过渡金属催化的对映选择性C-H官能化策略彻底改变了天然产物合成的逻辑。然而,以前的应用严重依赖于贵金属催化剂的使用,例如铑和钯。在此,我们报道了在更可持续且更便宜的3d金属催化剂乙酸钴(II)的催化下,通过吡啶甲酰胺与炔烃的对映选择性C-H/N-H环化,有效合成了C 1 -手性1,2-二氢异喹啉(DHIQ)四水合物。以良好的收率和优异的对映选择性(高达 98% 收率和 >99% ee)获得了各种对映体富集的 DHIQ。该方法的稳健性和合成潜力通过几种四氢异喹啉生物碱的模块化和不对称合成得到了证明,这些生物碱包括( S )-降劳丹苷、( S )-劳丹苷、( S )-木洛匹宁、( S )-sebiferine和( S ) -cryptostyline II,以及 (+)-solifenacin、FR115427 和 (+)-NPS R-568 关键中间体的不对称合成。
Palladium-Catalyzed α-Arylation of Aryl Nitromethanes
摘要:
Catalytic conditions for the alpha-arylation of aryl nitromethanes have been discovered using parallel microscale experimentation, despite two prior reports of the lack of reactivity of these aryl nitromethane precursors. The method efficiently provides a variety of substituted, isolable diaryl nitromethanes. In addition, it is possible to sequentially append two different aryl groups to nitromethane. Mild oxidation conditions were identified to afford the corresponding benzophenones via the Nef reaction, and reduction conditions were optimized to afford several diaryl methylamines.
作者:Yves Dejaegher、Sven Mangelinckx、Norbert De Kimpe
DOI:10.1055/s-2002-19328
日期:——
The synthesis of para di- and monosubstituted benzhydrylamines by addition of Grignard reagents to benzonitriles and subsequent reduction, is evaluated and discussed. The reduction step with sodium borohydride allows simple handling and mild conditions. An optimized synthesis of 4,4'-dimethoxybenzhydrylamine by this method is disclosed.
The present invention relates to substituted 4-hydroxypyrimidine-5-carboxamides useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.
Benzimidazole derivatives, which are useful as TIE-2 and/or VEGFR2 inhibitors are described herein. The described invention also includes methods of making such benzimidazole derivatives as well as methods of using the same in the treatment of hyperproliferative diseases.