Preparation and Reactions of Enantiomerically Pure 伪-Functionalized Grignard Reagents

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• 作者：Peter J. Rayner ; Peter O鈥橞rien ; Richard A. J. Horan
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：May 29, 2013
• 年：2013
• 卷：135
• 期：21
• 页码：8071-8077
• 全文大小：500K
• 年卷期：v.135,no.21(May 29, 2013)
• ISSN：1520-5126

文摘

A strategy for the generation of enantiomerically pure 伪-functionalized chiral Grignard reagents is presented. The approach involves the synthesis of 伪-alkoxy and 伪-amino sulfoxides in 鈮?9:1 dr and 鈮?9:1 er via asymmetric deprotonation (s-BuLi/chiral diamine) and trapping with Andersen鈥檚 sulfinate (menthol derived). Subsequent sulfoxide 鈫?Mg exchange (room temperature, 1 min) and electrophilic trapping delivers a range of enantiomerically pure 伪-alkoxy and 伪-amino substituted products. Using this approach, either enantiomer of products can be accessed in 99:1 er from asymmetric deprotonation protocols without the use of (鈭?-sparteine as the chiral ligand. Two additional discoveries are noteworthy: (i) for the deprotonation and trapping with Andersen鈥檚 sulfinate, there is a lack of stereospecificity at sulfur due to attack of a lithiated intermediate onto the 伪-alkoxy and 伪-amino sulfoxides as they form, and (ii) the 伪-alkoxy-substituted Grignard reagent is configurationally stable at room temperature for 30 min.