Departamento de Química Orgánica I, Universidad del País Vasco , Manuel Lardizábal 3, 20018-San Sebastián, Spain.
J Am Chem Soc. 2016 Mar 16;138(10):3282-5. doi: 10.1021/jacs.5b13385. Epub 2016 Mar 7.
A simple, new strategy for the direct asymmetric α-functionalization of 2-alkyl azaarenes is described. Specifically, a Brønsted base catalyzed conjugate addition of substituted 2-cyanomethylpyridine (and pyrazine) N-oxides to acrylate equivalents to afford hitherto elusive 2-tert-alkyl azaaryl adducts with high enantioselectivity (up to 94% ee) is realized. Extension of the method to the α-amination reaction by using azodicarboxylate esters as electrophiles is also demonstrated. Key for success is the N-oxide functionality of substrates that acts as a removable activating and stereodirecting group. A bifunctional Brønsted base catalyst bearing a squaramide with an attached bulky silyl group is also disclosed.
一种简单的、新的策略被用来直接不对称地α-官能化 2-烷基氮杂芳烃。具体来说，通过布朗斯特碱催化取代的 2-氰甲基吡啶（和吡嗪）N-氧化物与丙烯酸盐的共轭加成，以高对映选择性（高达 94%ee）得到迄今难以获得的 2-叔-烷基氮杂芳基加合物。该方法也通过使用偶氮二甲酸酯作为亲电试剂扩展到α-胺化反应。成功的关键是底物的 N-氧化物官能团，它作为一种可去除的活化和立体定向基团。还公开了一种带有手性取代的硅基的双功能布朗斯特碱催化剂。
