Stereochemical Aspects of T3P Amidations

IF 3.5 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2017-02-21 DOI:10.1021/acs.oprd.7b00046

Zheng Wang, Robert D. Barrows, Thomas J. Emge, Spencer Knapp*

引用次数: 7

Abstract

Propanephosphonic acid anhydride (T3P) is a process-friendly commercial reagent that is useful for direct carboxamide formation from the carboxylic acid and amine components. For amidation reactions of certain tetrahydroisoquinolonic carboxylic acids and electron-poor anilines, the phosphonate carboxylate mixed anhydride intermediate evidently eliminates under basic conditions to give a ketene, whose addition reaction in turn leads to a mixture of diastereomeric amide products. For example, 1,4-diazabicyclo[2,2,2]octane, used as the base, provides mostly the 3,4-cis product, whereas N-methylimidazole leads efficiently to the 3,4-trans product. A mechanistic rationale, along with compelling evidence for the intermediate ketene, is provided, as are several examples of the efficient T3P-mediated preparation of carboxamides that are of interest as active antimalarials.

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立体化学方面的T3P酰胺化

丙膦酸酐(T3P)是一种工艺友好的商业试剂，可用于从羧酸和胺组分直接生成羧胺。对于某些四氢异喹诺酮羧酸与缺电子苯胺的酰胺化反应，羧酸膦酸混合酸酐中间体在碱性条件下明显消去生成烯酮，烯酮的加成反应生成非对映体酰胺产物的混合物。例如，作为碱的1,4-重氮杂环[2,2,2]辛烷主要生成3,4-顺式产物，而n -甲基咪唑则有效地生成3,4-反式产物。本文提供了一种机制上的基本原理，以及中间体烯酮的令人信服的证据，以及几个有效的t3p介导的羧酰胺制备的例子，这些羧酰胺是有效的抗疟药。

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.