Synthesis of an advanced precursor of Rivastigmine: Cinchona-derived quaternary ammonium salts as organocatalysts for stereoselective imine reductions

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• 作者：Andrea Genoni^a ; Maurizio Benaglia^a ; ^b ; ^{maurizio.benaglia@unimi.it" class="auth_mail" title="E-mail the corresponding author} ; Emanuele Mattiolo^a ; Sergio Rossi^a ; Laura Raimondi^a ; Pedro C. Barrulas^c ; Anthony J. Burke^c ;
• 关键词：Ketoimine reduction ; Chiral amines ; Cinchona alkaloid derivatives ; Rivastigmine ; Trichlorosilane
• 刊名：Tetrahedron Letters
• 出版年：2015
• 出版时间：14 October 2015
• 年：2015
• 卷：56
• 期：42
• 页码：5752-5756
• 全文大小：623 K

文摘

The enantioselective reduction of ketoimines has been successfully realized, using trichlorosilane as the stoichiometric reducing agent in the presence of catalytic amounts of a Lewis base, specifically a Cinchona derivative. For the first time, a novel class of derivatives was studied, featuring a picolinamide unit bound to the alkaloid scaffold, further functionalized as quaternary ammonium salt at the quinuclidine ring. Excellent yields and from good to high enantioselectivities (up to 92% ee) were obtained in the reduction of ketoimines. The novel catalysts were successfully employed in the synthesis of an enantiomerically pure advanced precursor of the blockbuster drug Rivastigmine.