ElMarrouni Abdellatif, Ritts Casey B, Balsells Jaume
Department of Discovery Chemistry , MRL , Merck & Co., Inc. , 770 Sumneytown Pike , West Point , Pennsylvania 19486 , USA . Email:
Department of Process Research & Development , MRL , Merck & Co., Inc. , 770 Sumneytown Pike , West Point , Pennsylvania 19486 , USA . Email:
Chem Sci. 2018 Jul 11;9(32):6639-6646. doi: 10.1039/c8sc02253d. eCollection 2018 Aug 28.
The emergence of photoredox catalysis has enabled the discovery of mild and efficient conditions for the generation of a variety of radical reaction platforms. Herein is disclosed the development of a conjugate addition reaction of non-activated alkyl bromides to Michael acceptors under visible-light photoredox catalysis. Optimization of the reaction was achieved using high-throughput experimentation (HTE) tools to enable the identification of mild, general and practical reaction conditions. A diverse set of alkyl bromides was successfully added to cyclic or acyclic α,β-unsaturated esters and amides. The features of this transformation allowed also access to a key intermediate of Vorinostat®, an HDAC inhibitor used to fight cancer and HIV.
光氧化还原催化的出现使得人们能够发现温和且高效的条件来生成各种自由基反应平台。本文公开了在可见光光氧化还原催化下，未活化的烷基溴与迈克尔受体的共轭加成反应的发展。使用高通量实验（HTE）工具实现了反应的优化，从而能够确定温和、通用且实用的反应条件。多种烷基溴成功地加成到环状或非环状的α,β-不饱和酯和酰胺上。这种转化的特点还使得能够获得伏立诺他（Vorinostat®）的关键中间体，伏立诺他是一种用于对抗癌症和艾滋病的组蛋白去乙酰化酶（HDAC）抑制剂。
