An original and effective approach for achieving trifluoromethyl hydroxyalkylation of 5-phenylthiophen-2-amine using α-trifluoromethyl ketones is described. In the last few years, reaction of Friedel-Crafts had been widely used to realize hydroxyalkylation on heterocycles such as indoles or thiophenes by means of Lewis acid as catalyst. Additionally, amine functions are rarely free when carbonyl reagents are used because of their tendency to form imines. This is the first time that a site-selective electrophilic aromatic substitution on C3 atom of an unprotected 5-phenylthiophen-2-amine moiety is reported. The liberty to allow reaction in neutral conditions between free amine is valuable in a synthesis pathway. The reaction proceeds smoothly using an atom-economical metal-and catalyst-free methodology in good to excellent yields. A mechanism similar to an electrophilic aromatic substitution has been proposed.

中文翻译：

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5-苯基噻吩-2-胺与α-三氟甲基酮通过亲电芳族取代的无催化剂位点选择性羟烷基化

描述了一种使用 α-三氟甲基酮实现 5-苯基噻吩-2-胺的三氟甲基羟烷基化的原始且有效的方法。近年来，Friedel-Crafts反应被广泛用于以路易斯酸为催化剂实现吲哚、噻吩等杂环的羟烷基化反应。此外，当使用羰基试剂时，胺官能团很少游离，因为它们倾向于形成亚胺。这是首次报道未保护的 5-苯基噻吩-2-胺部分的 C3 原子上的位点选择性亲电芳族取代。允许游离胺在中性条件下反应的自由在合成途径中是有价值的。该反应使用原子经济的无金属和无催化剂方法顺利进行，产率良好。