Practical Access to Metallo Thiophenes: Regioselective Synthesis of 2,4-Disubstituted Thiophenes

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2010-10-13 DOI:10.1021/op100226k

Sylvie M. Asselin*, Matthew M. Bio, Neil F. Langille*, Ka Yi Ngai

引用次数: 8

Abstract

This report describes a protocol for functionalization of thiophenes, utilizing a regioselective magnesiation mediated by commercial Grignard reagents and catalytic 2,2,6,6-tetramethylpiperidine. This metalation provides practical access to metallo thiophenes, avoiding cryogenic conditions, prolonged reaction times, and prohibitively expensive reagents. Application to a target thiophene-phthalazinone 6 was accomplished by addition of 2-magnesio-4-methylthiophene to phthalic anhydride, providing the product with >40:1 regioselectivity. This also solved a chemoselectivity issue encountered with analogous lithio-thiophene reagents and cyclic anhydrides, or with magnesio-thiophene generated by simultaneous lithium-to-magnesium transmetalation/anhydride acylation. These alternative in situ transmetalation sequences were plagued by an age effect dictated by the kinetic solubility of MgCl₂/THF complexes.

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金属噻吩的实际获取:2,4-二取代噻吩的区域选择性合成

本报告描述了噻吩功能化的方案，利用商业格氏试剂和催化2,2,6,6-四甲基哌啶介导的区域选择性镁化。这种金属化提供了获得金属噻吩的实际途径，避免了低温条件、延长的反应时间和昂贵的试剂。将2-镁-4-甲基噻吩添加到邻苯二酸酐中，使产物具有40:1的区域选择性，从而实现了目标噻吩-酞嗪酮6的应用。这也解决了类似的锂-噻吩试剂和环酸酐，或同时由锂-镁转金属/酸酐酰化生成的镁-噻吩所遇到的化学选择性问题。这些替代的原位转金属序列受到MgCl2/THF配合物动力学溶解度所决定的年龄效应的困扰。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.