Metal-free reduction of secondary carboxylic acid amides with hydrogen

羧酸酰胺的还原是合成叔胺和仲胺的关键技术。有效获得这些非常重要的化合物类别对于材料科学或药物合成中的应用至关重要。通常，酰胺的还原是通过与络合物的反应来实现的，或者，较少建立，在过渡金属络合物和氢气的存在下，在剧烈的条件下。然而，仲羧酰胺通过氢的无金属还原仍然没有先例。该项目通过开发两个相互交织的催化循环来应对这一挑战。在三芳基氧化膦存在下，仲酰胺将被三光气或三氟甲磺酸酐转化为亚氨酰衍生物。反应性亚氨酰基衍生物经历受抑的刘易斯对（FLP）催化氢化以产生仲胺。该方法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有效合成二胺、三胺和多胺。

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.