2-Ethoxy-3-pyridylboronic acid: A versatile reagent for the synthesis of highly-functionalised 3-aryl/heteroaryl-pyridines via Suzuki cross-coupling reactions

摘要

This paper describes the commercially-viable synthesis and isolation of 2-ethoxy-3-pyridylboronic acid on a ca. 70 g scale via a directed ortho-metalation reaction on readily-available 2-ethoxypyridine. A range of efficient cross-coupling reactions of 2-ethoxy-3-pyridylboronic acid with selected aryl/heteroaryl halides under palladium-catalysed Suzuki-Miyaura conditions yield novel 2-ethoxy-3-aryl/heteroaryl-pyridines in high yield (heteroaryl=pyridyl, pyrimidyl, pyrazyl). The X-ray crystal structure of 2-ethoxy-3-pyridylboronic acid reveals that the boronic acid group takes part in an intramolecular O-(HO)-O-... bond with the adjacent ethoxy substituent, and an intermolecular O-(HN)-N-... bond. (c) 2005 Elsevier Ltd. All rights reserved.