Department of Chemistry, University of Minnesota-Twin Cities, 207 Pleasant Sreet SE, Minneapolis, MN, 55455, USA.
Angew Chem Int Ed Engl. 2018 May 22;57(21):6090-6094. doi: 10.1002/anie.201800595. Epub 2018 Apr 25.
Trimethylsilyl (TMS)-protected alkynes served as selective alkyne cross-coupling partners in titanium-catalyzed [2+2+1] pyrrole synthesis. Reactions of TMS-protected alkynes with internal alkynes and azobenzene under the catalysis of titanium imido complexes yielded pentasubstituted 2-TMS-pyrroles with greater than 90 % selectivity over the other nine possible pyrrole products. The steric and electronic effects of the TMS group were both identified to play key roles in this highly selective pyrrole synthesis. This strategy provides a convenient method to synthesize multisubstituted pyrroles as well as an entry point for further pyrrole diversification through facile modification of the resulting 2-silyl pyrrole products, as demonstrated through a short formal synthesis of the marine natural product lamellarin R.
三甲基硅基（TMS）保护的炔烃可用作钛催化的[2+2+1]吡咯合成中的选择性炔烃偶联伙伴。在钛亚胺配合物的催化下，TMS 保护的炔烃与内部炔烃和偶氮苯反应，生成五取代的 2-TMS-吡咯，相对于其他九种可能的吡咯产物，选择性大于 90%。TMS 基团的空间和电子效应都被确定在这种高度选择性的吡咯合成中起着关键作用。该策略为合成多取代吡咯提供了一种便捷的方法，并且通过对生成的 2-硅基吡咯产物进行简单修饰，为进一步的吡咯多样化提供了一个切入点，通过短程形式合成海洋天然产物 lamellarin R 证明了这一点。
