Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ, 07102, USA.
Chemistry. 2020 Jan 13;26(3):611-615. doi: 10.1002/chem.201904678. Epub 2019 Dec 16.
The direct transition-metal-free acylation of amides with functionalized Grignard reagents by highly chemoselective N-C cleavage under kinetic control has been accomplished. The method offers rapid and convergent access to functionalized biaryl ketones through transient tetrahedral intermediates. The direct access to functionalized Grignard reagents by in situ halogen-magnesium exchange promoted by the versatile turbo-Grignard reagent (iPrMgCl⋅LiCl) permits excellent substrate scope with respect to both the amide and Grignard coupling partners. These reactions enable facile, operationally simple and chemoselective access to tetrahedral intermediates from amides under significantly milder conditions than chelation-controlled intermediates. This novel direct two-component coupling sets the stage for using amides as acylating reagents in an alternative paradigm to the metal-chelated approach, acyl metals and Weinreb amides.
酰胺与功能化格氏试剂的直接过渡金属催化酰化反应在动力学控制下通过高度选择性的 N-C 键断裂得以实现。该方法通过瞬态四面体中间体快速、收敛地构建功能化联芳基酮。通过多功能 turbo-Grignard 试剂 (iPrMgCl⋅LiCl) 原位卤化镁交换直接获得功能化格氏试剂，使得酰胺和格氏试剂偶联伙伴都具有优异的底物范围。这些反应在比螯合控制中间体更温和的条件下，使酰胺容易、操作简单且选择性地得到四面体中间体。这种新颖的直接两步偶联为酰胺作为酰化试剂在金属螯合方法、酰基金属和 Weinreb 酰胺的替代范例中提供了可能性。
