Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, USA.
Org Biomol Chem. 2020 May 27;18(20):3827-3831. doi: 10.1039/d0ob00813c.
A highly efficient method for chemoselective synthesis of biaryl ketones by arylation of Weinreb amides (N-methoxy-N-methylamides) with functionalized Grignard reagents is reported. This protocol offers rapid entry to functionalized biaryl ketones after Mg/halide exchange with i-PrMgCl·LiCl under operationally-simple and practical reaction conditions. The scope of the method is highlighted in >40 examples, including bioactive compounds and pharmaceutical derivatives. Collectively, this transition-metal-free approach offers a major advantage over the recently established cross-coupling of amides by oxidative addition of N-C(O) bonds. Considering the utility of amide acylation reactions in modern synthesis, we expect that this method will be of broad interest.
本文报道了一种通过 Weinerb 酰胺（N-甲氧基-N-甲基酰胺）与功能化格氏试剂的芳基化反应，高效合成联芳基酮的方法。该方法在操作简单、实用的反应条件下，通过 Mg/卤化物交换，用 i-PrMgCl·LiCl 处理后，快速得到功能化的联芳基酮。该方法的适用范围在 40 多个实例中得到了突出展示，包括生物活性化合物和药物衍生物。总的来说，这种无过渡金属的方法比最近通过 N-C（O）键的氧化加成建立的酰胺交叉偶联方法具有显著优势。考虑到酰胺酰化反应在现代合成中的实用性，我们预计这种方法将具有广泛的应用前景。
