Metal-free reduction of secondary carboxylic acid amides with hydrogen

羧酸酰胺还原是叔胺和仲胺合成的关键技术。有效地访问这些非常重要的化合物类对于材料科学或药物合成中的应用是至关重要的。通常情况下，酰胺的还原是通过与络合氢化物的反应实现的，或者，在极端条件下，在过渡金属络合物和氢的存在下，通过反应来实现。然而，无金属氢气还原仲羧酸酰胺的研究尚无先例。该项目针对这一挑战开发了两个相互交织的催化循环。在三芳基氧化膦存在的情况下，仲酰胺将被三光气或三氟酸酐转化为亚胺基衍生物。反应性亚胺基衍生物在受阻路易斯对(FLP)催化下氢化生成仲胺。这一过程不仅可以获得一系列广泛的仲单胺，而且还可以从容易获得的酰胺前体中高效地合成二、三和多胺。

The reduction of carboxylic acid amides is a key technology for the synthesis of tertiary and secondary amines. The efficient access to these highly important compound classes is of utmost importance for applications in materials science or in drug synthesis. Usually the reduction of amides is achieved by the reaction with complex hydrides, or, less established, in the presence of transition metal complexes and hydrogen under drastic conditions. However, the metal-free reduction of secondary carboxylic amides by hydrogen is yet without precedence. The project targets this challenge by the development of two intertwined catalytic cycles. Secondary amides will be converted into the imidoyl derivatives by triphosgene or triflic anhydride in the presence of a triaryl phosphane oxide. The reactive imidoyl derivatives undergo frustrated Lewis pair (FLP) catalyzed hydrogenation to yield the secondary amines. This process will not only give access to a broad series of secondary monoamines but will also enable the efficient synthesis of di-, tri and polyamines from readily accessible amide precursors.