通过钯催化芳基溴的烷氧基羰基化制备活性酯的通用方法。

General method for the preparation of active esters by palladium-catalyzed alkoxycarbonylation of aryl bromides.

作者信息

de Almeida Angelina M, Andersen Thomas L, Lindhardt Anders T, de Almeida Mauro V, Skrydstrup Troels

机构信息

The Center for Insoluble Protein Structures (inSPIN), Department of Chemistry and the Interdisciplinary Nanoscience Center, Aarhus University , Gustav Wieds Vej 14, 8000 Aarhus, Denmark.

出版信息

J Org Chem. 2015 Feb 6;80(3):1920-8. doi: 10.1021/jo5025464. Epub 2015 Jan 21.

DOI:10.1021/jo5025464

PMID:25565181

Abstract

A useful method was developed for the synthesis of active esters by palladium-catalyzed alkoxycarbonylation of (hetero)aromatic bromides. The protocol was general for a range of oxygen nucleophiles including N-hydroxysuccinimide (NHS), pentafluorophenol (PFP), hexafluoroisopropyl alcohol (HFP), 4-nitrophenol, and N-hydroxyphthalimide. A high functional group tolerance was displayed, and several active esters were prepared with good to excellent isolated yields. The protocol was extended to access an important synthetic precursor to the HIV-protease inhibitor, saquinavir, by formation of an NHS ester followed by acyl substitution.

摘要

开发了一种通过钯催化（杂）芳族溴化物的烷氧基羰基化反应合成活性酯的有用方法。该方案适用于一系列氧亲核试剂，包括N-羟基琥珀酰亚胺（NHS）、五氟苯酚（PFP）、六氟异丙醇（HFP）、4-硝基苯酚和N-羟基邻苯二甲酰亚胺。该反应表现出对官能团的高耐受性，并且制备了几种活性酯，分离产率良好至优异。该方案通过形成NHS酯然后进行酰基取代，扩展到获得HIV蛋白酶抑制剂沙奎那韦的重要合成前体。