Iridium-Catalyzed Direct Ortho-C–H Amidation of α-Ketoesters with Sulfonyl Azides Using a Transient Directing Group Strategy

Abstract

Direct C−H amidation of α-ketoesters was accomplished using various organic azides as the amino source through the combination of transient directing group strategy and iridium catalysis. Excellent functional group tolerance and wide substrate scope were explored under simple and mild conditions. Importantly, it was found that the steric hindrance of the ester moiety played a pivotal role for the reaction efficacy. In addition, the reaction could be enlarged to gram scale, and several useful heterocycles were readily constructed via one-step late-stage derivatization.

C−H Functionalization of Aldehydes and Ketones with Transient Directing Groups: Recent Developments

“…[37,38] Very recently, the same group achieved an iridium-catalyzed amidation reaction with sulfonyl azides as nitrogen source (Scheme 19.d). [39] The synthesized amido-esters 69 could be converted in one step into complex heterocycles such as isatin 70 or 1,2-dihydroquinoline 71.…”

Recent advances in metal directed C–H amidation/amination using sulfonyl azides and phosphoryl azides

“…Notably, iridium catalysts have demonstrated effectiveness in the direct C–H amination of unactivated arenes using phosphoryl azides as nitrogen sources. 32–36 In summary, the choice of a metal catalyst for directed C–H amination depends on various factors, including the substrate, the desired product, and the reaction conditions. To gain a better understanding of metal-mediated C–H activation chemistry, it is essential to establish precise definitions for key terms commonly encountered in this field before delving deeper into the discussion.…”

“…In a latest 2023 publication, Y. He et al 141 introduced an innovative method for the direct C–H amidation of α-ketoesters. This approach harnessed diverse organic azides as the amino source, utilizing a combination of a transient directing group strategy and iridium catalysis.…”