A General Strategy for the Synthesis of Cyclic N-Aryl Hydroxamic Acids via Partial Nitro Group Reduction
详细信息 查看全文
- 作者：Laura A. McAllister ; Bruce M. Bechle ; Amy B. Dounay ; Edelweiss Evrard ; Xinmin Gan ; Somraj Ghosh ; Ji-Young Kim ; Vinod D. Parikh ; Jamison B. Tuttle ; Patrick R. Verhoest
- 刊名：Journal of Organic Chemistry
- 出版年：2011
- 出版时间：May 6, 2011
- 年：2011
- 卷：76
- 期：9
- 页码：3484-3497
- 全文大小：1042K
- 年卷期：v.76,no.9(May 6, 2011)
- ISSN：1520-6904
文摘
We describe a generalized approach to stereocontrolled synthesis of substituted cyclic hydroxamic acids (3-amino-1-hydroxy-3,4-dihydroquinolinones) by selective reduction of substituted 2-nitrophenylalanine substrates. Compounds in this series have antibacterial properties and have also recently been reported as KAT II inhibitors. The key nitrophenyl alanine intermediates are prepared enantioselectively in excellent yield by phase transfer catalyzed alkylation of the corresponding nitrobenzyl bromides. The scope and limitations of the reductive cyclization transformation have been explored with attention to the effects of substitution pattern and electronics on reaction efficiency and byproduct formation. In addition, a novel activated trifluoroethyl ester cyclization strategy has been developed as an alternate approach to the most sterically demanding systems in this series.