Department of Chemistry, Rutgers University , 73 Warren Street, Newark, New Jersey 07102, United States.
Org Lett. 2016 Nov 18;18(22):5872-5875. doi: 10.1021/acs.orglett.6b02952. Epub 2016 Nov 8.
A general Negishi acylation of primary amides enabled by a combination of site-selective N,N-di-Boc activation and nickel catalysis is reported for the first time. The reaction is promoted by a bench-stable, inexpensive Ni catalyst. The reaction shows excellent functional group compatibility, affording functionalized diaryl ketones by selective N-C cleavage. Most notably, this protocol represents the first amide cross-coupling by direct metal insertion of simple and readily available primary amides. The overall strategy by N,N-di-Boc activation/metal insertion is suitable for a broad range of coupling protocols via acylmetals. Mechanistic experiments suggest high reactivity of N,N-di-Boc activated 1° amides in direct amide C-N cross-couplings.
首次报道了通过 N,N-二-Boc 活化和镍催化的组合，实现伯酰胺的一般 Negishi 酰化反应。该反应由一种稳定、廉价的 Ni 催化剂促进。该反应显示出优异的官能团相容性，通过选择性 N-C 断裂得到官能化的二芳基酮。值得注意的是，该方案代表了通过简单易得的伯酰胺的直接金属插入进行酰胺交叉偶联的首例。通过 N,N-二-Boc 活化/金属插入的总体策略适用于通过酰基金属的广泛的偶联方案。机理实验表明，N,N-二-Boc 活化的 1°酰胺在直接酰胺 C-N 交叉偶联中的高反应性。
