Ethyl Nitroacetate in Aza-Henry Addition on Trifluoromethyl Aldimines: A Solvent-Free Procedure To Obtain Chiral Trifluoromethyl α,β-Diamino Esters

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• 作者：Luca Parise ; Alessia Pelagalli ; Lucio Pellacani ; Fabio Sciubba ; Maria Cecilia Vergari ; Stefania Fioravanti
• 刊名：Journal of Organic Chemistry
• 出版年：2016
• 出版时间：April 1, 2016
• 年：2016
• 卷：81
• 期：7
• 页码：2864-2874
• 全文大小：540K
• ISSN：1520-6904

文摘

A self-catalyzed aza-Henry addition of ethyl nitroacetate on N-alkyl trifluoromethyl aldimines was reported to synthesize β-amino α-nitro trifluoromethyl esters, precursors of α,β-diamino acid derivatives. In the presence of a resident chiral center on the imine nitrogen, the use of a suitable Lewis acid leads to a good stereofacial control, always resulting from a nucleophilic unlike attack. By starting from optically pure N-protected trifluoromethyl aldimines or directly from N-α-amino ester trifluoromethyl aldimines, small ψ[CH(CF₃)NH]-peptidomimetic backbones can be achieved in which a new primary amine function represents a possible center for synthetic extension. Finally, a very interesting, and never observed before, palladium-catalyzed syn β-elimination occurred, leading to the selective nitro group reduction reaction on the syn-α-amino ester functionalized aza-Henry adducts and obtaining more stable optically pure trifluoromethyl conjugated imines.