Rhodium(III)-Catalyzed Anti-Markovnikov Hydroamidation of Unactivated Alkenes Using Dioxazolones as Amidating Reagents.

The amide is one of the most prevalent functional groups in all of pharmaceuticals and for this reason, reactions that introduce the amide moiety are of particular value. Intermolecular hydroamidation of alkenes remains an underexplored method for the synthesis of amide-containing compounds. The majority of hydroamidation procedures exhibit Markovnikov regioselectivity, while current methods for anti-Markovnikov hydroamidation are somewhat limited to activated alkene substrates or radical processes. Herein, we report a general method for the intermolecular anti-Markovnikov hydroamidation of unactivated alkenes under mild conditions, utilizing Rh(III) catalysis in conjunction with dioxazolone amidating reagents and isopropanol as an environmentally friendly hydride source. The reaction tolerates a wide range of functional groups, and efficiently converts electron-deficient alkenes, styrenes, and 1,1-disubstituted alkenes, in addition to unactivated alkenes, to their corresponding linear amides. Mechanistic studies reveal a reversible rhodium hydride migratory insertion step, leading to exquisite selectivity for the anti-Markovnikov product.

酰胺是所有药物中最常见的官能团之一，因此，引入酰胺部分的反应具有特别的价值。烯烃的分子间氢酰胺化仍然是一种用于合成含酰胺化合物的未充分探索的方法。大多数氢酰胺化过程表现出马尔科夫尼科夫区域选择性，而目前的反马尔科夫尼科夫氢酰胺化方法在一定程度上局限于活化的烯烃底物或自由基过程。在此，我们报道了一种在温和条件下对未活化烯烃进行分子间反马尔科夫尼科夫氢酰胺化的通用方法，该方法利用铑(III)催化，结合二氧杂唑酮酰胺化试剂以及异丙醇作为一种环境友好的氢化物源。该反应能耐受多种官能团，并且除了未活化烯烃外，还能有效地将缺电子烯烃、苯乙烯和1,1 - 二取代烯烃转化为它们相应的线性酰胺。机理研究揭示了一个可逆的铑氢化物迁移插入步骤，这导致了对反马尔科夫尼科夫产物的精确选择性。