Gong Hegui, Gagné Michel R
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA.
J Am Chem Soc. 2008 Sep 10;130(36):12177-83. doi: 10.1021/ja8041564. Epub 2008 Aug 13.
A Ni-catalyzed Negishi cross-coupling approach to C-glycosides is described with an emphasis on C-aryl glycosides. The combination of NiCl2/PyBox in N,N'-dimethylimidazolidinone (DMI) enabled the synthesis of C-alkyl glycosides under mild reaction conditions. Moderate yields and beta-selectivities were obtained for C-glucosides, and good yields and high alpha-selectivities were the norm for C-mannosides. For C-aryl glycosides, reactions employing Ni(COD)2/(t)Bu-Terpy in N,N-dimethylformamide (DMF) were typically high yielding and provided C-glucosides with high beta-selectivities (1:>10 alpha:beta) and C-mannosides in moderate alpha-selectivities (3:1 alpha:beta); alpha-C-aryl glycosides could be obtained by the combination of Ni(COD)2/PyBox in DMF (>20:1 alpha:beta). The collective studies suggest that stereochemical control of the C-glycosides is dependent on the substrate and catalysts combination. The Negishi protocol displays excellent functional group tolerance, as demonstrated by its use in the first total synthesis of the natural product salmochelin SX.
本文描述了一种用于合成C-糖苷的镍催化的根岸交叉偶联方法，重点是C-芳基糖苷。在N，N'-二甲基咪唑啉酮（DMI）中，NiCl2/PyBox的组合能够在温和的反应条件下合成C-烷基糖苷。对于C-葡萄糖苷，可获得中等产率和β-选择性，而对于C-甘露糖苷，通常可获得良好的产率和高α-选择性。对于C-芳基糖苷，在N，N-二甲基甲酰胺（DMF）中使用Ni(COD)2/(t)Bu-Terpy的反应通常产率较高，可提供具有高β-选择性（α:β为1:>10）的C-葡萄糖苷和具有中等α-选择性（α:β为3:1）的C-甘露糖苷；通过在DMF中组合使用Ni(COD)2/PyBox（α:β>20:1）可获得α-C-芳基糖苷。这些综合研究表明，C-糖苷的立体化学控制取决于底物和催化剂的组合。根岸反应方案显示出优异的官能团耐受性，天然产物沙门菌素SX的首次全合成即证明了这一点。
