Cu-Catalyzed Couplings of Heteroaryl Primary Amines and (Hetero)aryl Bromides with 6-Hydroxypicolinamide Ligands

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2019-07-02 DOI:10.1021/acs.oprd.9b00195

David J. Bernhardson, Daniel W. Widlicka, Robert A. Singer*

引用次数: 21

Abstract

A family of 6-hydroxypicolinamide ligands have been identified as effective supporting ligands for Cu-catalyzed couplings of heteroaryl bromides and chlorides with heteroaryl primary amines. The C–N couplings are carried out at 80–120 °C in DMSO or sulfolane using K₂CO₃ or K₃PO₄ as the base with 2–10 mol % CuI and supporting ligand. The strength of the base was found to have an impact on the chemoselectivity and rate. The use of K₂CO₃ as the base enabled selective C–N coupling of aryl bromides over aryl chlorides with 2–5 mol % Cu at 80–120 °C. With K₃PO₄ as the base, aryl chlorides are capable of undergoing C–N coupling, though 5–10 mol % Cu is required at 120–130 °C. Members of the ligand family are straightforward to prepare in one step from 6-hydroxypicolinic acid and the corresponding anilines.

Abstract Image

查看原文本刊更多论文

铜催化6-羟基喹啉酰胺配体对杂芳基伯胺和(杂)芳基溴的偶联作用

6-羟基喹啉酰胺配体家族已被确定为cu催化杂芳基溴化物和氯化物与杂芳基伯胺偶联的有效支撑配体。以K2CO3或K3PO4为碱，以2-10 mol %的CuI和配体，在80-120°C的DMSO或亚砜中进行C - n偶联。发现碱的强度对化学选择性和速率有影响。在80-120℃下，以K2CO3为碱，在2-5 mol % Cu的条件下，芳基溴与芳基氯选择性地发生了C - n偶联。以K3PO4为碱，芳基氯化物能够发生C - n偶联，尽管在120-130℃时需要5-10 mol %的Cu。配体家族的成员是直接的一步从6-羟基苯胺酸和相应的苯胺制备。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

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.