A General and Efficient Synthesis of 2‐Pyridones, 2‐Quinolinones, and 1‐Isoquinolinones from Azine N‐Oxides. Issue 12 (24th October 2016)

• Record Type: Journal Article
• Authors: Wang, Dong; Zhao, Junjie; Wang, Yuxi; Hu, Jianyong; Li, Linna; Miao, Longfei; Feng, Hairong; Désaubry, Laurent; Yu, Peng
• Is Part Of: Asian journal of organic chemistry. Volume 5:Issue 12(2016)
• Page Start: 1442
• Page End: 1446
• Publication Date: 2016-10-24
• Subjects: hydroxylation -- isotopic labeling -- nitrogen heterocycles -- N-oxides -- synthetic methods; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; 547.005
• DOI: 10.1002/ajoc.201600430
• Languages: English
• ISSNs: 2193-5807

Abstract

Abstract: 2‐Pyridones, 2‐quinolinones, and 1‐isoquinolinones are critical building blocks in medicinal chemistry. These N‐heterocycles, however, remain a challenge to synthesize by current methods. A mild, general, and efficient approach for the synthesis of these hydroxyl N‐heteroarenes was developed by employing bromotripyrrolidinophosphonium hexafluorophosphate (PyBroP) as an activating agent and sodium acetate/water as the base/nucleophile combination. The reaction mechanism, especially the dual function of sodium acetate as the base and nucleophile, has been proposed on the basis of results from isotopic labeling experiments. Abstract : N‐O Metal ! We report the synthesis of hydroxyazines under mild conditions from their N ‐oxide precursors by using bromotripyrrolidinophosphonium hexafluorophosphate (PyBroP) as an activating agent and sodium acetate/water as the base/nucleophile combination. The approach is applicable to N‐heteroarenes, such as quinolines, isoquinolines, and pyridines. A 70 % average yield among 25 successful reactions with up to a 95 % product yield was achieved. PyBroP=bromotripyrrolidinophosphonium hexafluorophosphate, DCE=1, 2‐dichloroethane.