Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ, 07102, USA.
Angew Chem Int Ed Engl. 2017 Oct 2;56(41):12718-12722. doi: 10.1002/anie.201707102. Epub 2017 Aug 31.
Considering the ubiquity of organophosphorus compounds in organic synthesis, pharmaceutical discovery agrochemical crop protection and materials chemistry, new methods for their construction hold particular significance. A conventional method for the synthesis of C-P bonds involves cross-coupling of aryl halides and dialkyl phosphites (the Hirao reaction). We report a catalytic deamidative phosphorylation of a wide range of amides using a palladium or nickel catalyst giving aryl phosphonates in good to excellent yields. The present method tolerates a wide range of functional groups. The reaction constitutes the first example of a transition-metal-catalyzed generation of C-P bonds from amides. This redox-neutral protocol can be combined with site-selective conventional cross-coupling for the regioselective synthesis of potential pharmacophores. Mechanistic studies suggest an oxidative addition/transmetallation pathway. In light of the importance of amides and phosphonates as synthetic intermediates, we envision that this Pd and Ni-catalyzed C-P bond forming method will find broad application.
考虑到有机合成、药物发现、农业化学作物保护和材料化学中有机磷化合物的普遍性，新的构建方法具有特殊的意义。合成 C-P 键的一种常规方法涉及芳基卤化物和二烷基膦酸酯（Hirao 反应）的交叉偶联。我们报告了使用钯或镍催化剂对广泛的酰胺进行催化脱酰胺化磷酸化，以良好至优异的收率得到芳基膦酸酯。本方法耐受多种官能团。该反应是首例通过酰胺形成 C-P 键的过渡金属催化反应。这种氧化还原中性方案可以与选择性传统交叉偶联结合使用，以进行潜在药效团的区域选择性合成。机理研究表明存在氧化加成/转金属化途径。鉴于酰胺和膦酸酯作为合成中间体的重要性，我们设想这种 Pd 和 Ni 催化的 C-P 键形成方法将得到广泛应用。
