Enantioselective Synthesis of 3,3-Difluoropyrrolidin-4-ol, a Valuable Building Block in Medicinal Chemistry

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• 作者：Chong Si ; Kevin R. Fales ; Alicia Torrado ; Kwame Frimpong ; Talbi Kaoudi ; Harold George Vandeveer ; F. George Njoroge
• 刊名：Journal of Organic Chemistry
• 出版年：2016
• 出版时间：May 20, 2016
• 年：2016
• 卷：81
• 期：10
• 页码：4359-4363
• 全文大小：286K
• 年卷期：0
• ISSN：1520-6904

文摘

In this paper, we report for the first time two enantioselective routes to 4,4-difluoropyrrolidin-3-ol, a valuable building block in medicinal chemistry. In the first route, we took advantage of the C₂ symmetry of (3R,4R)-3,4-dihydroxypyrrolidine in which the desired chirality was derived from the chiral pool (l-(+)-tartaric acid). In the second route, we efficiently assembled the pyrrolidine ring in the presence of a gem-difluoro moiety to avoid using potentially hazardous deoxofluorinating reagents and subsequently introduced the chirality by a stereoselective iridium–diamine-catalyzed asymmetric transfer hydrogenation reaction.