Application of the obtained building block for the preparation of compounds relevant to medicinal chemistry through C–C coupling reactions is also illustrated. It is suggested that the boropinacolate form of the title building block is advantageous when immediate synthesis of the coupling products is envisaged, whereas trifluoroborate is more convenient for storage and commercialization.

中文翻译：

2,5-二氢-1H-吡咯-3-基硼衍生物：多克合成和偶联反应

报道了3-取代 2,5-二氢-1 H-吡咯硼衍生物的多克合成方案。该方法依赖于N -Boc-3-氧代吡咯烷的三氟甲磺酸化和随后的钯催化硼化。优化研究表明，与传统的分步合成相比， t -BuOK 作为三氟甲磺酸基化步骤的基础具有高效性，并且一锅法具有良好的性能。该方法使用市售试剂和普通实验室设备，一次可生产多达 60 克目标化合物（纯三氟硼酸盐或工业级硼频那醇）。还说明了所获得的结构单元在通过 C-C 偶联反应制备与药物化学相关的化合物中的应用。建议当设想立即合成偶联产物时，标题结构单元的硼频那醇形式是有利的，而三氟硼酸盐更便于储存和商业化。

更新日期：2024-03-13

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