Asymmetric Synthesis of N-Boc-(R)-Silaproline via Rh-Catalyzed Intramolecular Hydrosilylation of Dehydroalanine and Continuous Flow N-Alkylation

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• 作者：John Y. L. Chung ; Michael Shevlin ; Artis Klapars ; Michel Journet
• 刊名：Organic Letters
• 出版年：2016
• 出版时间：April 15, 2016
• 年：2016
• 卷：18
• 期：8
• 页码：1812-1815
• 全文大小：323K
• 年卷期：0
• ISSN：1523-7052

文摘

An asymmetric synthesis of a silicon-containing proline surrogate, N-Boc-(R)-silaproline (1), is described. Starting from N-Boc-dehydroalanine ester, deprotonation, followed by N-alkylation with chloromethyldimethylsilane under flow conditions, afforded the N-alkylated product 8 in 91% yield. An unprecedented enantioselective (NBD)₂RhBF₄/Josiphos 404-1 catalyzed 5-endo-trig hydrosilylation afforded the silaproline ester in 85–90% yield and >95% ee. Subsequent saponification and salt formation upgraded 1 to >99% ee.